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Altimmune Announces 2-Week Phase 1b Clinical Trial Of Pemvidutide In Subjects With NAFLD Achieved Primary Endpoint

All 3 pemvidutide dosing groups (1.2 mg, 1.8 mg, 2.4 mg) achieved the primary endpoint of relative and absolute reductions in liver fat, with a 68.5% relative reduction in liver fat content in subjects

Benzinga · 09/14/2022 07:01
  • All 3 pemvidutide dosing groups (1.2 mg, 1.8 mg, 2.4 mg) achieved the primary endpoint of relative and absolute reductions in liver fat, with a 68.5% relative reduction in liver fat content in subjects receiving 1.8 mg dose at 12 weeks of treatment
     
  • Mean weight loss of 4.9% (placebo-adjusted 4.7%) in subjects without diabetes receiving 1.8 mg dose at 12 weeks of treatment
  • Altimmune to host conference call today at 8:30 am ET

GAITHERSBURG, Md., Sept. 14, 2022 (GLOBE NEWSWIRE) -- Altimmune, Inc. (NASDAQ:ALT), a clinical-stage biopharmaceutical company, today announced positive topline results from its 12-week Phase 1b study of pemvidutide1 in subjects with non-alcoholic fatty liver disease (NAFLD).

The trial was a randomized, double-blind, placebo-controlled study, with Dr. Stephen A. Harrison, Medical Director, Pinnacle Research, serving as the Principal Investigator. Subjects were randomized 1:1:1:1 to 1.2 mg, 1.8 mg, 2.4 mg pemvidutide or placebo administered weekly for 12 weeks. No dose titration was used with 1.2 mg or 1.8 mg dose, while a short 4-week dose titration was employed at the 2.4 mg dose. The primary efficacy endpoint was the percent (%) reduction in liver fat content from baseline, and the key secondary efficacy endpoint was the % weight loss from baseline, both at 12 weeks of treatment. The trial was conducted without adjunctive diet and exercise interventions that are the standard for obesity trials.

Ninety-four (94) subjects were randomized and treated at 13 sites across the U.S. Mean BMI at baseline was approximately 36 kg/m2 and mean liver fat content (LFC), as measured by MRI-PDFF, was approximately 22%. Twenty-seven (29%) subjects had type 2 diabetes at baseline, and approximately 75% of study subjects were of Hispanic ethnicity.

The trial met its primary endpoint in all pemvidutide treatment groups. At the 1.8 mg dose (with and without diabetes), pemvidutide achieved a mean reduction of liver fat content of 68.5%, with 94.4% of subjects achieving a 30% reduction in liver fat, 72.2% achieving a 50% reduction in liver fat, and 55.6% of subjects achieving normalization of liver fat, defined as liver fat fraction of 5% or less. In addition, mean serum alanine aminotransferase (ALT) levels declined in all subjects, and in subjects with baseline serum ALT above 30 IU/L, levels declined more than 17 IU/L at all dose levels and 27.0 IU/L in the 2.4 mg dose cohort.

The trial also met its key secondary endpoint in all pemvidutide treatment groups. Employing an efficacy estimand, mean weight losses of 4.9% (placebo-adjusted 4.7%) in subjects without diabetes and 4.4% in subjects with diabetes (placebo-adjusted 3.9%) were achieved at the 1.8 and 2.4 mg doses, respectively.

Pemvidutide was reported to be generally well tolerated. Gastrointestinal events comprised the majority of the adverse events (AEs). Even without dose titration, the symptoms experienced by subjects were predominantly mild and transient in nature, consistent with known GLP-1 class effects. No serious or severe AEs were reported. Two subjects treated with pemvidutide discontinued treatment due to AEs [1 (4.3%) at 1.8 mg and 1 (4.2%) at 2.4 mg], both secondary to gastrointestinal intolerability. No clinically significant ALT elevations (defined as an increase to 3-fold or greater the upper limit of normal) were observed. Glycemic control was unaffected, with no clinically meaningful changes in HbA1c or fasting glucose. Clinically meaningful reductions in systolic blood pressure were observed, along with the 2-3 beat per minute increase in heart rate typical for GLP-1 class of drugs.

"We are pleased with the results of this trial, including the extent of liver fat and serum ALT reductions. Weight loss was within our target range, and good tolerability was observed without the need for dose titration. In addition, no clinically significant ALT elevations were observed," said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. "With these positive results in hand, we look forward to reporting data from the 24-week NAFLD trial, as well as 24-week interim data from our MOMENTUM obesity trial."

Dr. Stephen Harrison, Principal Investigator, remarked, "Significant reductions in the liver fat fraction and serum ALT have been shown to correlate with improvement of non-alcoholic steatohepatitis (NASH) in clinical trials. The marked decreases in both liver fat and serum ALT, together with approximately 5% weight loss in just 12 weeks in this NAFLD patient population, highlight pemvidutide as potentially a promising therapeutic for both NASH and obesity." Dr. Harrison also noted, "It is important to recognize that the baseline liver fat content and demographics in this study diverged substantially from a typical obesity study population."