DURECT Corporation announced topline results from its AHFIRM trial, a Phase 2b randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of larsucosterol in 307 patients with severe alcohol-associated hepatitis (AH). Topline data from AHFIRM showed: 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. 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. Safety and Tolerability: Both the 30 mg and 90 mg doses of larsucosterol were well tolerated. There were fewer TEAEs in the larsucosterol arms compared with SOC.