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MannKind’s Afrezza Has Mega-Blockbuster Potential
by: KLLJ Investments December 13, 2010 | about: MNKD Font Size: PrintEmail Recommend 0 Share this page
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article to Biotech investors are always looking for the next big drug that will become a mega-blockbuster. Human Genome Sciences (HGSI) continues to receive a high valuation because of the prospects for Benlysta, which will be the first new therapy to treat Lupus in 50 years. Their market cap is close to $5B, with Benlysta expected to do around $1.5B a year -- split 50/50 with GlaxoSmithKline (GSK) -- in 2015 and approval isn't even in hand yet. Dendreon (DNDN) is valued at over $5B and Provenge is forecasted to do about the same in revenue, $1.5B in 2015. Lupus and Cancer are hot therapies for biotechs.
Who cares about a better insulin? Insulin isn’t sexy and exciting on the surface -- it has been used to treat diabetes for 90 years. Pfizer’s (PFE) Exubera was supposed to change all of that with an inhaleable form of insulin and it was forecasted to do $2B a year in annual sales. Instead it was an utter failure and now nobody cares about inhaleable insulin, less alone a better insulin. It is yesterday’s news I guess.
In my last article on MannKind’s (MKND) Afrezza, I tried to address why the street and bear analysts are completely wrong when it comes to Afrezza’s potential and the comparison to Exubera is like comparing a Yugo to a Gulfstream. In this continuation article, I discuss the keys to unlocking Afrezza’s multi-billion dollar potential.
In a report released in late November by national healthcare insurance giant, UnitedHealth Group (UNH), they estimate that more than half of America will be a diabetic or pre-diabetic by the end of the next decade at a cost of $3.35 trillion to our healthcare system. According to a recent report from the CDC, a child born today has a one in three chance of becoming a diabetic in a few decades if things don’t change in our country and we could wind up with as many as 500M type 2 diabetics worldwide at the current rate of expansion. Outside of obesity, there is no bigger cost to the world’s healthcare system.
Insulin, even though it has been around for almost a century, is still the best treatment for type 2 diabetics that can’t control the disease through lifestyle modification and metformin alone. Type 1 diabetics don’t have choice but to take insulin but they make up only 5% or so of the overall population of diabetics. Insulin lowers HbA1c better than any form of therapy but it is often a treatment of last resort when it comes to type 2 diabetes. Why? Because there are a number of barriers for introducing insulin that keep it on the back burner for as long as possible. Overcoming these obstacles is the first key to unlocking Afrezza’s potential. Even with these massive roadblocks, insulin is already a $10B product worldwide and growing year over year.
In an article published by Irl Hirsch, M.D. (University of Washington School of Medicine) in 2005 entitled “Optimal Initiation of Insulin in Type 2 Diabetes,” Dr. Hirsch writes about the impact insulin therapy can have on Type 2 Diabetics and the optimal initiation plan to use insulin. Dr. Hirsch states that “it can be anticipated that most patients will eventually require insulin therapy to achieve and maintain glycemic control.” Regarding the ADA’s goal of maintaining a HbA1c < 6.5%, “Such stringent levels of glucose control cannot generally be maintained with oral antidiabetic drugs alone (OADs). However, overall rates of insulin use for Type 2 diabetes in the United States are very low. Approximately 11% of patients are treated with a combination of insulin plus OADs and another 16% receive insulin monotherapy. An A1C < 7.0% is only achieved in 36% of patients.”
Hirsch goes on to describe the barriers to initiating insulin therapy:
“Delays in initiating insulin may stem from both physician and patient barriers. Negative patient perceptions regarding insulin include fear of injections and hypoglycemia. In some cases, patients may perceive insulin as a sign of their personal failure to control the disease. Clinician concerns include hypoglycemia, weight gain, and the misconception that elevated insulin increases cardiovascular risks. In addition, both clinicians and patients may consider insulin therapy to be complicated and labor-intensive.”
Let’s look at how Afrezza addresses each of the barriers to insulin therapy:
Fear of Injections: This is the most common reason cited for delaying insulin therapy. Nobody wants to take a shot, especially not 4 times a day. Under the current standard of care, Basal insulin -- i.e. Sanofi Aventis’ (SNY) Lantus -- is typically introduced to patients starting insulin therapy before Prandial mealtime insulin -- i.e. Eli Lilly’s (LLY) Lispro. The reason being is one shot a day is easier to convince a patient to take than three or four mealtime injections. This completely changes with Afrezza. Afrezza opens up the door for physicians to start insulin far earlier in the treatment plan than has ever been done before, which will expand the market size. Ironically, this was the main benefit for Exubera and why their sales were expected to be over $2B a year. However, Exubera had a terrible device design and also failed to address the remaining barriers to entry. Even though Exubera didn't have a good device and no clinical benefit over injected insulin, the patients that did try it, actually loved it.
Weight Gain: Unlike existing insulin options, Afrezza does not result in weight gain. The label should say that Afrezza is weight neutral or at a minimum, that it causes less weight gain than rapid-acting analogs.
Fear of Hypoglycemia: Hypoglycemia is the number 1 side effect of insulin therapy. This happens when there is too much insulin in the body, resulting in low blood sugar. This is why titrating the proper dose of insulin is so important with injected insulin. Hypoglycemia can be mild, just causing you to feel bad but sometimes can be severe, resulting in a coma or even death. With Afrezza, this risk is greatly reduced compared to injected insulin. The risk of severe hypos is reduced by an impressive 63%. This is a direct result of the ultra-fast action of Afrezza resulting in peak insulin levels at 14min, which quickly leaves the body – similar to a normal person’s insulin response to a meal. This is a far contrast to the current gold standard mealtime insulin products that peak at 52min and Exubera, which peaked at 49min.
Insulin is Complicated to Dose and Manage: This is the final barrier to overcome and it will take a good education / sales program to effectively address it. Overtime, as physicians become more comfortable, it will no longer be an issue. With Afrezza, the dosing is very simple and typically, you would use the same dosage before every meal. This means there is very little titration that needs to happen before a meal – just basic carbohydrate estimates. It also means there won’t be a need for rigorous self-monitoring of blood glucose. Afrezza’s simplicity and elegance will greatly ease the overhead typically associated with insulin therapy. Overcoming this barrier quickly will be influenced greatly by the next key to unlocking Afrezza’s potential.
A good partner is the final key for unleashing Afrezza’s multi-billion dollar potential. This will also be the largest catalyst to the stock price in my opinion. MannKind needs a partner that desperately needs to expand their diabetes program. A company like Merck (MRK) or AstraZeneca (AZN) would be a great fit. Whoever the partner is, proper execution of the marketing plan will be the key to Afrezza’s quick adoption by prescribers and patients. With the right partner in place, MannKind could rapidly reach the planned launch capacity of 400,000 patients. At $2K per patient, that equates to $800M a year in revenue. With just $100M in expansions to MannKind’s award-winning plant in Danbury, CT, capacity would go up to 2M patients or $4B in annual sales. It is also worth noting that MannKind already owns enough insulin (at a cost of $3M) to fuel the first $10B in sales. Gross margins for the initial few years on the market will be astounding.
Price Predictions: As a long-term investor, I’m more concerned about the price for MNKD 3-5 years from now as Afrezza is widely used in the US and the rest of the world, as opposed to short term price fluctuations. However, since I am frequently asked for price targets, I’ll go ahead and provide some estimates. All of the technicals for MNKD look excellent with a clear reverse head and shoulder pattern in place. The break above $7.20’s resistance on good volume indicates a possible run to $9 prior to the 12/29 PDUFA, which is also supported by the upper trendline. If this happens, approval could trigger price appreciation to the $15-20 range. However, a further delay or complete response letter would cause a major sell off but how low would depend on what was in the CRL. If it is a slight delay then perhaps back to $5, if something more onerous then it could drop to $3. Partnership is the biggest key to the price appreciation, and I believe this will happen between 2-8 weeks after approval. Once a Big Pharma has signed on to commercialize Afrezza, we will have insight into their sales guidance, which will force the Street to reevaluate revenue expectations. If the Partner guides that Afrezza is a $2-4B drug in the US, which it is, then arbitrage will take place and MNKD would be justified to have a marketcap higher than HGSI or DNDN. Something over $5B is reasonable to expect considering Afrezza’s revenue potential is more than Benlysta and Provenge combined.
However, before any of this can happen, the FDA needs to approve Afrezza. It is possible of course the bears are right and the FDA will issue another CRL. I don’t believe they will but many do and that is why the stock is less than $10. With December 29th only days away, we’ll all know soon. I for one am hoping for an early Christmas present this year.
Disclosure: I am long MNKD.
About the author: KLLJ Investments
by: KLLJ Investments December 13, 2010 | about: MNKD Font Size: PrintEmail Recommend 0 Share this page
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article to Biotech investors are always looking for the next big drug that will become a mega-blockbuster. Human Genome Sciences (HGSI) continues to receive a high valuation because of the prospects for Benlysta, which will be the first new therapy to treat Lupus in 50 years. Their market cap is close to $5B, with Benlysta expected to do around $1.5B a year -- split 50/50 with GlaxoSmithKline (GSK) -- in 2015 and approval isn't even in hand yet. Dendreon (DNDN) is valued at over $5B and Provenge is forecasted to do about the same in revenue, $1.5B in 2015. Lupus and Cancer are hot therapies for biotechs.
Who cares about a better insulin? Insulin isn’t sexy and exciting on the surface -- it has been used to treat diabetes for 90 years. Pfizer’s (PFE) Exubera was supposed to change all of that with an inhaleable form of insulin and it was forecasted to do $2B a year in annual sales. Instead it was an utter failure and now nobody cares about inhaleable insulin, less alone a better insulin. It is yesterday’s news I guess.
In my last article on MannKind’s (MKND) Afrezza, I tried to address why the street and bear analysts are completely wrong when it comes to Afrezza’s potential and the comparison to Exubera is like comparing a Yugo to a Gulfstream. In this continuation article, I discuss the keys to unlocking Afrezza’s multi-billion dollar potential.
In a report released in late November by national healthcare insurance giant, UnitedHealth Group (UNH), they estimate that more than half of America will be a diabetic or pre-diabetic by the end of the next decade at a cost of $3.35 trillion to our healthcare system. According to a recent report from the CDC, a child born today has a one in three chance of becoming a diabetic in a few decades if things don’t change in our country and we could wind up with as many as 500M type 2 diabetics worldwide at the current rate of expansion. Outside of obesity, there is no bigger cost to the world’s healthcare system.
Insulin, even though it has been around for almost a century, is still the best treatment for type 2 diabetics that can’t control the disease through lifestyle modification and metformin alone. Type 1 diabetics don’t have choice but to take insulin but they make up only 5% or so of the overall population of diabetics. Insulin lowers HbA1c better than any form of therapy but it is often a treatment of last resort when it comes to type 2 diabetes. Why? Because there are a number of barriers for introducing insulin that keep it on the back burner for as long as possible. Overcoming these obstacles is the first key to unlocking Afrezza’s potential. Even with these massive roadblocks, insulin is already a $10B product worldwide and growing year over year.
In an article published by Irl Hirsch, M.D. (University of Washington School of Medicine) in 2005 entitled “Optimal Initiation of Insulin in Type 2 Diabetes,” Dr. Hirsch writes about the impact insulin therapy can have on Type 2 Diabetics and the optimal initiation plan to use insulin. Dr. Hirsch states that “it can be anticipated that most patients will eventually require insulin therapy to achieve and maintain glycemic control.” Regarding the ADA’s goal of maintaining a HbA1c < 6.5%, “Such stringent levels of glucose control cannot generally be maintained with oral antidiabetic drugs alone (OADs). However, overall rates of insulin use for Type 2 diabetes in the United States are very low. Approximately 11% of patients are treated with a combination of insulin plus OADs and another 16% receive insulin monotherapy. An A1C < 7.0% is only achieved in 36% of patients.”
Hirsch goes on to describe the barriers to initiating insulin therapy:
“Delays in initiating insulin may stem from both physician and patient barriers. Negative patient perceptions regarding insulin include fear of injections and hypoglycemia. In some cases, patients may perceive insulin as a sign of their personal failure to control the disease. Clinician concerns include hypoglycemia, weight gain, and the misconception that elevated insulin increases cardiovascular risks. In addition, both clinicians and patients may consider insulin therapy to be complicated and labor-intensive.”
Let’s look at how Afrezza addresses each of the barriers to insulin therapy:
Fear of Injections: This is the most common reason cited for delaying insulin therapy. Nobody wants to take a shot, especially not 4 times a day. Under the current standard of care, Basal insulin -- i.e. Sanofi Aventis’ (SNY) Lantus -- is typically introduced to patients starting insulin therapy before Prandial mealtime insulin -- i.e. Eli Lilly’s (LLY) Lispro. The reason being is one shot a day is easier to convince a patient to take than three or four mealtime injections. This completely changes with Afrezza. Afrezza opens up the door for physicians to start insulin far earlier in the treatment plan than has ever been done before, which will expand the market size. Ironically, this was the main benefit for Exubera and why their sales were expected to be over $2B a year. However, Exubera had a terrible device design and also failed to address the remaining barriers to entry. Even though Exubera didn't have a good device and no clinical benefit over injected insulin, the patients that did try it, actually loved it.
Weight Gain: Unlike existing insulin options, Afrezza does not result in weight gain. The label should say that Afrezza is weight neutral or at a minimum, that it causes less weight gain than rapid-acting analogs.
Fear of Hypoglycemia: Hypoglycemia is the number 1 side effect of insulin therapy. This happens when there is too much insulin in the body, resulting in low blood sugar. This is why titrating the proper dose of insulin is so important with injected insulin. Hypoglycemia can be mild, just causing you to feel bad but sometimes can be severe, resulting in a coma or even death. With Afrezza, this risk is greatly reduced compared to injected insulin. The risk of severe hypos is reduced by an impressive 63%. This is a direct result of the ultra-fast action of Afrezza resulting in peak insulin levels at 14min, which quickly leaves the body – similar to a normal person’s insulin response to a meal. This is a far contrast to the current gold standard mealtime insulin products that peak at 52min and Exubera, which peaked at 49min.
Insulin is Complicated to Dose and Manage: This is the final barrier to overcome and it will take a good education / sales program to effectively address it. Overtime, as physicians become more comfortable, it will no longer be an issue. With Afrezza, the dosing is very simple and typically, you would use the same dosage before every meal. This means there is very little titration that needs to happen before a meal – just basic carbohydrate estimates. It also means there won’t be a need for rigorous self-monitoring of blood glucose. Afrezza’s simplicity and elegance will greatly ease the overhead typically associated with insulin therapy. Overcoming this barrier quickly will be influenced greatly by the next key to unlocking Afrezza’s potential.
A good partner is the final key for unleashing Afrezza’s multi-billion dollar potential. This will also be the largest catalyst to the stock price in my opinion. MannKind needs a partner that desperately needs to expand their diabetes program. A company like Merck (MRK) or AstraZeneca (AZN) would be a great fit. Whoever the partner is, proper execution of the marketing plan will be the key to Afrezza’s quick adoption by prescribers and patients. With the right partner in place, MannKind could rapidly reach the planned launch capacity of 400,000 patients. At $2K per patient, that equates to $800M a year in revenue. With just $100M in expansions to MannKind’s award-winning plant in Danbury, CT, capacity would go up to 2M patients or $4B in annual sales. It is also worth noting that MannKind already owns enough insulin (at a cost of $3M) to fuel the first $10B in sales. Gross margins for the initial few years on the market will be astounding.
Price Predictions: As a long-term investor, I’m more concerned about the price for MNKD 3-5 years from now as Afrezza is widely used in the US and the rest of the world, as opposed to short term price fluctuations. However, since I am frequently asked for price targets, I’ll go ahead and provide some estimates. All of the technicals for MNKD look excellent with a clear reverse head and shoulder pattern in place. The break above $7.20’s resistance on good volume indicates a possible run to $9 prior to the 12/29 PDUFA, which is also supported by the upper trendline. If this happens, approval could trigger price appreciation to the $15-20 range. However, a further delay or complete response letter would cause a major sell off but how low would depend on what was in the CRL. If it is a slight delay then perhaps back to $5, if something more onerous then it could drop to $3. Partnership is the biggest key to the price appreciation, and I believe this will happen between 2-8 weeks after approval. Once a Big Pharma has signed on to commercialize Afrezza, we will have insight into their sales guidance, which will force the Street to reevaluate revenue expectations. If the Partner guides that Afrezza is a $2-4B drug in the US, which it is, then arbitrage will take place and MNKD would be justified to have a marketcap higher than HGSI or DNDN. Something over $5B is reasonable to expect considering Afrezza’s revenue potential is more than Benlysta and Provenge combined.
However, before any of this can happen, the FDA needs to approve Afrezza. It is possible of course the bears are right and the FDA will issue another CRL. I don’t believe they will but many do and that is why the stock is less than $10. With December 29th only days away, we’ll all know soon. I for one am hoping for an early Christmas present this year.
Disclosure: I am long MNKD.
About the author: KLLJ Investments
Ich bin ja mal wirklich gespannt, was Ende Dezember passiert.
Hey, hast du gesehen, was bei Intercell passiert ist?
Ganz schön herb die Verluste, hatte noch vor ungefähr einer Woche an einen Einstieg gedacht, aber zum Glück nicht ausgeführt. Schwein gehabt...
Hey, hast du gesehen, was bei Intercell passiert ist?
Ganz schön herb die Verluste, hatte noch vor ungefähr einer Woche an einen Einstieg gedacht, aber zum Glück nicht ausgeführt. Schwein gehabt...
Servus,
ja, daß ist brutal bei den Biotechs, hopp oder topp!
Daumen drücken für MNKD!
Gruß
ja, daß ist brutal bei den Biotechs, hopp oder topp!
Daumen drücken für MNKD!
Gruß
5 Millionen Aktien von Mannkind gehandelt mit 10 % Plus und das kurz vor der Zulassung, zweite Dendreon?
Das sieht wirklich gut aus!! Muss sagen, die Aktie hatte ich völlig falsch eingeschätzt.
Aber lieber so herum, als wenn man einer Aktie hohes Potential zugesteht und dann einen Flop landet ;-)
Aber lieber so herum, als wenn man einer Aktie hohes Potential zugesteht und dann einen Flop landet ;-)
Wahnsinn, 3 Millionen Stück gehandelt in den ersten Stunden 9 US Dollar, wissen da wieder einige mehr?
Gute Zusammenfassung für die Mannkind Story, no risk no fun:
The Curious
Posted: Dec 15, 2010 10:15 AM by Stephen Simpson
Share Email AnalysisPrint
Filed Under: Fundamental Analysis,Stocks
Tickers in this Article: BIOD, MDT, MNKD, NKTR, NVO, PFE, SNY
Sometimes it is not always best to be first, sometimes it is better to let others go first and play the role on unwitting minesweeper. That is certainly what investors in MannKind (Nasdaq:MNKD) are hoping as this company approaches a critical FDA decision date (December 29) for its inhaled insulin product. While prior attempts at inhaled insulin have gone down in flames, MannKind may be in a position to learn from these mistakes and prosper where others have failed.
IN PICTURES: 9 Simple Investing Ratios You Need To Know
A Different Inhaled Insulin
There seems to be almost a knee-jerk need to compare MannKind's Afrezza (also spelled AFREZZA) to the failed inhaled insulin product developed and marketed by Pfizer (NYSE:PFE) and Nektar (Nasdaq:NKTR) known as Exubera. Exubera was a high-profile $2 billion failure for Pfizer, and this failure was followed quickly by the abandonment of inhaled insulin programs at Lilly (NYSE:LLY) and Novo Nordisk (NYSE:NVO).
Get Free Stock Analysis By Email Afrezza is a different product, though. Exubera was in most respects just an inhalable alternative to injected rapid-acting insulins like Sanofi-aventis' (NYSE:SNY) Apidra, Lilly's Humalog or Novo's NovoRapid. While these insulins have a peak of activity around 60 minutes after administration, Exubera peaked around 49 minutes. By comparison, Afrezza peaks in just 12-14 minutes, much more closely mimicking natural post-meal insulin secretion from a healthy pancreas.
Ultimately, Exubera was a pain for all involved. Insurance companies did not see why they should pay for it, doctors did not want the headache of training patients for something that offered no clinical benefit and diabetics themselves did not see any compelling reason to bother with the system. (For more, see Investing For The Diabetes Epidemic)
Can Afrezza Solve These Problems?
In its favor, MannKind's system is easier to use - it is smaller and more intuitive than Exubera's system. Moreover, inhaled insulin may be easier to administer than injections for some patients. MannKind has also wisely chosen not to pursue premium pricing for the product, suggesting it will be basically on par with rapid-acting analogs.
Afrezza also seems to be safer and to have a better side-effect profile than Exubera. There have not been the indications of lung cancer that spooked some people with Exubera, nor the same level of respiratory problems. In fact, Afrezza trials have shown a slight reduction in hypoglycemia incidents (a very serious side-effect in many diabetes treatments).
Not All Good News, Though
Unfortunately, Afrezza is not the slam-dunk its supporters want it to be. None of the clinical trials done to date have shown any superiority in efficacy (as measured by HbA1c) for inhaled insulin. In fact, every trial I have seen has shown a slight underperformance for Afrezza - not enough to be statistically significant or technically inferior, but enough to suggest that Afrezza is not demonstrably better at maintaining long-term glucose control.
Moreover, I fear that some investors may overstate the benefits of an inhaled insulin delivery system. It is true that there is substantial needle-fear in patients who are starting insulin therapy, but that fear disappears. As part of my consulting work, I have seen several surveys of diabetics (covering thousands of respondents) and there is a remarkable and consistent curve - those who have never injected are very bothered by the idea, but that fear and anxiety declines rapidly once they begin therapy and become accustomed to it. Consequently, there may not be as much commercial demand for the product as people think - particularly if doctors spend time with patients to ease their anxieties about injections. (For more, see Stocks On Drugs: What It Takes To Get High.)
The Bottom Line
It is interesting that the FDA elected not to have a panel meeting for this product. Bulls suggest that the prior approval of Exubera means one is not needed; bears say it is a sign that the FDA will reject this drug again. It is also worth noting that there is a long and inglorious history with the FDA and diabetes drugs. Novartis (NYSE:NVS) abandoned Galvus after FDA rejection, Takeda abandoned alogliptin, Biodel (Nasdaq:BIOD) saw the FDA reject Linjeta and NovoNordisk saw significant delays before getting approval for Victoza and NovoLog. With the FDA in the midst of a safety obsession and an accusation that there may have been fraud in MannKind's trials, the FDA may decide to go conservative and ask for still more data. (For more, see Dark Days In Diabetes)
It is hard to bet against Al Mann, the CEO of MannKind and founder of MiniMed (now part of Medtronic (NYSE:MDT)), and Afrezza does seem to work. With an absence of clinical superiority, though, it is equally hard to see the FDA happily signing off on a product that does not seem to address a clear need. This is a high-risk, high-potential biotech story and a severely risk-averse FDA would seem to place more of the weight on "high-risk". (For related reading, see FDA's Bizarro World - Orexigen Gets Approval!)
Use the Investopedia Stock Simulator to trade the stocks mentioned in this stock analysis, risk free!
By Stephen Simpson
Stephen Simpson, CFA, is a freelance financial writer, investor, and consultant. He has worked as an equity analyst for both sell-side and buy-side investment companies in both equities and fixed income. Stephen's consulting work has focused primarily upon the healthcare sector, while he has also written extensively for publication on topics pertaining to investments, security analysis, and healthcare. Simpson operates the Kratisto Investing blog, and can be reached there.
The Curious
Posted: Dec 15, 2010 10:15 AM by Stephen Simpson
Share Email AnalysisPrint
Filed Under: Fundamental Analysis,Stocks
Tickers in this Article: BIOD, MDT, MNKD, NKTR, NVO, PFE, SNY
Sometimes it is not always best to be first, sometimes it is better to let others go first and play the role on unwitting minesweeper. That is certainly what investors in MannKind (Nasdaq:MNKD) are hoping as this company approaches a critical FDA decision date (December 29) for its inhaled insulin product. While prior attempts at inhaled insulin have gone down in flames, MannKind may be in a position to learn from these mistakes and prosper where others have failed.
IN PICTURES: 9 Simple Investing Ratios You Need To Know
A Different Inhaled Insulin
There seems to be almost a knee-jerk need to compare MannKind's Afrezza (also spelled AFREZZA) to the failed inhaled insulin product developed and marketed by Pfizer (NYSE:PFE) and Nektar (Nasdaq:NKTR) known as Exubera. Exubera was a high-profile $2 billion failure for Pfizer, and this failure was followed quickly by the abandonment of inhaled insulin programs at Lilly (NYSE:LLY) and Novo Nordisk (NYSE:NVO).
Get Free Stock Analysis By Email Afrezza is a different product, though. Exubera was in most respects just an inhalable alternative to injected rapid-acting insulins like Sanofi-aventis' (NYSE:SNY) Apidra, Lilly's Humalog or Novo's NovoRapid. While these insulins have a peak of activity around 60 minutes after administration, Exubera peaked around 49 minutes. By comparison, Afrezza peaks in just 12-14 minutes, much more closely mimicking natural post-meal insulin secretion from a healthy pancreas.
Ultimately, Exubera was a pain for all involved. Insurance companies did not see why they should pay for it, doctors did not want the headache of training patients for something that offered no clinical benefit and diabetics themselves did not see any compelling reason to bother with the system. (For more, see Investing For The Diabetes Epidemic)
Can Afrezza Solve These Problems?
In its favor, MannKind's system is easier to use - it is smaller and more intuitive than Exubera's system. Moreover, inhaled insulin may be easier to administer than injections for some patients. MannKind has also wisely chosen not to pursue premium pricing for the product, suggesting it will be basically on par with rapid-acting analogs.
Afrezza also seems to be safer and to have a better side-effect profile than Exubera. There have not been the indications of lung cancer that spooked some people with Exubera, nor the same level of respiratory problems. In fact, Afrezza trials have shown a slight reduction in hypoglycemia incidents (a very serious side-effect in many diabetes treatments).
Not All Good News, Though
Unfortunately, Afrezza is not the slam-dunk its supporters want it to be. None of the clinical trials done to date have shown any superiority in efficacy (as measured by HbA1c) for inhaled insulin. In fact, every trial I have seen has shown a slight underperformance for Afrezza - not enough to be statistically significant or technically inferior, but enough to suggest that Afrezza is not demonstrably better at maintaining long-term glucose control.
Moreover, I fear that some investors may overstate the benefits of an inhaled insulin delivery system. It is true that there is substantial needle-fear in patients who are starting insulin therapy, but that fear disappears. As part of my consulting work, I have seen several surveys of diabetics (covering thousands of respondents) and there is a remarkable and consistent curve - those who have never injected are very bothered by the idea, but that fear and anxiety declines rapidly once they begin therapy and become accustomed to it. Consequently, there may not be as much commercial demand for the product as people think - particularly if doctors spend time with patients to ease their anxieties about injections. (For more, see Stocks On Drugs: What It Takes To Get High.)
The Bottom Line
It is interesting that the FDA elected not to have a panel meeting for this product. Bulls suggest that the prior approval of Exubera means one is not needed; bears say it is a sign that the FDA will reject this drug again. It is also worth noting that there is a long and inglorious history with the FDA and diabetes drugs. Novartis (NYSE:NVS) abandoned Galvus after FDA rejection, Takeda abandoned alogliptin, Biodel (Nasdaq:BIOD) saw the FDA reject Linjeta and NovoNordisk saw significant delays before getting approval for Victoza and NovoLog. With the FDA in the midst of a safety obsession and an accusation that there may have been fraud in MannKind's trials, the FDA may decide to go conservative and ask for still more data. (For more, see Dark Days In Diabetes)
It is hard to bet against Al Mann, the CEO of MannKind and founder of MiniMed (now part of Medtronic (NYSE:MDT)), and Afrezza does seem to work. With an absence of clinical superiority, though, it is equally hard to see the FDA happily signing off on a product that does not seem to address a clear need. This is a high-risk, high-potential biotech story and a severely risk-averse FDA would seem to place more of the weight on "high-risk". (For related reading, see FDA's Bizarro World - Orexigen Gets Approval!)
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By Stephen Simpson
Stephen Simpson, CFA, is a freelance financial writer, investor, and consultant. He has worked as an equity analyst for both sell-side and buy-side investment companies in both equities and fixed income. Stephen's consulting work has focused primarily upon the healthcare sector, while he has also written extensively for publication on topics pertaining to investments, security analysis, and healthcare. Simpson operates the Kratisto Investing blog, and can be reached there.
...no risk no fun.
Bin wirklich gespannt........hoffe, die Negativpunkte werden nicht überwiegen
Bin wirklich gespannt........hoffe, die Negativpunkte werden nicht überwiegen
Na, da geht was ab im Amiland, vorher satt rauf und jetzt bear raid und keiner weiß was los ist!
ich hege eigentlich keine besonders grossen Erwartungen an Kurssprünge direkt nach der Zulassung, da der Kurs im Dezember schon 40% zugelegt hat. Das sind schon mal eine grosse Menge Trader die sich direkt nach der Entscheidung, wie sie auch ausfällt, wieder verabschieden werden.
Von der Mehrzahl der Finanzgemeinde wird Afrezza vorerst nur als noch ein weiteres Insulinpräparat auf dem sowieso schon umkämpften Markt angesehen, und nicht als das"vermutlich bedeutsamste pharmazeutische Produkt aller Zeiten" wie Al Mann es zuweilen nennt. Das kann sich erst ändern wenn Afrezza so am Markt einschlägt wie die bereits Investierten erwarten, oder durch ein beeindruckendes Verhandlungsergebnis mit dem Big Pharmapartner. Die Vermarktung soll aber erst in der zweiten Jahreshälfte 2011 beginnen, für Interessenten also noch genug Zeit sich einzudecken.
Tatsächlich ist das Risikoverhältnis auf den ersten Blick eher ungünstig, ein kleines Aufwärtspotential nach PDUFA steht einem heftigen Abwärtspotential bei Ablehnung/neu geforderten Studien entgegen.
Wenn ich nicht so überzeugt von Afrezza wäre, wäre es das Vernünftigste gewesen, nach dem Dezemberkursanstieg zu verkaufen und nach Zulassung zu kaufen. Aktuell kommt mir aber ausser direkter Korruption bei der Behörde kein echter Grund zur Ablehnung in den Sinn. Die Shortquote ist mit 18 Millionen von 113 Mio, also ca 16% nur etwa halb so hoch wie vor dem CRL, was ich durchaus beruhigend finde, bezüglich Informationsleaks, usw. .
Von der Mehrzahl der Finanzgemeinde wird Afrezza vorerst nur als noch ein weiteres Insulinpräparat auf dem sowieso schon umkämpften Markt angesehen, und nicht als das"vermutlich bedeutsamste pharmazeutische Produkt aller Zeiten" wie Al Mann es zuweilen nennt. Das kann sich erst ändern wenn Afrezza so am Markt einschlägt wie die bereits Investierten erwarten, oder durch ein beeindruckendes Verhandlungsergebnis mit dem Big Pharmapartner. Die Vermarktung soll aber erst in der zweiten Jahreshälfte 2011 beginnen, für Interessenten also noch genug Zeit sich einzudecken.
Tatsächlich ist das Risikoverhältnis auf den ersten Blick eher ungünstig, ein kleines Aufwärtspotential nach PDUFA steht einem heftigen Abwärtspotential bei Ablehnung/neu geforderten Studien entgegen.
Wenn ich nicht so überzeugt von Afrezza wäre, wäre es das Vernünftigste gewesen, nach dem Dezemberkursanstieg zu verkaufen und nach Zulassung zu kaufen. Aktuell kommt mir aber ausser direkter Korruption bei der Behörde kein echter Grund zur Ablehnung in den Sinn. Die Shortquote ist mit 18 Millionen von 113 Mio, also ca 16% nur etwa halb so hoch wie vor dem CRL, was ich durchaus beruhigend finde, bezüglich Informationsleaks, usw. .
Also ich bin ganz Deiner Meinung bis auf die Zulassungsdynamik, bei Zulassung sehe ich zweistellige Kurse, bei Verzögerung Halbierung!
Kein CRL sondern nur 4 Wochen Verzögerung, ich glaube diesesmal wird Mannkind die Zulassung erhalten:
MannKind Updates Status of New Drug Application for AFREZZA®
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MNKD 7.97 0.00
{"s" : "mnkd","k" : "a00,a50,b00,b60,c10,g00,h00,l10,p20,t10,v00","o" : "","j" : ""} Press Release Source: MannKind Corporation On Tuesday December 28, 2010, 6:30 am
VALENCIA, Calif.--(BUSINESS WIRE)-- MannKind Corporation (Nasdaq:MNKD - News) today announced that it was informed on December 27, 2010 by the U.S. Food & Drug Administration (FDA) that the agency will not be able to complete the review of the New Drug Application (NDA) for AFREZZA® (insulin human [rDNA origin]) Inhalation Powder by the action date of December 29, 2010. The FDA stated that it will require approximately four additional weeks to complete its review of the NDA.
About AFREZZA®
AFREZZA® is a novel, ultra rapid acting mealtime insulin therapy being developed by MannKind Corporation for the treatment of adult patients with type 1 and type 2 diabetes for the control of hyperglycemia. It is a combination product, consisting of AFREZZA Inhalation Powder pre-metered into single use dose cartridges and delivered via a small, discreet and easy-to-use AFREZZA Inhaler. Administered at the start of a meal, AFREZZA dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, mimicking the early release of mealtime insulin observed in healthy individuals. To date, the AFREZZA clinical program has involved more than 50 different studies and over 5,000 adult patients with both type 1 and type 2 diabetes.
About MannKind Corporation
MannKind Corporation (Nasdaq:MNKD - News) focuses on the discovery, development and commercialization of therapeutic products for patients with diseases such as diabetes and cancer. Its diabetes pipeline includes AFREZZA® and MKC253. MannKind has submitted a NDA to the FDA requesting approval of AFREZZA for the treatment of adults with type 1 or type 2 diabetes for the control of hyperglycemia. MKC253 is currently in phase 1 clinical trials. Other products in MannKind's pipeline include the cancer immunotherapy platform MKC1106, which is currently in phase 2 clinical trials. MannKind maintains a website at www.mannkindcorp.com to which MannKind regularly posts copies of its press releases as well as additional information about MannKind. Interested persons can subscribe on the MannKind website to e-mail alerts that are sent automatically when MannKind issues press releases, files its reports with the Securities and Exchange Commission or posts certain other information to the website.
Forward Looking Statements
This press release contains forward-looking statements, including statements related to the regulatory approval process with respect to AFREZZA, that involve risks and uncertainties. Words such as “anticipates”, “intends”, “plans”, “proposes”, “expects”, “will”, and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind’s current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to difficulties or delays in seeking or obtaining regulatory approval and other risks detailed in MannKind’s filings with the Securities and Exchange Commission, including the Annual Report on Form 10-K for the year ended December 31, 2009 and periodic reports on Form 10-Q and Form 8-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and MannKind undertakes no obligation and expressly disclaims any duty to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.
Contact:
Investors:MannKind Corporation
MannKind Updates Status of New Drug Application for AFREZZA®
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MNKD 7.97 0.00
{"s" : "mnkd","k" : "a00,a50,b00,b60,c10,g00,h00,l10,p20,t10,v00","o" : "","j" : ""} Press Release Source: MannKind Corporation On Tuesday December 28, 2010, 6:30 am
VALENCIA, Calif.--(BUSINESS WIRE)-- MannKind Corporation (Nasdaq:MNKD - News) today announced that it was informed on December 27, 2010 by the U.S. Food & Drug Administration (FDA) that the agency will not be able to complete the review of the New Drug Application (NDA) for AFREZZA® (insulin human [rDNA origin]) Inhalation Powder by the action date of December 29, 2010. The FDA stated that it will require approximately four additional weeks to complete its review of the NDA.
About AFREZZA®
AFREZZA® is a novel, ultra rapid acting mealtime insulin therapy being developed by MannKind Corporation for the treatment of adult patients with type 1 and type 2 diabetes for the control of hyperglycemia. It is a combination product, consisting of AFREZZA Inhalation Powder pre-metered into single use dose cartridges and delivered via a small, discreet and easy-to-use AFREZZA Inhaler. Administered at the start of a meal, AFREZZA dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, mimicking the early release of mealtime insulin observed in healthy individuals. To date, the AFREZZA clinical program has involved more than 50 different studies and over 5,000 adult patients with both type 1 and type 2 diabetes.
About MannKind Corporation
MannKind Corporation (Nasdaq:MNKD - News) focuses on the discovery, development and commercialization of therapeutic products for patients with diseases such as diabetes and cancer. Its diabetes pipeline includes AFREZZA® and MKC253. MannKind has submitted a NDA to the FDA requesting approval of AFREZZA for the treatment of adults with type 1 or type 2 diabetes for the control of hyperglycemia. MKC253 is currently in phase 1 clinical trials. Other products in MannKind's pipeline include the cancer immunotherapy platform MKC1106, which is currently in phase 2 clinical trials. MannKind maintains a website at www.mannkindcorp.com to which MannKind regularly posts copies of its press releases as well as additional information about MannKind. Interested persons can subscribe on the MannKind website to e-mail alerts that are sent automatically when MannKind issues press releases, files its reports with the Securities and Exchange Commission or posts certain other information to the website.
Forward Looking Statements
This press release contains forward-looking statements, including statements related to the regulatory approval process with respect to AFREZZA, that involve risks and uncertainties. Words such as “anticipates”, “intends”, “plans”, “proposes”, “expects”, “will”, and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind’s current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to difficulties or delays in seeking or obtaining regulatory approval and other risks detailed in MannKind’s filings with the Securities and Exchange Commission, including the Annual Report on Form 10-K for the year ended December 31, 2009 and periodic reports on Form 10-Q and Form 8-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and MannKind undertakes no obligation and expressly disclaims any duty to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.
Contact:
Investors:MannKind Corporation
Al Mann ist zuversichtlich, ich auch: PREVIEW-MannKind awaits FDA ruling on diabetes drug Tweet This Share on LinkedIn Share on Facebook 0diggsdiggRelated NewsUPDATE 3-US rejects Teva version of MS drug, but shares up Thu, Dec 23 2010 UPDATE 3-Novo Nordisk says targets 2013 Degludec launch Thu, Dec 23 2010 UPDATE 3-Novo Nordisk, Emisphere sign insulin tablet deal Tue, Dec 21 2010 UPDATE 4-AstraZeneca stumbles as Brilinta held up in U.S. Fri, Dec 17 2010 Analysis: Pfizer investors debate shake-up, break-up Fri, Dec 17 2010Related TopicsStocks » Global Markets » Healthcare » Stocks MannKind Corporation MNKD.O $7.97 -0.15-1.85% 12:00am UTC+0100 ELI LILLY AND COMPANY LLY.N $35.07 -0.16-0.45% 12:00am UTC+0100 Novo Nordisk A/S NOVOb.CO kr.630.00 +0.00+0.00% 9:46am UTC+0100 Thu Dec 23, 2010 2:39pm EST * FDA to rule on Afrezza approval by Dec. 29 * Short interest builds up in MannKind stock * CEO Mann confident of ultimate approval By Toni Clarke BOSTON, Dec 23 (Reuters) - MannKind Corp (MNKD.O) is about to learn whether U.S. regulators will approve its experimental inhaled insulin device, Afrezza, as a treatment for diabetes. Afrezza is a whistle-sized inhaler that is designed to deliver a more effective rapid-acting insulin than injectable products such as Eli Lilly & Co's (LLY.N) Humalog and Novo Nordisk's (NOVOb.CO) NovoLog. In March, the FDA said it would not approve the device until MannKind provided more information about it. The company's shares, which had reached a year high of $11.12 in January, fell to a low of $4.76 at the end of May. Since then they have rebounded somewhat and were trading at $8.45 on Thursday on Nasdaq. The Valencia, California-based company believes it has provided the agency with what it needs, but expectations for the product's approval on Wall Street are not high. As of Nov. 30, roughly 24 percent of the company's regularly traded shares were held "short" by investors betting that the stock will fall. The FDA is expected to make its decision by Dec. 29. "We continue to think that Afrezza will again be delayed by the FDA and that the recent price appreciation creates an opportunity ahead of what we think will be a major negative catalyst for the stock," said Jon LeCroy, an analyst at Hapoalim Securities. Investor skepticism is due in part to failed attempts by much bigger drugmakers -- particularly Pfizer Inc (PFE.N) -- to develop inhaled insulin. Pfizer's inhaled insulin device, Exubera, was approved in 2006 and had been expected to generate annual sales of $2 billion. But the inhaler was bulky and patients were put off by the need for periodic lung function tests. In the first nine months of 2007, Exubera generated just $12 million in sales. Pfizer abandoned the product. Alfred Mann, 85, the company's founder and chief executive, points to the fact that Afrezza is much smaller than Exubera, and he does not believe lung function tests are necessary. "I have no doubt that Afrezza will be approved," he said in a telephone interview from Hawaii. "Whether it happens next week is something I can't predict, but if it's not approved next week I expect it to be approved some time in 2011." Diabetes affects about 24 million children and adults in the United States. In Type 1 diabetes, the body does not produce insulin, a hormone that is needed to convert sugar into energy. People with the more common Type 2 diabetes do not produce enough insulin or cells ignore the insulin. 1 2 Next
Verdict on MNKD's Afrezza Deferred
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MNKD 8.01 -0.22
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{"s" : "mnkd,pfe","k" : "a00,a50,b00,b60,c10,g00,h00,l10,p20,t10,v00","o" : "","j" : ""} Zacks Equity Research, On Wednesday December 29, 2010, 9:45 am EST
Recently, the US Food and Drug Administration (FDA) stated that it will not be able to arrive at a decision regarding MannKind Corporation’s (NasdaqGM: MNKD - News) inhaled insulin candidate, Afrezza, by December 29, 2010 as announced previously.
The US regulatory body stated that it will need approximately 4 more weeks to complete its review of the application seeking marketing approval for Afrezza in the US. The candidate is being developed for treating type I and type II diabetes.
We remind investors that the FDA accepted MannKind’s resubmitted new drug application (NDA) in July this year after issuing a complete response letter (CRL) to MannKind on Afrezza in March 2010 due to insufficiency of data. While issuing the CRL, the agency asked for information about the commercial version of the company’s MedTone inhaler, which is different from the one used during clinical trials. Furthermore, the FDA requested for updated safety data.
The resubmitted NDA, in response to the CRL, included safety and efficacy data from the completed studies on the candidate. The resubmission was classified as a Class II review. Consequently, a decision from the FDA was expected to be out within 6 months and a target date of December 29, 2010 was assigned. However, the latest decision to defer the verdict by approximately 28 days implies that a final verdict should be out in January 2011.
Afrezza utilizes MannKind’s proprietary dry powder Technosphere formulation of insulin. It is inhaled deep into the lungs using the company’s MedTone inhaler. Once inside the lungs, the insulin is rapidly absorbed into the bloodstream.
Lucrative Diabetes Market
Afrezza, on approval, will target the highly lucrative diabetes market which provides one of the largest opportunities in pharmaceuticals. The market has a huge unmet need with a high incidence of diabetes. A study published by Diabetes Care in 2006 projected that about 48.3 million people would be diagnosed with diabetes in the US by 2050.
Moreover, competition in the inhaled insulin field is virtually absent now following the withdrawal of inhaled insulin candidates by big pharma companies like Pfizer (NYSE: PFE - News). The lack of competition in the inhaled insulin market will help Afrezza gain share, in our view, after approval.
We remain ‘Neutral’ on MannKind in the long-term which is supported by the Zacks #3 Rank (‘Hold’ rating) carried by the company in the short run.
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{"s" : "mnkd,pfe","k" : "a00,a50,b00,b60,c10,g00,h00,l10,p20,t10,v00","o" : "","j" : ""} Zacks Equity Research, On Wednesday December 29, 2010, 9:45 am EST
Recently, the US Food and Drug Administration (FDA) stated that it will not be able to arrive at a decision regarding MannKind Corporation’s (NasdaqGM: MNKD - News) inhaled insulin candidate, Afrezza, by December 29, 2010 as announced previously.
The US regulatory body stated that it will need approximately 4 more weeks to complete its review of the application seeking marketing approval for Afrezza in the US. The candidate is being developed for treating type I and type II diabetes.
We remind investors that the FDA accepted MannKind’s resubmitted new drug application (NDA) in July this year after issuing a complete response letter (CRL) to MannKind on Afrezza in March 2010 due to insufficiency of data. While issuing the CRL, the agency asked for information about the commercial version of the company’s MedTone inhaler, which is different from the one used during clinical trials. Furthermore, the FDA requested for updated safety data.
The resubmitted NDA, in response to the CRL, included safety and efficacy data from the completed studies on the candidate. The resubmission was classified as a Class II review. Consequently, a decision from the FDA was expected to be out within 6 months and a target date of December 29, 2010 was assigned. However, the latest decision to defer the verdict by approximately 28 days implies that a final verdict should be out in January 2011.
Afrezza utilizes MannKind’s proprietary dry powder Technosphere formulation of insulin. It is inhaled deep into the lungs using the company’s MedTone inhaler. Once inside the lungs, the insulin is rapidly absorbed into the bloodstream.
Lucrative Diabetes Market
Afrezza, on approval, will target the highly lucrative diabetes market which provides one of the largest opportunities in pharmaceuticals. The market has a huge unmet need with a high incidence of diabetes. A study published by Diabetes Care in 2006 projected that about 48.3 million people would be diagnosed with diabetes in the US by 2050.
Moreover, competition in the inhaled insulin field is virtually absent now following the withdrawal of inhaled insulin candidates by big pharma companies like Pfizer (NYSE: PFE - News). The lack of competition in the inhaled insulin market will help Afrezza gain share, in our view, after approval.
We remain ‘Neutral’ on MannKind in the long-term which is supported by the Zacks #3 Rank (‘Hold’ rating) carried by the company in the short run.
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BY KATHY SHWIFF
With biopharmaceutical company MannKind awaiting word from the Food and Drug Administration on its key product candidate, an inhalable form of insulin, Chairman and Chief Executive Alfred Mann has spent more than $22 million in recent months to add to his already considerable holdings of company shares.
Mr. Mann, the company's founder, plans to buy additional shares at prevailing market prices as part of an agreement reached with the company in August to cancel debt the company owes him.
In the past six years, Mr. Mann has purchased more than $370 million worth of company shares, according to data ...
With biopharmaceutical company MannKind awaiting word from the Food and Drug Administration on its key product candidate, an inhalable form of insulin, Chairman and Chief Executive Alfred Mann has spent more than $22 million in recent months to add to his already considerable holdings of company shares.
Mr. Mann, the company's founder, plans to buy additional shares at prevailing market prices as part of an agreement reached with the company in August to cancel debt the company owes him.
In the past six years, Mr. Mann has purchased more than $370 million worth of company shares, according to data ...
Lexicon Announces Positive Results from New Clinical Study of LX4211 in Type 2 Diabetes Patients
| Print |
LX4211 Rapidly Lowered Blood Sugar and Increased GLP-1 and PYY,
Mediators of Glycemic and Appetite Control
The Woodlands, Texas, January 6, 2011 – Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, announced data from a recently completed clinical trial and mechanistic study of a solid oral dose formulation for LX4211, a dual inhibitor of sodium-glucose co-transporters 1 and 2 (SGLT1 and SGLT2).
Results from the study demonstrated that administration of a 300 mg solid oral tablet dose of LX4211, administered as two 150 mg tablets, significantly increased total GLP-1 (p=0.001), active GLP-1 (p=0.032) and PYY (p=0.004), important mediators of glycemic and appetite control as well as other metabolic parameters. Notably, single doses of LX4211 produced rapid and significant improvement in post-prandial glucose (PPG) and fasting plasma glucose (FPG), consistent with results seen in the previous Phase 2 study. Pharmacokinetic and pharmacodynamic data from the study indicated that the solid oral formulation worked as well as or better than the liquid formulation on key parameters of hormonal release, PPG and FPG. Lexicon plans to move the tablet formulation forward into a Phase 2b study in the second quarter of 2011.
“The significant elevations of GLP-1 levels observed in the study are particularly important given its established relevance in the treatment of diabetes,” said Brian Zambrowicz, Ph.D., executive vice president and chief scientific officer. “Newly observed in this study was the effect of LX4211 on increasing circulating levels of PYY. We believe the rapid reduction in blood sugar levels after meals, the increase in GLP-1 and the increase in PYY are all associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract.”
PYY and GLP-1 are gastrointestinal-derived peptide hormones that have been associated with producing satiety and reducing food intake. PYY has been studied as an anti-obesity agent, and GLP-1 is a mediator of insulin and glucagon secretion. As nutrients enter the small intestine, PYY and GLP-1 are co-secreted into the circulation by neuroendocrine cells (L cells) of the gastrointestinal tract.
“We have established a solid tablet formulation suitable for further development and will continue to explore LX4211’s unique mechanism of action in the treatment of diabetes and the hormonal control of metabolism,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer. “We believe the results of this study provide further evidence that dual inhibition of SGLT1 and SGLT2 may provide enhanced glycemic control over SGLT2 inhibition alone, consistent with the remarkable results observed in our Phase 2a clinical trial of LX4211.”
About the Clinical Trial
The clinical trial compared a new solid oral dose formulation of LX4211 to the liquid dose formulation used in prior clinical trials of LX4211. The trial employed a randomized, triple-cross over design during which 12 patients with type 2 diabetes each received 300 mg of LX4211 in different dose forms. Patients were administered a single dose of two 150 mg tablets, six 50 mg tablets or a 300 mg liquid dose formulation in varying sequences at 5-day intervals over a total period of 15 days. Pharmacokinetic and pharmacodynamic measures were monitored at frequent time points at baseline and after administration of each of the three dose forms with baseline measures prior to dosing used as controls.
Additional details regarding the results from this latest clinical study will be presented on Monday, January 10, 2011 at the JP Morgan Healthcare Conference. A live webcast of the presentation will be available through Lexicon’s corporate website at www.lexpharma.com. An archived version of the presentation will be available for 30 days after the event.
About LX4211
LX4211 is an orally-delivered small molecule under development as a potential treatment for diabetes. LX4211 inhibits both sodium-glucose co-transporter type 1 (SGLT1) and sodium-glucose co-transporter type 2 (SGLT2). SGLT2 is a transporter responsible for most of the glucose reabsorption performed by the kidney. SGLT1 is a transporter responsible for glucose and galactose absorption in the gastrointestinal tract, and to a lesser extent than SGLT2, glucose reabsorption in the kidney. For more information on LX4211 please visit www.lexpharma.com.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon currently has four drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, and irritable bowel syndrome, all of which were discovered by Lexicon’s research team. Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs. For additional information about Lexicon and its programs, please visit www.lexpharma.com.
Safe Harbor Statement
This press release contains “forward-looking statements,” including statements relating to the characterization of the results observed in the referenced clinical trial and prior clinical trials of LX4211 as positive or remarkable, the mechanism of action of LX4211, and the potential therapeutic and commercial potential of LX4211 generally. This press release also contains forward-looking statements relating to Lexicon’s growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon’s ability to successfully conduct clinical development of LX4211 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Factors Affecting Forward-Looking Statements” and “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2009, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.
| Print |
LX4211 Rapidly Lowered Blood Sugar and Increased GLP-1 and PYY,
Mediators of Glycemic and Appetite Control
The Woodlands, Texas, January 6, 2011 – Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, announced data from a recently completed clinical trial and mechanistic study of a solid oral dose formulation for LX4211, a dual inhibitor of sodium-glucose co-transporters 1 and 2 (SGLT1 and SGLT2).
Results from the study demonstrated that administration of a 300 mg solid oral tablet dose of LX4211, administered as two 150 mg tablets, significantly increased total GLP-1 (p=0.001), active GLP-1 (p=0.032) and PYY (p=0.004), important mediators of glycemic and appetite control as well as other metabolic parameters. Notably, single doses of LX4211 produced rapid and significant improvement in post-prandial glucose (PPG) and fasting plasma glucose (FPG), consistent with results seen in the previous Phase 2 study. Pharmacokinetic and pharmacodynamic data from the study indicated that the solid oral formulation worked as well as or better than the liquid formulation on key parameters of hormonal release, PPG and FPG. Lexicon plans to move the tablet formulation forward into a Phase 2b study in the second quarter of 2011.
“The significant elevations of GLP-1 levels observed in the study are particularly important given its established relevance in the treatment of diabetes,” said Brian Zambrowicz, Ph.D., executive vice president and chief scientific officer. “Newly observed in this study was the effect of LX4211 on increasing circulating levels of PYY. We believe the rapid reduction in blood sugar levels after meals, the increase in GLP-1 and the increase in PYY are all associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract.”
PYY and GLP-1 are gastrointestinal-derived peptide hormones that have been associated with producing satiety and reducing food intake. PYY has been studied as an anti-obesity agent, and GLP-1 is a mediator of insulin and glucagon secretion. As nutrients enter the small intestine, PYY and GLP-1 are co-secreted into the circulation by neuroendocrine cells (L cells) of the gastrointestinal tract.
“We have established a solid tablet formulation suitable for further development and will continue to explore LX4211’s unique mechanism of action in the treatment of diabetes and the hormonal control of metabolism,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer. “We believe the results of this study provide further evidence that dual inhibition of SGLT1 and SGLT2 may provide enhanced glycemic control over SGLT2 inhibition alone, consistent with the remarkable results observed in our Phase 2a clinical trial of LX4211.”
About the Clinical Trial
The clinical trial compared a new solid oral dose formulation of LX4211 to the liquid dose formulation used in prior clinical trials of LX4211. The trial employed a randomized, triple-cross over design during which 12 patients with type 2 diabetes each received 300 mg of LX4211 in different dose forms. Patients were administered a single dose of two 150 mg tablets, six 50 mg tablets or a 300 mg liquid dose formulation in varying sequences at 5-day intervals over a total period of 15 days. Pharmacokinetic and pharmacodynamic measures were monitored at frequent time points at baseline and after administration of each of the three dose forms with baseline measures prior to dosing used as controls.
Additional details regarding the results from this latest clinical study will be presented on Monday, January 10, 2011 at the JP Morgan Healthcare Conference. A live webcast of the presentation will be available through Lexicon’s corporate website at www.lexpharma.com. An archived version of the presentation will be available for 30 days after the event.
About LX4211
LX4211 is an orally-delivered small molecule under development as a potential treatment for diabetes. LX4211 inhibits both sodium-glucose co-transporter type 1 (SGLT1) and sodium-glucose co-transporter type 2 (SGLT2). SGLT2 is a transporter responsible for most of the glucose reabsorption performed by the kidney. SGLT1 is a transporter responsible for glucose and galactose absorption in the gastrointestinal tract, and to a lesser extent than SGLT2, glucose reabsorption in the kidney. For more information on LX4211 please visit www.lexpharma.com.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon currently has four drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, and irritable bowel syndrome, all of which were discovered by Lexicon’s research team. Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs. For additional information about Lexicon and its programs, please visit www.lexpharma.com.
Safe Harbor Statement
This press release contains “forward-looking statements,” including statements relating to the characterization of the results observed in the referenced clinical trial and prior clinical trials of LX4211 as positive or remarkable, the mechanism of action of LX4211, and the potential therapeutic and commercial potential of LX4211 generally. This press release also contains forward-looking statements relating to Lexicon’s growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon’s ability to successfully conduct clinical development of LX4211 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Factors Affecting Forward-Looking Statements” and “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2009, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.
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What Does a Delay Mean for Eventual Approval? An Analysis
By Rockford Coscia, on January 5th, 2011
Recently, MannKind’s (MNKD) Afrezza NDA decision was delayed for ‘approximately four weeks’ with no reason given. The market responded positively, sending MNKD share prices up over 8% on the news, before eventually settling back into its pre-announcement trading range. But what does the delay actually mean for MannKind? And what about the delay for Human Genome Sciences’ Benlysta? Is there actually a trend between delays and the eventual outcome of the decision?
Some articles have hastily cobbled together some statistics about delays but unfortunately have fallen short of offering a real analysis. I therefore wanted to take a in-depth look at several NDA action date (aka PDUFA date) delays to dig up some data that might be actionable.
First let’s collect the data. Here is a run-down of several NDA action date delays, along with the reasons for the delay and the ultimate decision by the FDA. I’ve tried to be as comprehensive as possible, but if I’ve missed something please mention it in the comments and we’ll update our data. While the analysis is post-hoc and hardly statistically significant, it should be enough for us to establish some trends pertaining to the aforementioned delays.
Spectrum Pharmaceuticals (SPPI) - Levoleucovorin (calcium leucovorin, pure isomer) NDA for adjuvant for methotrexate
Original PDUFA date: Jan 11, 2008
Extension date: Mar 7, 2008
Reason: No reason given
Result: Approval – Mar 7, 2008
Adolor (ADLR)/GlaxoSmithKline (GSK) – ENTEREG (alvimopan) for the management of postoperative ileus (POI)
Original PDUFA date: Feb 10, 2008
1st Extension date: May 10, 2008
Reason: A REMS program was submitted and led to a three month extension (although not explicitly stated as the reason).
2nd Extension date: The FDA did not provide a specific date, but informed the company that it expects to issue the action letter shortly after the scheduled PDUFA date
Result: Approval – May 20, 2008
Daiichi Sankyo (TSE:4568)/Eli Lilly (LLY) – Prasugrel for acute coronary syndromes (ACS)
Original PDUFA date: June 26, 2008
Extension date: Sept 26, 2008 (The FDA later missed this extended date in dramatic fashion and the drug ended up in front of a panel in Feb 2009. This is quite an extraordinary story and I’d suggest a little further reading if you’re unfamiliar with it).
Reason: “…based on supplemental information provided during the review period.”
Result: Approval – July 10, 2009
Salix Pharmaceuticals (SLXP) – METOZOLV (metoclopramide) NDA for gastroesophageal reflux disease (GERD)
Original PDUFA date: Nov 30, 2008
Extension date: Feb 27, 2009
Reason: “…to provide time for a full review of the submission.” No official reason given but this appears to be a standard three month extension based on the submission of additional data.
Result: CRL – Feb 26, 2009
United Therapeutics (UTHR) – Tyvaso (inhaled treprostinil) NDA for pulmonary hypertension
Original PDUFA date: Apr 30, 2009
Extension date: July 30, 2009
Reason: “The three-month extension was triggered by United Therapeutics’ April 2009 submission to the FDA of the results of a human factors study, which was considered a major amendment to the NDA.”
Result: Approval - July 30, 2009
Covidien (COV), Nuvo Research (TSX: NRI) – Pennsaid Topical Solution for the treatment of osteoarthritis of the knee.
Original PDUFA date: Aug 5, 2009
Extension date: Nov 4, 2009
Reason: “During the review process, Nuvo provided the FDA with supplemental information, which the Agency determined to be a major amendment to the Pennsaid New Drug Application.”
Result: Approval – Nov 5, 2009
Xenoport (XNPT)/GlaxoSmithKline (GSK) – Horizant (gabapentin enacarbil) NDA for restless leg syndrome
Original PDUFA date: Nov 9, 2009
Extension date: Feb 9, 2010
Reason: “The FDA determined that a Risk Evaluation and Mitigation Strategy (REMS) was necessary for GSK1838262. In response to FDA’s request, GSK submitted a proposed REMS. The FDA accepted this submission as a solicited major amendment to the GSK1838262 NDA.”
Result: CRL – Feb 17, 2010
Note: The delay between the extension date and final decision was weather related.
Cadence Pharma (CADX) - IV Acetaminophen NDA for pain
Original PDUFA date: Nov 12, 2009
Extension date: Feb 12, 2010
Reason: “The FDA designated one of Cadence’s submissions to the NDA, which contained additional clinical pharmacology data requested by the agency during the review process, as a major amendment.”
Result: CRL – Feb 11, 2010
Sepracor, now known as Sunovion - Stedesa NDA for seizure
Original PDUFA date: Jan 30, 2010
Extension date: April 30, 2010
Reason: “In November 2009, at the request of the FDA, Sepracor submitted additional information about STEDESA to the agency.”
Result: CRL – May 3, 2010
MannKind (MNKD) – Afrezza NDA for diabetes
Original PDUFA date: Jan 16, 2010
Extension date: Not given
Reason: “The FDA explained that it has not yet completed its inspection of the insulin manufacturing facilities of N.V. Organon, a third-party supplier to MannKind.”
Result: CRL – Mar 15, 2010
Note: While the extension appears to be almost three months to the day. This does not appear to be a standard additional data extension due to the reason given by MannKind (basically, I’m assuming they aren’t lying).
OSI Pharma (OSIP)/Genentech – Tarceva (erlotinib) sNDA for advanced non-small cell lung cancer
Original PDUFA date: Jan 18, 2010
Extension date: Apr 18, 2010
Reason: “The extension follows OSI’s submission of further data in support of the application.”
Result: Approved – Apr 16, 2010
Questcor (QCOR) – Acthar gel sNDA for Infantile Spasms
Original PDUFA date: June 11, 2010
Extension date: Sept 11, 2010
Reason: “The FDA extended the PDUFA date in order to review information regarding labeling and potential post-approval commitments that they solicited from Questcor.” Additional data triggered a three month extension.
Result: Approval - Oct 15, 2010
Warner Chilcott (WCRX) - Actonel (risedronate sodium) extended-release for osteoporosis
Original PDUFA date: July 24, 2010
Extension date: Oct 24, 2010
Reason: “…to allow sufficient time to review additional information solicited by the FDA and previously provided by the Company.”
Result: Approval – Oct 11, 2010
Cumberland Pharma (CPIX) – Acetadote sNDA for non-acetaminophen acute liver failure
Original PDUFA date: Sept 10, 2010
Extension date: Dec 10, 2010
Reason: No reason given. Appears to be based on the submission of additional data.
Result: CRL – Dec 22, 2010
AstraZeneca (AZN) – Ticagrelor (BRILINTA) NDA for Acute Coronary Syndromes (ACS).
Original PDUFA date: Sept 16, 2010
Extension date: Dec 16, 2010
Reason: No reason given. Appears to be based on the submission of additional data.
Result: CRL – Dec 17, 2010
Before analyzing the data, an important dichotomy must first be made: many delays were three month extensions, often triggered by submission of additional data, and the others appear to be due to the FDA simply needing more time. There should be much different results from either category based on this important difference. Keep in mind that MannKind’s current delay was not triggered by additional data and the delay for Benlysta was triggered by additional data (I’m assuming here, HGSI gave no reason for extension but reasons for a three month extension are almost always additional data).
First, let’s look at the ‘standard’ delays – the delays most pertinent to HGSI. In this case, there were thirteen total extensions that appear to be due to the submission of additional data. Of these extensions, seven resulted in approval and six resulted in a complete response letter (CRL). The approval rate for those NDA decisions, then, was 54%. This falls approximately in line with a 66% first cycle approval rate given by the FDA for 2006.
Perhaps more interesting, though, was the fact EVERY company that got a standard three month extension without providing a reason for said extension got a CRL. Three of three in this case. It may just be a correlation between ‘Good managements tend to keep their shareholders informed’ and ‘Good management tends to have a better approval percentage’, but I can’t help but wonder if these companies that withheld reasons that could have adversely affected their share prices. Whatever the case, it’ll be interesting to see if that holds up on decisions in the future.
HGSI, it should be noted, provided a reason for their three month extension.
For MannKind, on the other hand, we have significantly less data. In total, there is only record of three delays that were not standard three month extensions, four if you count Prasugrel’s lengthy unannounced second delay. In these cases, three of the four extensions resulted in approval – a 75% approval rate. The lone CRL, in fact, came from MannKind itself. And if MannKind’s extension was considered a standard additional data submission, contrary to my assumptions, then the approval rate climbs to 100%.
Due to the low number of delays similar to those of MannKind’s current delay, it’s hard to pull anything concrete from the data provided. In a more qualitative sense, however, it would appear that of all the delays given, the delays of Adolor’s Entereg and Spectrum’s Levoleucovorin are most similar to MannKind’s current delay. If you want to go that route, the delay is most certainly a good one; both of these delays resulted in approval.
It’s up to you how to interpret the above data, but I hope it provided a better insight into what delays might mean for approval of both Afrezza and Benlysta. My own conclusions, based as much on logical reasoning as it is on the data, are:
Three month delays due to submission of additional data mean virtually nothing in terms of change in approval odds.
Companies that receive three month extensions without providing a reason may be worthy of additional scrutiny.
Shorter delays by the FDA that are not based on additional data submission appear to be a good thing.
The market, then, may have been responding properly when MannKind’s share price popped by over 8% on the delay news. The delay of HGSI’s Benlysta, on the other hand, is unlikely to mean much of anything in terms of eventual approval odds.
Good luck to all of those carrying a position through MannKind’s FDA decision on ‘approximately’ January 24.
Disclosure: No positions.
What Does a Delay Mean for Eventual Approval? An Analysis
By Rockford Coscia, on January 5th, 2011
Recently, MannKind’s (MNKD) Afrezza NDA decision was delayed for ‘approximately four weeks’ with no reason given. The market responded positively, sending MNKD share prices up over 8% on the news, before eventually settling back into its pre-announcement trading range. But what does the delay actually mean for MannKind? And what about the delay for Human Genome Sciences’ Benlysta? Is there actually a trend between delays and the eventual outcome of the decision?
Some articles have hastily cobbled together some statistics about delays but unfortunately have fallen short of offering a real analysis. I therefore wanted to take a in-depth look at several NDA action date (aka PDUFA date) delays to dig up some data that might be actionable.
First let’s collect the data. Here is a run-down of several NDA action date delays, along with the reasons for the delay and the ultimate decision by the FDA. I’ve tried to be as comprehensive as possible, but if I’ve missed something please mention it in the comments and we’ll update our data. While the analysis is post-hoc and hardly statistically significant, it should be enough for us to establish some trends pertaining to the aforementioned delays.
Spectrum Pharmaceuticals (SPPI) - Levoleucovorin (calcium leucovorin, pure isomer) NDA for adjuvant for methotrexate
Original PDUFA date: Jan 11, 2008
Extension date: Mar 7, 2008
Reason: No reason given
Result: Approval – Mar 7, 2008
Adolor (ADLR)/GlaxoSmithKline (GSK) – ENTEREG (alvimopan) for the management of postoperative ileus (POI)
Original PDUFA date: Feb 10, 2008
1st Extension date: May 10, 2008
Reason: A REMS program was submitted and led to a three month extension (although not explicitly stated as the reason).
2nd Extension date: The FDA did not provide a specific date, but informed the company that it expects to issue the action letter shortly after the scheduled PDUFA date
Result: Approval – May 20, 2008
Daiichi Sankyo (TSE:4568)/Eli Lilly (LLY) – Prasugrel for acute coronary syndromes (ACS)
Original PDUFA date: June 26, 2008
Extension date: Sept 26, 2008 (The FDA later missed this extended date in dramatic fashion and the drug ended up in front of a panel in Feb 2009. This is quite an extraordinary story and I’d suggest a little further reading if you’re unfamiliar with it).
Reason: “…based on supplemental information provided during the review period.”
Result: Approval – July 10, 2009
Salix Pharmaceuticals (SLXP) – METOZOLV (metoclopramide) NDA for gastroesophageal reflux disease (GERD)
Original PDUFA date: Nov 30, 2008
Extension date: Feb 27, 2009
Reason: “…to provide time for a full review of the submission.” No official reason given but this appears to be a standard three month extension based on the submission of additional data.
Result: CRL – Feb 26, 2009
United Therapeutics (UTHR) – Tyvaso (inhaled treprostinil) NDA for pulmonary hypertension
Original PDUFA date: Apr 30, 2009
Extension date: July 30, 2009
Reason: “The three-month extension was triggered by United Therapeutics’ April 2009 submission to the FDA of the results of a human factors study, which was considered a major amendment to the NDA.”
Result: Approval - July 30, 2009
Covidien (COV), Nuvo Research (TSX: NRI) – Pennsaid Topical Solution for the treatment of osteoarthritis of the knee.
Original PDUFA date: Aug 5, 2009
Extension date: Nov 4, 2009
Reason: “During the review process, Nuvo provided the FDA with supplemental information, which the Agency determined to be a major amendment to the Pennsaid New Drug Application.”
Result: Approval – Nov 5, 2009
Xenoport (XNPT)/GlaxoSmithKline (GSK) – Horizant (gabapentin enacarbil) NDA for restless leg syndrome
Original PDUFA date: Nov 9, 2009
Extension date: Feb 9, 2010
Reason: “The FDA determined that a Risk Evaluation and Mitigation Strategy (REMS) was necessary for GSK1838262. In response to FDA’s request, GSK submitted a proposed REMS. The FDA accepted this submission as a solicited major amendment to the GSK1838262 NDA.”
Result: CRL – Feb 17, 2010
Note: The delay between the extension date and final decision was weather related.
Cadence Pharma (CADX) - IV Acetaminophen NDA for pain
Original PDUFA date: Nov 12, 2009
Extension date: Feb 12, 2010
Reason: “The FDA designated one of Cadence’s submissions to the NDA, which contained additional clinical pharmacology data requested by the agency during the review process, as a major amendment.”
Result: CRL – Feb 11, 2010
Sepracor, now known as Sunovion - Stedesa NDA for seizure
Original PDUFA date: Jan 30, 2010
Extension date: April 30, 2010
Reason: “In November 2009, at the request of the FDA, Sepracor submitted additional information about STEDESA to the agency.”
Result: CRL – May 3, 2010
MannKind (MNKD) – Afrezza NDA for diabetes
Original PDUFA date: Jan 16, 2010
Extension date: Not given
Reason: “The FDA explained that it has not yet completed its inspection of the insulin manufacturing facilities of N.V. Organon, a third-party supplier to MannKind.”
Result: CRL – Mar 15, 2010
Note: While the extension appears to be almost three months to the day. This does not appear to be a standard additional data extension due to the reason given by MannKind (basically, I’m assuming they aren’t lying).
OSI Pharma (OSIP)/Genentech – Tarceva (erlotinib) sNDA for advanced non-small cell lung cancer
Original PDUFA date: Jan 18, 2010
Extension date: Apr 18, 2010
Reason: “The extension follows OSI’s submission of further data in support of the application.”
Result: Approved – Apr 16, 2010
Questcor (QCOR) – Acthar gel sNDA for Infantile Spasms
Original PDUFA date: June 11, 2010
Extension date: Sept 11, 2010
Reason: “The FDA extended the PDUFA date in order to review information regarding labeling and potential post-approval commitments that they solicited from Questcor.” Additional data triggered a three month extension.
Result: Approval - Oct 15, 2010
Warner Chilcott (WCRX) - Actonel (risedronate sodium) extended-release for osteoporosis
Original PDUFA date: July 24, 2010
Extension date: Oct 24, 2010
Reason: “…to allow sufficient time to review additional information solicited by the FDA and previously provided by the Company.”
Result: Approval – Oct 11, 2010
Cumberland Pharma (CPIX) – Acetadote sNDA for non-acetaminophen acute liver failure
Original PDUFA date: Sept 10, 2010
Extension date: Dec 10, 2010
Reason: No reason given. Appears to be based on the submission of additional data.
Result: CRL – Dec 22, 2010
AstraZeneca (AZN) – Ticagrelor (BRILINTA) NDA for Acute Coronary Syndromes (ACS).
Original PDUFA date: Sept 16, 2010
Extension date: Dec 16, 2010
Reason: No reason given. Appears to be based on the submission of additional data.
Result: CRL – Dec 17, 2010
Before analyzing the data, an important dichotomy must first be made: many delays were three month extensions, often triggered by submission of additional data, and the others appear to be due to the FDA simply needing more time. There should be much different results from either category based on this important difference. Keep in mind that MannKind’s current delay was not triggered by additional data and the delay for Benlysta was triggered by additional data (I’m assuming here, HGSI gave no reason for extension but reasons for a three month extension are almost always additional data).
First, let’s look at the ‘standard’ delays – the delays most pertinent to HGSI. In this case, there were thirteen total extensions that appear to be due to the submission of additional data. Of these extensions, seven resulted in approval and six resulted in a complete response letter (CRL). The approval rate for those NDA decisions, then, was 54%. This falls approximately in line with a 66% first cycle approval rate given by the FDA for 2006.
Perhaps more interesting, though, was the fact EVERY company that got a standard three month extension without providing a reason for said extension got a CRL. Three of three in this case. It may just be a correlation between ‘Good managements tend to keep their shareholders informed’ and ‘Good management tends to have a better approval percentage’, but I can’t help but wonder if these companies that withheld reasons that could have adversely affected their share prices. Whatever the case, it’ll be interesting to see if that holds up on decisions in the future.
HGSI, it should be noted, provided a reason for their three month extension.
For MannKind, on the other hand, we have significantly less data. In total, there is only record of three delays that were not standard three month extensions, four if you count Prasugrel’s lengthy unannounced second delay. In these cases, three of the four extensions resulted in approval – a 75% approval rate. The lone CRL, in fact, came from MannKind itself. And if MannKind’s extension was considered a standard additional data submission, contrary to my assumptions, then the approval rate climbs to 100%.
Due to the low number of delays similar to those of MannKind’s current delay, it’s hard to pull anything concrete from the data provided. In a more qualitative sense, however, it would appear that of all the delays given, the delays of Adolor’s Entereg and Spectrum’s Levoleucovorin are most similar to MannKind’s current delay. If you want to go that route, the delay is most certainly a good one; both of these delays resulted in approval.
It’s up to you how to interpret the above data, but I hope it provided a better insight into what delays might mean for approval of both Afrezza and Benlysta. My own conclusions, based as much on logical reasoning as it is on the data, are:
Three month delays due to submission of additional data mean virtually nothing in terms of change in approval odds.
Companies that receive three month extensions without providing a reason may be worthy of additional scrutiny.
Shorter delays by the FDA that are not based on additional data submission appear to be a good thing.
The market, then, may have been responding properly when MannKind’s share price popped by over 8% on the delay news. The delay of HGSI’s Benlysta, on the other hand, is unlikely to mean much of anything in terms of eventual approval odds.
Good luck to all of those carrying a position through MannKind’s FDA decision on ‘approximately’ January 24.
Disclosure: No positions.
Mannkind ...Afrezza approval is a good bet 13 comments
Jan 7, 2011 5:19 PM | about stocks: MNKD
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Share0 Mannkind is a pharmaceutical company with one product close to approval, Afrezza, an inhaled insulin. In my opinion, Afrezza will be approved around January 21, 2011. The FDA is concerned with safety, efficacy, and clinical need.
1) Let's examine efficacy first. In several major trials spanning thousands of patients and almost a decade, Afrezza has shown that HBA1C, i.e. blood glucose level over an average period of time, was as good as rapid acting injected insulin, i.e. lispro. Primary end points of all of these trials were met. Importantly, all of the secondary end points were also met. Afrezza usage was characterized by substantially fewer hypoglycemic events, lower post prandial glucose (PPG), lower fasting blood glucose (FBG), and less weight gain and even weight loss. A recent study also shows that Afrezza works in a different way than lispro such that Afrezza is safer because efficacy is maintained without hypoglycemia regardless of carbohydrate intake at meal time. This will require more study; but it is important.
2) Now let's examine safety. Does Afrezza result in significantly lower lung function over time? Four years of trial data show that the old inhaler resulted in lower lung function than the control group, but that this lower lung function was not statistically significant. Recent data submitted to the FDA shows that the new inhaler actually results in no lung function difference; however, the trial was very short term. More studies will be need to show this. Either way, the trial end points were met. The second question is does Afrezza cause tumors and is there residual insulin buildup in the lungs? Two studies (106 and 52 week rat and mouse studies) and patient CT scans revealed no tumor or carcinogenic effect or surfactant action or insulin buildup. Finally, does Afrezza adversely impact cardio function? QT trial data showed that Afrezza causes no QT delay.
3) Patient need? One of the biggest issues with injected insulin is patient compliance. There are several issues. Many patients have difficulty with the rigors of carb counting, injection and glucose monitoring. The bottom line is that patients who take Afrezza will tend to remain more compliant because all of these are less difficult while using Afrezza. That's a big big, really really good thing in the diabetes world. Furthermore, because injected insulin peaks too late after meal time and remains in the system at higher levels than needed long after the meal is digested, patients are prone to hypoglycemia. Afrezza solves this problem by peaking early during the meal and moving out of the system after three hours.
4) In March 2010, Mannkind received a CRL in which the FDA asked for clarification as to how Afrezza fits into the armamentarium of diabetes treatment. The FDA asked that the bioequivalency trial data comparing inhalers be resubmitted ina new format. The FDA also asked for certain packaging label clarification. The FDA did not ask for new efficacy or safety data. Indeed, this was a CRL "light" so to speak. Mannkind met with the FDA June 2010 and submitted a class 2 resubmission which the FDA typically handles in about 6 months. Now the FDA in December stated that it would need about four more weeks in order to make a decision, but did not ask for more data. January 21, 2011 is about 6 months after the FDA originally accepted the resubmission. That is a good sign.
It's not easy to predict FDA approvals, but it could be worth it here because many people are still skeptical, meaning that if Afrezza is approved the stock could increase in price substantially. Increasing that return could be a partnership which Al Mann (Mannkind's billionaire CEO, COB and 43% owner) has stated will probably happen after approval. This could be a very good time to own Mannkind shares.
JR
Themes: biotech, diabetes, insulin, inhaler, pharmaceutical, drug Stocks: MNKD
Jan 7, 2011 5:19 PM | about stocks: MNKD
Font: PrintEmail Recommend 2 Share this page
Share0 Mannkind is a pharmaceutical company with one product close to approval, Afrezza, an inhaled insulin. In my opinion, Afrezza will be approved around January 21, 2011. The FDA is concerned with safety, efficacy, and clinical need.
1) Let's examine efficacy first. In several major trials spanning thousands of patients and almost a decade, Afrezza has shown that HBA1C, i.e. blood glucose level over an average period of time, was as good as rapid acting injected insulin, i.e. lispro. Primary end points of all of these trials were met. Importantly, all of the secondary end points were also met. Afrezza usage was characterized by substantially fewer hypoglycemic events, lower post prandial glucose (PPG), lower fasting blood glucose (FBG), and less weight gain and even weight loss. A recent study also shows that Afrezza works in a different way than lispro such that Afrezza is safer because efficacy is maintained without hypoglycemia regardless of carbohydrate intake at meal time. This will require more study; but it is important.
2) Now let's examine safety. Does Afrezza result in significantly lower lung function over time? Four years of trial data show that the old inhaler resulted in lower lung function than the control group, but that this lower lung function was not statistically significant. Recent data submitted to the FDA shows that the new inhaler actually results in no lung function difference; however, the trial was very short term. More studies will be need to show this. Either way, the trial end points were met. The second question is does Afrezza cause tumors and is there residual insulin buildup in the lungs? Two studies (106 and 52 week rat and mouse studies) and patient CT scans revealed no tumor or carcinogenic effect or surfactant action or insulin buildup. Finally, does Afrezza adversely impact cardio function? QT trial data showed that Afrezza causes no QT delay.
3) Patient need? One of the biggest issues with injected insulin is patient compliance. There are several issues. Many patients have difficulty with the rigors of carb counting, injection and glucose monitoring. The bottom line is that patients who take Afrezza will tend to remain more compliant because all of these are less difficult while using Afrezza. That's a big big, really really good thing in the diabetes world. Furthermore, because injected insulin peaks too late after meal time and remains in the system at higher levels than needed long after the meal is digested, patients are prone to hypoglycemia. Afrezza solves this problem by peaking early during the meal and moving out of the system after three hours.
4) In March 2010, Mannkind received a CRL in which the FDA asked for clarification as to how Afrezza fits into the armamentarium of diabetes treatment. The FDA asked that the bioequivalency trial data comparing inhalers be resubmitted ina new format. The FDA also asked for certain packaging label clarification. The FDA did not ask for new efficacy or safety data. Indeed, this was a CRL "light" so to speak. Mannkind met with the FDA June 2010 and submitted a class 2 resubmission which the FDA typically handles in about 6 months. Now the FDA in December stated that it would need about four more weeks in order to make a decision, but did not ask for more data. January 21, 2011 is about 6 months after the FDA originally accepted the resubmission. That is a good sign.
It's not easy to predict FDA approvals, but it could be worth it here because many people are still skeptical, meaning that if Afrezza is approved the stock could increase in price substantially. Increasing that return could be a partnership which Al Mann (Mannkind's billionaire CEO, COB and 43% owner) has stated will probably happen after approval. This could be a very good time to own Mannkind shares.
JR
Themes: biotech, diabetes, insulin, inhaler, pharmaceutical, drug Stocks: MNKD
Jan. 12, 2011, 11:28 p.m. EST
MannKind CEO bets big on diabetes drug
Mann has contributed over half of $1.5 billion used on AfrezzaExplore related topics
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|Recommend PrintEmail AlertBy John Letzing, MarketWatch
SAN FRANCISCO (MarketWatch) — MannKind Corp. Chief Executive Alfred Mann has poured a considerable amount of his personal fortune into developing the company’s inhaled insulin treatment for diabetes, contributing well over half of the $1.5 billion invested in the drug so far.
The insulin treatment, Afrezza, is expected to receive a decision on approval from the U.S. Food and Drug Administration later this month.
New chapter for insulinDr. Alfred Mann, CEO of Mannkind Corp., has developed an inhaled form of insulin, which the FDA is expected to decide on later this month. The product, called Afrezza, would be a major breakthrough in diabetes care, as it would greatly reduce the need for needles.
The FDA informed MannKind /quotes/comstock/15*!mnkd/quotes/nls/mnkd (MNKD 9.01, -0.03, -0.33%) late last month that it needed to delay for roughly four weeks its decision on the highly-anticipated treatment, which could provide an inhaled alternative to insulin injections for diabetes patients.
Mann said he’s cautiously optimistic that Afrezza will be approved.
“I have personally invested $925 million of the $1.5 billion that’s been invested in this product,” Mann said during an interview on Wednesday.
Afrezza could be a blockbuster for MannKind, said Mann, who noted that the company has no other commercialized products.
MannKind has in “the order of ten” other products in development, the CEO said, though “they’re years away.”
While other companies have made ill-fated forays into inhaled insulin in the past, including Pfizer Inc. /quotes/comstock/13*!pfe/quotes/nls/pfe (PFE 18.36, -0.01, -0.05%) , Mann said his firm’s treatment is distinguished by its ease of use and effectiveness.
“The only thing Pfizer had was an inhalation which frankly was in a large, inconvenient mechanism that had to be done multiple times, was expensive, and didn’t produce results as good as what you get with injections,” Mann said.
Mann said that delays from the FDA on drug approvals are not uncommon.
During a presentation at the JP Morgan Healthcare Conference in San Francisco later on Wednesday, Mann told an audience that while MannKind has not received specific reasons from the FDA for its delay in deciding on Afrezza, he assumes that it’s attributable to a slowdown during the recent holiday season.
“My guess is they just didn’t have it all done, given the holidays,” Mann said. “They’re being very, very thorough, as they should be.”
Mann previously founded MiniMed Inc., a diabetes therapy developer sold for $3.7 billion to Medtronic Inc. /quotes/comstock/13*!mdt/quotes/nls/mdt (MDT 36.70, +0.18, +0.49%) in 2001.
Last year, Forbes listed Mann as one of the world’s wealthiest individuals, with an estimated net worth of $1.4 billion.
John Letzing is a MarketWatch reporter based in San Francisco.
MannKind CEO bets big on diabetes drug
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|Recommend PrintEmail AlertBy John Letzing, MarketWatch
SAN FRANCISCO (MarketWatch) — MannKind Corp. Chief Executive Alfred Mann has poured a considerable amount of his personal fortune into developing the company’s inhaled insulin treatment for diabetes, contributing well over half of the $1.5 billion invested in the drug so far.
The insulin treatment, Afrezza, is expected to receive a decision on approval from the U.S. Food and Drug Administration later this month.
New chapter for insulinDr. Alfred Mann, CEO of Mannkind Corp., has developed an inhaled form of insulin, which the FDA is expected to decide on later this month. The product, called Afrezza, would be a major breakthrough in diabetes care, as it would greatly reduce the need for needles.
The FDA informed MannKind /quotes/comstock/15*!mnkd/quotes/nls/mnkd (MNKD 9.01, -0.03, -0.33%) late last month that it needed to delay for roughly four weeks its decision on the highly-anticipated treatment, which could provide an inhaled alternative to insulin injections for diabetes patients.
Mann said he’s cautiously optimistic that Afrezza will be approved.
“I have personally invested $925 million of the $1.5 billion that’s been invested in this product,” Mann said during an interview on Wednesday.
Afrezza could be a blockbuster for MannKind, said Mann, who noted that the company has no other commercialized products.
MannKind has in “the order of ten” other products in development, the CEO said, though “they’re years away.”
While other companies have made ill-fated forays into inhaled insulin in the past, including Pfizer Inc. /quotes/comstock/13*!pfe/quotes/nls/pfe (PFE 18.36, -0.01, -0.05%) , Mann said his firm’s treatment is distinguished by its ease of use and effectiveness.
“The only thing Pfizer had was an inhalation which frankly was in a large, inconvenient mechanism that had to be done multiple times, was expensive, and didn’t produce results as good as what you get with injections,” Mann said.
Mann said that delays from the FDA on drug approvals are not uncommon.
During a presentation at the JP Morgan Healthcare Conference in San Francisco later on Wednesday, Mann told an audience that while MannKind has not received specific reasons from the FDA for its delay in deciding on Afrezza, he assumes that it’s attributable to a slowdown during the recent holiday season.
“My guess is they just didn’t have it all done, given the holidays,” Mann said. “They’re being very, very thorough, as they should be.”
Mann previously founded MiniMed Inc., a diabetes therapy developer sold for $3.7 billion to Medtronic Inc. /quotes/comstock/13*!mdt/quotes/nls/mdt (MDT 36.70, +0.18, +0.49%) in 2001.
Last year, Forbes listed Mann as one of the world’s wealthiest individuals, with an estimated net worth of $1.4 billion.
John Letzing is a MarketWatch reporter based in San Francisco.
der Bear Raid gerade eben war nicht von schlechten Eltern, von $9,8 auf $6 innerhalb weniger Minuten, und das bei einer Firma mit knapp einer Milliarde Marktkapitalisierung.
inzwischen ist der Kurs aber wieder bei 9, habe es erst im nachhinein mitbekommen.
Dabei wurden sicher alle Stoploss-Setzungen wegrasiert. Dabei weiss man doch von Dendreon und Avanir dass man vor Zulassungsentscheidungen kein SL setzen darf:
inzwischen ist der Kurs aber wieder bei 9, habe es erst im nachhinein mitbekommen.
Dabei wurden sicher alle Stoploss-Setzungen wegrasiert. Dabei weiss man doch von Dendreon und Avanir dass man vor Zulassungsentscheidungen kein SL setzen darf:
Halted, Daumen drücken!
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