- A clinical study of peanut allergy patients found a significantly higher proportion could ingest 600 mg or more of peanut protein after taking an investigational medicine from Aimmune Therapeutics compared to those on placebo, according to data published Sunday in the New England Journal of Medicine.
- Of the 372 patients who received Aimmune's AR101, 250 — or 67% — were able to swallow that much peanut protein during an exit food challenge. Conversely, 4% of the 124 patients who received placebo were able to do the same. All of these patients were ages four to 17; an additional 55 adult patients were enrolled and given at least one dose of AR101 or placebo, but efficacy wasn't shown in that cohort.
- On safety, nearly all of the children experienced some level of adverse event during the study's intervention period. Mild events affected a smaller portion of the investigational arm versus the placebo arm, while the opposite was true of moderate and severe events. The AR-101 group also saw more patient dropouts, at 43 versus the placebo group's three, with gastrointestinal symptoms being a main cause.
The biotech plans to submit marketing applications for AR101 to U.S. regulators in December and European regulators some time in the middle of 2019, according to a Nov. 18 statement. Approvals will hinge on data from the Phase 3 PALISADE trial.
While the drug's efficacy appears undeniable, besting placebo on the measure of peanut protein tolerance, its safety profile will undoubtedly face thorough inspection.
In PALISADE's active-drug group, for instance, there were higher incidences of adverse events affecting respiratory tract, skin, immune system and — perhaps most notably — the gastrointestinal tract. Of the 43 AR101-treated patients who dropped out of the study, 16 did so because of chronic or recurrent dose-limiting gastrointestinal symptoms.
"This was a clinical trial that had a defined regimen. In the real world, I believe that allergists are going to adjust the up-dosing rate on an individual basis based on patient needs," said Daniel Adelman, Aimmune's chief medical officer, on a Nov. 18 investor call.
"So if a patient is having some mild gastrointestial discomfort , first of all antihistamines will be used to prophylax, and the physician may decide to slow down the up-dosing regimen. I believe that all of these measures are going to result in actually a lower discontinuation rate once the drug is available commercially," Adelman added.
Aside from the higher dropout rate, AR101-treated patients saw a higher rate of systemic allergic reaction than placebo: at 14% and 3%, respectively. Investigators also had to administer epinephrine to a larger portion of patients in the active-drug arm versus the placebo arm, though that's excluding the food exit challenges . During those challenges, 10% of the participants in the active-drug group and 53% in the placebo group received rescue epinephrine.
Aimmune executives noted that just one patient on AR101 therapy experienced a serious case of anaphylaxis.
Though investors may focus on the epinephrine use, AR101's risk-benefit profile appears favorable all things considered, and should experience uptake if approved, according to investment bank Credit Suisse.
"Physicians we have spoken to remain very comfortable with the AR101's safety profile and how they will incorporate the product into their practice," analyst Vamil Divan wrote in a Nov. 18 note.
Shareholders seem less sure, however. While Aimmune stock was up in pre-market and early morning trading, it backtracked later in the morning to sit around $28 per share — a more than 5% decline from Friday.