Aimmune just got one up on its rival DBV Technologies in the race to get a peanut allergy project approved with a win in the Palisade trial of its oral candidate AR101.
However, while DBV’s stock was down as much as 5% today, Aimmune also fell 6% this morning on doubts about safety and patient compliance, wiping out an initial 7% gain on early excitement about the Palisade data. If both projects make it to the market it might be a case of weighing up their relative efficacies against side effects.
Still, there are major doubts about whether DBV will even get approved after its patch, Viaskin Peanut, failed its pivotal Pepites trial (DBV’s peanut problems open the door for Aimmune, October 23, 2017).
Aimmune had no such problem, with Palisade meeting its primary endpoint; 67% of patients in the AR101 group could tolerate a highest dose of peanut protein of 600mg, equivalent to two peanuts, versus 4% in the placebo group, which was significant with a p value of 0.00001.
In addition, the lower bound of the confidence interval exceeded the pre-specified 15% threshold, which is where Pepites fell short. DBV has pushed on regardless, last week claiming that the FDA would accept its existing data package – however, whether the agency will actually approve Viaskin Peanut is another question.
If it does, DBV will no doubt hope to position Viaskin Peanut before AR101 in the treatment cascade as a more benign option. 20% of patients in Palisade discontinued, versus 10% in DBV’s Pepites trial.
Of the 76 Palisade dropouts, 30 patients left the study because of adverse events, and there were seven cases of anaphylaxis, one of which was classified as severe required epinephrine and overnight hospitalisation.
There was also one case of eosinophilic oesophagitis. Aimmune executives said there was no evidence linking this with AR101, but these issues still served to spook investors – as well as perhaps an element of selling on good news. Leerink analysts also pointed to Palisade's burdensome up-titration phase as a possible reason for dropouts.
Aimmune plans to present full data from Palisade at the AAAAI meeting in Orlando in March, and should file AR101 in the US, where it has breakthrough designation, in late 2018.
A filing in Europe will follow in the first half of next year based on the Artemis trial, which has a more stringent primary endpoint, with patients required to tolerate 1,000mg of peanut protein.
While Aimmune’s data look good enough for approval, one criticism of both AR101 and Viaskin Peanut is that trials have not evaluated measures of anaphylactic shock, for example hospitalisations or Epipen use.
Interestingly, Aimmune’s chief medical officer, Dan Adelman, said during a conference call today that during the final food challenge in Palisade there were only nine uses of epinephrine in the AR101 group, while 50% of those in the placebo group needed epinephrine.
Another peanut allergy project, Anaptysbio’s ANB020, is also due to yield phase IIa results this quarter. This could soon be a crowded space, and long-term data might be needed before a clear winner emerges. Crunch time is coming for both DBV and Aimmune.
|Arc004 (Palisade follow-on)||NCT02993107|