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Altimmune (NASDAQ:ALT) has had a tumultuous 2023, falling precipitously in March and then climbing rapidly back starting early December. In March last year, it fell after Pemvidutide produced poor weight loss data from a phase 2 trial called MOMENTUM which enrolled 320 patients who were obese or overweight but did not have diabetes. Data from 160 patients at 24 weeks showed average weight loss of 7.3%, 9.4% and 10.7% at the 1.2 mg, 1.8 mg, and 2.4 mg doses respectively, with the placebo group seeing a mean weight loss of 1.0%. This data was fine compared to semaglutide, but what killed it for Altimmune was the very high discontinuation rate seen here [interestingly, the DCR was also very high in placebo]. Like I noted before:
Treatment discontinuation rates were 28.2% in people on placebo, majority of which were due to withdrawal of consent; while 24.0% in patients on Pemvidutide, half of which were attributed to GI AEs, as per Altimmune.
In that earlier article, I compared Pemvidutide with both semaglutide and Lilly’s weight loss drug Tirzepatide, and we saw how in both DCR and weight loss, these drugs performed much better than Pemvidutide. That summed up the situation for me then: Altimmune is a story of too little, too late.
In December, however, a second look at the MOMENTUM trial – this time as the trial toplined – painted a different picture for the drug. Not only was the mean weight loss now at par with rival drugs, but there was now considerable differentiation between the DCR rates of drug versus placebo arm. The DCR rate per se was still pretty high, but I think the comparative difference between drug versus placebo arms is a more reasonable metric than the per se rate.
Here’s the data:
At the 2.4 mg dose — the highest tested — mean weight loss of 15.6% was seen at week 48. More than 30% of patients in this cohort achieved at least 20% weight loss.
Results further showed that greater weight loss was seen with higher doses of the peptide-based GLP-1/glucagon dual receptor agonist.
The MOMENTUM trial enrolled ~400 individuals with a mean age of 50, mean body mass index (BMI) of ~37 kg/m2 (~81.6 lb/m2 ) and mean body weight of approximately 104 kg (~229 lb). Nearly three out of four subjects were female.
About 74% of pemvidutide patients finished the trial. compared to 61.9% of placebo subjects. There was one drug-related serious adverse event, which was vomiting at the 2.4 mg dose.
Altimmune CEO Vipin Garg noted that the 15.6% mean weight loss with the 2.4 mg dose was associated with a mean weight loss of 32.2 lbs at 48 weeks and 48% of those on the 2.4 mg dose with baseline obesity no longer had obesity by the end of the study.
Here, we have a mean weight loss figure of 15.6% at week 48, and DCR rates of 26% in the drug arm versus 38.1% in the placebo arm. If you go back and compare the mean weight loss numbers of the rival drugs I cited, you can see that this data is at par with, if not better than, their numbers.
As JMP noted:
Pemvidutide has a competitive profile based on the top-line MOMENTUM data with greater weight loss than semaglutide (Wegovy), better lipid changes and tolerability than tirzepatide (Zepbound), and better cardiac safety than retatrutide.
Remember that this data is at 48 weeks and there has been substantial improvement seen from 24 weeks. Weight loss figures, in my brief experience, are additive across duration – meaning, unlike, say, oncology drugs, if you take weight loss drugs for a longer duration, you get better results than if you took them for a shorter duration. Now, here are some rival figures at different durations:
Zepbound – 22% reduction at week 72
Wegovy – 15.6% reduction at week 68.
Pemvidutide – 15.6% BUT at week 48.
Clearly, there may be a reasonable hope for further improvement if the durations are normalized. Thus, on the weight loss front, Pemvidutide is at least at par with its major rivals.
Altimmune’s trump card is lipid reduction and lower cv risks. As the company pointed out in their earnings call:
…at the 24-week time point, the magnitude of LDL cholesterol reduction on pemvidutide treatment with several fall better than that achieved by semaglutide or tirzepatide in a similar population at the conclusion of their trials, but at 68 and 72 weeks, respectively.
We believe that it is the action of the glucagon receptor agonism present in pemvidutide, but not in semaglutide or tirzepatide that leads to the improved effects on lipids and differentiates pemvidutide. The important reductions in lipid-based cardiovascular risk factors suggest that pemvidutide has the potential to achieve even greater reductions in cardiovascular risk than those observed in the recently completed select cardiovascular outcomes trial.
Of important note, pemvidutide has not been associated with minimal heart rate increases in any of our trials to date. By contrast, other GLP-1-based multi agonist containing glucagon, have been associated with these increases and in one case, arrhythmias. This may prove to be an important differentiator as cardiac effects may be — may not be tolerated in a population with higher cardiovascular risk, such as elderly individuals or individuals with pre-existing cardiovascular disease.
Contrast that with data from those other two molecules. While at week 48, pemvidutide saw LDL cholesterol reduction of 11.2% for the 1.8-mg dose and 9.9% for the 2.4-mg dose, Zepbound saw a 7.1% reduction at week 72 and wegovy had a 2.5% reduction at week 68.
Treatment related adverse events still caused a high DCR in pemvidutide compared to those other two drugs. For the two highest doses, DCR from TEAEs stood at 16.2% and 15.5% for pemvidutide, while with Zepbound and wegovy, the rates were 6.7% and 6.8% at the highest dose.
It should be kept in mind that, however, that both Eli Lilly (LLY) and Novo allowed dose titration as well as dose reductions in cases of AEs in their phase 3 trials, data from which I have used here. In Altimmune’s case, no dose titration was allowed for the 1.2 mg and 1.8mg doses, and only a four week titration was allowed for the 2.4mg dose. No dose reductions were allowed at all if a patient experienced tolerability problems. Management thinks that once they allow these in their phase 3 trials, the DCR rate will fall to single digit figures just like with its larger rivals. How much effect that will have on the weight loss figures remains to be seen.
In other good news for Altimmune, Pfizer (PFE) discontinued trials for the twice daily program of its own weight loss drug Danuglipron, citing side effects. Also, Roche (OTCQX:RHHBY) (OTCQX:RHHBF) purchased Carmot for $2.7bn for its dual GLP-1/GIP agonist. This sort of market consolidation is good news for Altimmune, which remains among the few smallcap players in a space increasingly taken over by mega pharma.
Financials
ALT has a market cap of $600mn and a cash balance of $140mn. Research and development expenses were $18.4 million for the three months ended September 30, 2023, while general and administrative expenses were $4.5 million. At that rate, they have cash for maybe 6 more quarters, and will need more cash to fund later stage developments. I am surprised the company did not try to raise funds in December after the positive data took the stock up.
Bottomline
ALT is in an excellent position right now. I will be asked: why didn’t I buy it when it was trading at $2? I will tell them that I don’t have a crystal ball, so I cannot buy a stock with poor or no data, which is where we were before December. Now, with this data, the stock is thoroughly derisked as far as efficacy is concerned, but is still at a low valuation compared to the huge market potential of a successful weight loss drug. For comparison, wegovy generated nearly $4bn in revenue for Novo in 2023. Given that pemvidutide performed better than wegovy in many metrics, its current valuation is wrong, and I expect considerable upside from here, all things being equal.
