Altimmune (NASDAQ:ALT) reported positive top-line results from its Phase II RECLAIM trial evaluating pemvidutide in adults with moderate to severe alcohol use disorder, or AUD, with the company saying the study met its primary endpoint and several secondary measures after 24 weeks of treatment.
The randomized, placebo-controlled study enrolled 100 patients across 12 sites. Participants received either pemvidutide at a target dose of 2.4 milligrams once weekly or placebo. Patients in the treatment arm titrated monthly from 1.2 milligrams to 1.8 milligrams and then to 2.4 milligrams.
Heavy Drinking Days Primary Endpoint Met
The trial’s primary endpoint was the change from baseline in average heavy drinking days per week. At week 24, pemvidutide produced a placebo-adjusted reduction of 1.45 heavy drinking days per week, with a p-value of 0.0014, according to the company.
Christophe Arbet-Engels, Altimmune’s chief medical officer, said the effect was evident by week four and continued through the treatment period. Baseline heavy drinking days averaged 5.9 per week in the pemvidutide group and 5.6 per week in the placebo group.
The study also met secondary endpoints tied to measures recognized by the FDA for potential registration studies in AUD. A two-level reduction in World Health Organization Risk Drinking Levels was achieved by 64.4% of patients receiving pemvidutide, compared with 34.8% of placebo patients, with a p-value of 0.0049.
In addition, pemvidutide showed a statistically significant improvement in the percentage of patients achieving zero heavy drinking days, with a p-value of 0.0066. Arbet-Engels said more than twice as many pemvidutide-treated patients reached that outcome compared with placebo-treated patients, though the company did not provide the exact percentages during the call.
Objective Alcohol-Intake Measure and Weight Results
Altimmune also reported results for phosphatidylethanol, or PEth, a blood-based biomarker intended to reflect alcohol intake over the prior two to four weeks. Patients began the study with PEth levels of roughly 380 nanograms per milliliter. At week 24, pemvidutide demonstrated a placebo-adjusted reduction of 175.3 nanograms per milliliter, with a p-value of 0.0001, while the placebo group’s PEth levels were described as unchanged.
Management said the results across patient-reported drinking outcomes and the objective PEth measurement were consistent. In response to an analyst question, Arbet-Engels said patient-reported measures may show a placebo effect when patients alter their reporting or drinking patterns after enrolling in a study, while PEth provides an objective measure of recent intake.
Pemvidutide also produced a statistically significant 9.1% reduction in body weight from baseline versus placebo at week 24, Altimmune said.
The company reported exploratory liver-related findings among participants with a baseline FIB-4 index greater than 1.3, a threshold associated with an increased risk of liver fibrosis. Altimmune said 50% of pemvidutide-treated patients in that group achieved a FIB-4 score below 1.3 after 24 weeks, compared with 17% of placebo patients. The company said it intends to evaluate potential liver effects further in future studies.
Safety, Retention and Next Steps
Altimmune said pemvidutide was generally well tolerated, with most adverse events mild to moderate. Eighty percent of patients receiving pemvidutide completed treatment, compared with 78% in the placebo group, while 91% of all participants completed the study.
Six placebo patients discontinued treatment because of lack of efficacy, while no pemvidutide-treated patients discontinued for that reason, according to the company. Gastrointestinal adverse events accounted for most treatment-related discontinuations. Altimmune reported two serious adverse events: breast cancer and hyponatremia. The investigator considered the hyponatremia case possibly related to study medication, while Arbet-Engels said an independent external expert concluded it was not related to the study drug.
The company said nausea occurred in 44% of patients at the 2.4-milligram dose in RECLAIM, compared with 52% in a prior obesity study using the same dose. Management said the monthly titration approach may have contributed to the tolerability profile, while cautioning that comparisons across different trials and patient populations are limited.
Durso said a future Phase III AUD program is expected to be smaller and shorter than Altimmune’s planned Phase III program in metabolic dysfunction-associated steatohepatitis, or MASH. The final design, endpoints and patient population will depend on discussions with regulators. Management said either the WHO risk-drinking-level endpoint or zero-heavy-drinking-days endpoint could support approval by the FDA, while European regulators generally seek zero heavy drinking days as an endpoint along with WHO risk-drinking-level results as a key secondary measure.
Altimmune said pemvidutide has FDA Fast Track designation for AUD. Separately, the company expects to initiate its PERFORMA Phase III MASH trial during the third quarter and expects to announce completion of enrollment in its RESTORE Phase II alcohol-related liver disease trial during the same quarter.
About Altimmune (NASDAQ:ALT)
Altimmune, Inc is a clinical-stage biopharmaceutical company headquartered in Gaithersburg, Maryland, dedicated to the development of vaccines and immunotherapeutics. The company leverages proprietary technology platforms to create intranasal vaccine candidates and novel therapies targeting liver diseases and metabolic disorders. Altimmune’s approach emphasizes the stimulation of both systemic and mucosal immune responses to address unmet medical needs in infectious and chronic conditions.
Among its lead programs, NasoVAX is an investigational intranasal influenza vaccine designed to provide broad, long-lasting protection through a single, non-invasive dose.
