– Altimmune, Inc. (NASDAQ:ALT), a clinical-stage biopharmaceutical company, today announced topline results from its 24-week (12-week extension) trial of pemvidutide in subjects with NAFLD.
Sixty-six (66) of the 83 subjects who completed the initial 12-week Phase 1b NAFLD trial consented to participate in this 12-week extension trial to receive a total of 24 weeks of treatment, and 64 subjects were enrolled. The trial was conducted without adjunctive diet and exercise interventions and the double-blinding of the trial was maintained during the extension study. The same endpoints as the 12-week parent NAFLD trial were employed, with a primary efficacy endpoint of percent (%) reduction in liver fat content; key secondary endpoints were reduction in liver inflammation, as measured by serum ALT levels and cT1, and percent weight loss.
The population of the 12-week extension trial had similar baseline characteristics as the population of the parent, 12-week Phase 1b NAFLD trial. At baseline, across all treatment groups, mean BMI was 36.7 kg/m2 and mean liver fat content (LFC), as measured by MRI-PDFF, was 22.2%. Type 2 diabetes was present in 26.6% of subjects and 73.4% of study subjects were of Hispanic ethnicity.
The trial met its primary endpoint in all pemvidutide treatment groups. At the 1.8 mg and 2.4 mg doses, subjects receiving pemvidutide achieved mean relative reductions of liver fat content of 75.2% and 76.4%, respectively; 92.3% and 100% of subjects, respectively, achieved a 30% reduction in liver fat, 84.6% and 72.7% of subjects, respectively, achieved a 50% reduction in liver fat, and 53.8% and 45.5% of subjects, respectively, achieved normalization of liver fat, defined as liver fat fraction of 5% or less. Statistically significant declines in mean serum ALT levels were observed in all pemvidutide-treated subjects, and in subjects with baseline serum ALT ≥30 IU/L, ALT levels declined at least 17 IU/L at all pemvidutide dose levels. In a subset of subjects evaluated for cT1 response, 75.0% and 100% of subjects receiving 1.8 mg or 2.4 mg pemvidutide, respectively, achieved an 80 millisecond (ms) decrease in cT1. Elevated cT1 levels have been associated with increased risk of major adverse cardiac events (MACE) and major adverse liver outcomes (MALO), and an 80 ms reduction has been associated with a 2-point reduction of NAFLD Activity Score (NAS).
The trial also met its key secondary weight loss endpoint in all pemvidutide treatment groups. Employing an efficacy estimand, mean weight losses of 7.2% (placebo-adjusted 6.0%) in subjects without diabetes and 6.2% (placebo-adjusted 4.8%) in all subjects were achieved at the 1.8 mg dose.
Pemvidutide was generally well tolerated. A total of 3 serious or severe adverse events (AEs) were reported, each unrelated to study drug administration (chest pain post-elective cardiac stent placement; Salmonella infection; and hypertension greater than 3 weeks after the completion of treatment). Three AEs led to treatment discontinuation, 1 being the Salmonella infection, and 2 gastrointestinal AEs, 1 (6.3%) at the 1.2 mg dose and 1 (6.7%) at the 1.8 mg dose. As expected, gastrointestinal events comprised the majority of AEs and were predominantly mild in nature. No clinically significant ALT elevations were observed. Glycemic control was maintained, with pemvidutide groups demonstrating trends toward improvements in fasting glucose and HbA1c over the 24 weeks of treatment. Meaningful reductions in systolic blood pressure were observed, and increases in heart rate, typical of the incretin class of agents, were minimal at 0 to 4 beats per minute and independent of dose.
“We have seen in recent study announcements that the magnitudes of change in non-invasive markers like liver fat reduction and ALT are associated with improvement in non-alcoholic steatohepatitis (NASH) histopathology. The impressive results announced today suggest a high likelihood of success on histopathological assessment in Phase 2b,” said Stephen Harrison, M.D., Chairman and Co-Founder of Pinnacle Clinical Research and Summit Clinical Research. “Effective weight loss is also extremely important for these patients, as many suffer from metabolic co-morbidities such as obesity, hyperlipidemia and diabetes putting them at greater risk for cardiovascular disease. I believe pemvidutide is one of the few candidate drugs for NASH with the potential to deliver in a meaningful way on both NASH activity and weight loss and that the magnitude and consistency of these results place pemvidutide among the most promising agents in development for NASH.”
“These results, which include some of the most compelling reductions in liver fat content observed to date, together with robust reductions in ALT and cT1, highlight the potential for pemvidutide to achieve significant rates of NASH resolution and fibrosis improvement in biopsy-driven NASH trials,” said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. “We believe that both NASH and obesity are important value drivers of our pemvidutide program. We look forward to the weight loss data from the interim analysis of our MOMENTUM obesity trial in Q1 2023 and commencing a Phase 2b NASH trial in 2023.”
