Aimmune's Peanut Allergy Product Hits Primary Endpoints in European Phase III Trial
In November 2018, the company had announced the publication of its successful Phase III PALISADE clinical trial of AR101 in the New England Journal of Medicine (NEJM).
AR101 is 12 percent defatted peanut flower using a Good Manufacturing Process (GMP). The idea is that by exposing people, usually children, who are allergic to peanuts, to AR101 under controlled circumstances, they can be desensitized to the allergen. About 2.5 percent off all children in the U.S. might have a peanut allergy, and according to the American College of Allergy, Asthma and Immunology, the incidence of peanut allergies in children in the U.S. has risen 21 percent since 2010.
The European clinical trial, ARTEMIS, enrolled 175 children and adolescents ages 4 to 17 from 18 sites in France, Germany, Ireland, Italy, Spain, Sweden and the UK. They went through about six months of dose escalation and then three months of a daily therapeutic dose of AR101 at 300 mg or placebo. This was followed by an exit double-blind, placebo-controlled food challenge. In other words, they were fed a peanut or peanut product to see how they reacted.
The primary efficacy endpoint was the patients’ ability to tolerate a 1,000-mg single dose of peanut protein, the equivalent of about three to four peanut kernels.
The median tolerated dose of peanut protein for patients receiving AR101 improved 100-fold, from 10 mg at baseline to 1,000 mg at exit. No cases of anaphylaxis or of eosinophilic esophagitis (EoE) were observed.
“We are very pleased with the results of the ARTEMIS trial, which demonstrate that AR101 significantly improved the ability of patients to tolerate the 1,000-mg dose of peanut protein in the exit food challenge, which correlates to at least three or four peanuts,” stated Jayson Dallas, Aimmune’s president and chief executive officer. “This level of protection provides ample buffer beyond a typical bite of a peanut-containing food in the real world.”
Based on the ARTEMIS results, Aimmune plans to submit a marketing authorization application (MAA) for AR101 to the European Medicines Agency (EMA) in mid-2019. Its biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) was submitted in December 2018 but was delayed by the government closure until January 2019. The BLA is being reviewed in the U.S. under a 12-month target review period, so the target action date is late January 2020 in the U.S.
There was some confusion between Aimmune and the FDA, at least some of which was related to the U.S. government shutdown. On March 1, 2019, BioPharmaDive noted that the FDA did not consider the treatment to be covered by user fee agreements that typically regulate most drug reviews. But when Aimmune submitted the BLA in December, it thought it did. Then the 35-day government shutdown added to the confusion.
BioPharmaDive wrote, “During the shutdown, the FDA continued to review any drugs for which it had received user fees and which were covered by Prescription Drug Users Fee Act agreements between industry and the regulator. Having submitted AR101 and paid its user fee on Dec 21, Aimmune expected its peanut allergy treatment would fall in that category. The FDA, however, disagreed and determined initially that AR101 was exempt from PDUFA, Aimmune said … likely due to it being an allergenic product.”
Which is why there’s a 12-month review date instead of the standard 10-month review. In a March statement, Aimmune indicated it is continuing discussions with the FDA over “the apparent lack of precedent for the FDA reviewing a BLA for a PDUFA-exempt product candidate that has Breakthrough Therapy designation.”
However, on March 18, the FDA accepted the BLA and gave it a 12-month timeline, with a target action date of late January 2020.
In the PALISADE study, conducted in the U.S., AR101 had a favorable safety profile, but there were adverse side effects in more than 95 percent of patients in both trial groups, nearly all of them mild or moderate in severity. However, 2.4 percent had severe adverse events and 1.1 percent experienced serious adverse events. Two patients required the use of epinephrine due to severe adverse events. About 11.6 percent of patients dropped out of the study because of the side effects, compared to 2.4 percent in the placebo group.