DURECT Corporation Announces Topline Results from Phase 2b AHFIRM Trial of Larsucosterol in Alcohol-Associated Hepatitis with Promising Effect on Mortality

• Both the 30 mg and 90 mg larsucosterol doses demonstrated a compelling and clinically meaningful trend in reduction of mortality at 90 days, the key secondary endpoint, with mortality reductions of 41% (p=0.070) in the 30 mg arm and 35% (p=0.126) in the 90 mg arm compared with SOC.
• The numerical improvement in the primary endpoint of mortality or transplant at 90 days did not achieve statistical significance for either dose of larsucosterol.
• Both doses of larsucosterol showed a more pronounced reduction in mortality in patients enrolled in the U.S., representing 76% of patients enrolled in the trial. The reductions in mortality at 90 days were 57% (p=0.014) for the 30 mg arm and 58% (p=0.008) for the 90 mg arm compared with SOC.
• Larsucosterol was safe and well tolerated. There were fewer treatment-emergent adverse events (TEAEs) in the larsucosterol arms compared with SOC.

DURECT intends to have an End of Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) to discuss the trial results and the Phase 3 registration trial design in the first quarter of 2024.  DURECT also intends to present the results of AHFIRM at an upcoming medical meeting.

"The topline results from AHFIRM provide compelling evidence that administration of larsucosterol can reduce mortality at 90 days in this devastating disease," said James E. Brown, D.V.M., President and CEO of DURECT.  "We have strong rationale to advance larsucosterol into a Phase 3 registration trial designed with adequate power to detect a statistically significant result using 90-day mortality as the primary endpoint. We look forward to meeting with the FDA to discuss next steps.  Based on the strength of the clinical data generated to date, if approved, larsucosterol could save many patient lives.  We extend our thanks to all the patients, families, clinical trial investigators, and staff across the multiple sites globally who have worked with the DURECT team to bring larsucosterol to this advanced stage."

Craig McClain, M.D., AGAF, FACG, FAASLD, FACN, Professor of Medicine and Pharmacology & Toxicology at University of Louisville School of Medicine, commented, "In my practice, I treat AH patients frequently and can personally attest to the frustration of the hepatology community at the lack of effective treatment options for these critically ill patients. The AHFIRM trial results represent the most promising data set I have seen on new therapy for severe AH with no important toxicity and a trend toward reducing mortality."

Norman Sussman, M.D., FAASLD, Chief Medical Officer at DURECT, added, "Patients with alcohol-associated hepatitis are extremely ill and have a high mortality in the three months following hospital admission. The AHFIRM trial provides strong evidence that larsucosterol has the potential to reduce 90-day mortality and has demonstrated an excellent safety profile to date.  We are continuing to analyze the AHFIRM data to fully understand the results and to inform future trials and our discussion with the FDA."

Key AHFIRM trial results:

Mortality or Liver Transplantation at 90 Days

The primary endpoint for the AHFIRM trial was the reduction in mortality or liver transplantation at 90 days.  The endpoint was analyzed using a hierarchical assessment of patient outcomes to calculate a win probability for each of the 30 mg and 90 mg dose of larsucosterol compared with SOC. The results for the primary endpoint were not statistically significant for either the 30 mg or 90 mg doses compared with SOC, though a numerical improvement was observed.

Mortality at 90 Days

Mortality at 90 Days was a key secondary endpoint for the AHFIRM trial.  In this analysis, the 30 mg and 90 mg doses of larsucosterol showed numerical trends toward a clinically meaningful survival benefit with 90-day mortality reductions of 41% and 35%, respectively, when compared to SOC, although these results were not statistically significant. 

Mortality at 90 Days (U.S. patients) 

When further analyzed by geography, both the 30 mg and 90 mg doses showed an enhanced survival benefit at 90 days with reductions in 90-day mortality of 57% and 58%, respectively, in patients enrolled in the U.S., which represented 76% of the total patients enrolled. 

Group	Mortality at 90 Days	% Reduction vs. SOC	Difference vs. SOC	p-value
Larsucosterol 30 mg (n=76)	12.3 %	-56.8 %	-16.1 %	0.014
SOC (n=78)	28.5 %
Larsucosterol 90 mg (n=78)	11.7 %	-58.1 % Werbung Mehr Nachrichten zur Durect Aktie kostenlos abonnieren E-Mail-Adresse Bitte überprüfe deine die E-Mail-Adresse. Benachrichtigungen von ARIVA.DE (Mit der Bestellung akzeptierst du die Datenschutzhinweise) -1 Vielen Dank, dass du dich für unseren Newsletter angemeldet hast. Du erhältst in Kürze eine E-Mail mit einem Aktivierungslink. Hinweis: ARIVA.DE veröffentlicht in dieser Rubrik Analysen, Kolumnen und Nachrichten aus verschiedenen Quellen. Die ARIVA.DE AG ist nicht verantwortlich für Inhalte, die erkennbar von Dritten in den „News“-Bereich dieser Webseite eingestellt worden sind, und macht sich diese nicht zu Eigen. Diese Inhalte sind insbesondere durch eine entsprechende „von“-Kennzeichnung unterhalb der Artikelüberschrift und/oder durch den Link „Um den vollständigen Artikel zu lesen, klicken Sie bitte hier.“ erkennbar; verantwortlich für diese Inhalte ist allein der genannte Dritte. Andere Nutzer interessierten sich auch für folgende News 18.05.24 - Small- & Micro Cap ... Technologieführerschaft als Wettbewerbsvorteil – Tesla, De.mem, Nvidia 18.05.24 - Boersia.de Johnson & Johnson Aktie: Insiderverkäufe und Firmenkauf 18.05.24 - wallstreetONLINE ... Outperformance: Mit 4 Aktienfonds wie Warren Buffett die Benchmark schlagen