Obesity dropouts hurt Altimmune
The company’s value is cut in half as mid-stage data prove a let-down.
Last month Altimmune said it was looking for weight loss of 8-10% with its obesity project pemvidutide, and today’s interim data from the Momentum trial reveal that it hit that target pretty much on the nose. What Altimmune was emphatically not looking for was nearly a quarter of the patients in the high-dose group dropping out because of side effects.
This makes the GLP-1/glucagon agonist appear notably more toxic than both Novo’s Wegovy and Lilly’s Mounjaro. There are reasons to believe that the picture might not be quite as bleak as it seems, but so far Altimmune’s investors have not been swayed by these: the group’s shares were down 53% in early trading.
The highest dose tested in Altimmune’s phase 2 Momentum trial, 2.4mg, caused mean placebo-adjusted weight loss of 9.7%, a respectable figure at the 24-week time point. But adverse event rates were high, and the eye-catching discontinuation rate at this dose – 24.2%, placebo adjusted – compares poorly with the phase 3 obesity trials of Wegovy and Mounjaro.
|Obesity cross-trial comparison|
|Trial||Step 1 (Ph3, NCT03548935)||Surmount-1 (Ph3, NCT04184622)||Momentum (Ph2, NCT05295875)|
|Project and dose||Wegovy 2.4mg||Mounjaro 15mg
|Pemvidutide 1.2mg||Pemvidutide 1.8mg||Pemvidutide 2.4mg|
|Pbo-adj weight loss at 24wk (% points)||~9||~12||6.3||8.4||9.7|
|Safety (all pbo-adj)|
|Nausea (% points)||28.0||21.5||14.9||49.9||46.2|
|Diarrhoea (% points)||14.0||15.7||2.4||-0.1||9.6|
|Vomiting (% points)||18.0||10.5||5.0||15.0||24.4|
|Constipation (% points)||13.0||5.9||7.5||2.5||12.2|
|Discontinuations due to adverse events (% points)||3.6||3.6||4.9||7.4||24.2|
|AE data at 68wks for Wegovy, 72wks for Mounjaro and 24wks for pemvidutide. Source: company releases, FDA, NEJM.|
On a call today, Altimmune’s management sought to play down the tolerability issues. The group pointed out that the discontinuation rate was similar to that seen with Mounjaro in its phase 2 diabetes trial – here, 25% of the patients given the highest 15mg dose dropped out owing to adverse events.
Altimmune contended that the only reason discontinuation rates were lower in Wegovy and Mounjaro’s pivotal trials was because those studies allowed dose reduction should tolerability prove an issue, whereas Momentum did not. Allowing dose reduction in phase 3 trials of pemvidutide is one of the strategies Altimmune is considering.
Another is using higher doses and longer titration periods. New patients receiving either Wegovy or Mounjaro must have their doses slowly adjusted upwards over a period of four to five months, something primary care physicians find difficult to oversee. Altimmune had hoped that pemvidutide could be given without a run-in period, or at least with a much shorter one, thereby gaining a sizeable advantage over Novo and Lilly’s drugs.
Altimmune has now more or less admitted that this dream is dead, at least for the high dose. But if titration is necessary anyway to sidestep toxicity, perhaps even higher dosing might be possible, they said. The result, theoretically, could be that the weight loss seen with pemvidutide in phase 3 ultimately exceeds that seen with Wegovy and Mounjaro.
This seems somewhat optimistic, although the group is convinced that pushing into phase 3 is the correct decision. It intends to finalise its plans before the full 48-week Momentum readout, due towards the end of this year. But competing with Wegovy and Mounjaro already looked like a tough task, and unless pemvidutide’s tolerability improves sharply in phase 3 it may prove impossible.