Tiny Altimmune is slinging stones at the goliaths of the obesity market. Facing well-set incumbents, the biotech pitched its midphase data as evidence that its GLP-1 candidate can carve out a niche in obesity patients at risk of cardiovascular events—but tolerability issues that marred an earlier data drop remain.
The data come from a phase 2 trial of pemvidutide, Altimmune’s GLP-1/glucagon dual receptor agonist. Altimmune randomized 391 subjects who have obesity or are overweight with at least one comorbidity, excluding diabetes, to receive one of three doses of pemvidutide or placebo. An earlier 24-week analysis suggested pemvidutide’s efficacy may land in between that of Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound.
The 48-week analysis reinforces the impression that weight loss linked to pemvidutide falls in the same ballpark as Wegovy and Zepbound without scaling the heights reached by Lilly’s drug. At the highest dose, 2.4 mg, participants had a mean weight loss of 15.6%. Weight loss in the placebo arm was 2.2%.
To put that figure in context, the highest dose of Zepbound had blown past 15.6% weight loss by week 48 on its way to a 22% reduction (PDF) at week 72 of a trial in a similar patient population. Pemvidutide may have a slight edge on Wegovy, with the caveat that cross-trial comparisons can be unreliable if subjects kick on from here. Weight loss at week 68 of a comparable Wegovy study was (PDF) 15.6%.
The pemvidutide weight loss matches the mid-teens reduction that Altimmune set as its target for the 48-week analysis on a quarterly results conference call with investors last month. But with Wegovy and Zepbound already on the market, and pemvidutide just clearing phase 2, Altimmune will likely need to offer something beyond competitive efficacy to make a dent on the market.
Altimmune’s management has identified cardiovascular safety as that something. The 24-week analysis suggested pemvidutide may drive deeper declines in LDL cholesterol than its approved rivals, an effect that Scott Harris, chief medical officer at Altimmune, attributed to “the action of the glucagon receptor agonism present in pemvidutide, but not in semaglutide or tirzepatide.”
At week 48, LDL cholesterol had fallen 11.2% for the 1.8-mg dose and 9.9% for the 2.4-mg dose. The data compare favorably to the 7.1% reduction seen at week 72 of Lilly’s study and the 2.5% reduction at week 68 of Novo’s trial.
Altimmune sees cardiac safety as a related advantage. In the 48-week analysis, no patients in its trial suffered major adverse cardiac events. The rate of cardiac adverse events including arrhythmias was the same across the placebo and pemvidutide cohorts. Harris told investors cardiac safety may be an “important differentiator.”
“Cardiac effects may not be tolerated in a population with higher cardiovascular risk, such as elderly individuals or individuals with pre-existing cardiovascular disease. We see the obesity marketplace is becoming highly segmented based on the different patient needs and profiles, with pemvidutide fulfilling the need for the large segment with elevated lipids or liver fat content, which we estimate to be approximately 70% of the obesity marketplace,” the CMO said last month.
However, other aspects of Altimmune’s safety data look weak compared to Wegovy and Zepbound. The rates of drug-related adverse events leading to discontinuation were 16.2% and 15.5% in the two top dose cohorts of the pemvidutide trial. Across both Zepbound trials, the rate was 6.7% at the top dose. The rate for Wegovy was 6.8%.
Nausea was more common in the pemvidutide study too, particularly compared to Zepbound. At the two highest pemvidutide doses, 59% and 50% of patients reported nausea. That compares to a maximum rate of 29% for Zepbound and 44% for Wegovy. Lilly and Novo titrated the dose, and allowed dose reduction, in their phase 3 trials.
There was no dose titration at the two lower pemvidutide doses, only a four-week titration at the top dose and no option for patients who experienced tolerability problems to drop down to a lower dose. On a call to discuss the latest data, Harris said that “by allowing dose reduction in the phase 3 program, we expect the discontinuation rates to drop down to single digits as they have in other phase 3 programs.”
Investors partly looked past tolerability concerns this time around, sending Altimmune’s share price up 50% to $4.74 after hours. The increase made up some of the losses Altimmune suffered when the 24-week data was released, which sent its stock tumbling from above $10 to below $5.