In documents released Wednesday ahead of an FDA advisory panel meeting on September 13, reviewers highlighted safety issues observed in clinical studies of Aimmune Therapeutics' peanut allergy desensitisation treatment AR101. Agency staff noted that the experimental oral immunotherapy, which Aimmune proposes to market as Palforzia, was associated with higher rates of treatment discontinuation, systemic allergic reactions and reports of eosinophilic esophagitis compared to placebo despite both groups following a peanut avoidance diet. However, shares in the company rose more than 10% as reviewers backed the efficacy of AR101.
Aimmune's filing for AR101 was backed by data from five Phase III studies as well as two mid-stage trials. Results from the Phase III PALISADE study, also known as ARC003, showed that 67.2% of children aged four to 17 years who received AR101 could tolerate challenge with a single dose of at least 600 mg of peanut protein with no more than mild symptoms after one year of treatment, versus 4% of those in the placebo arm.
In regards to adverse events that occurred during the study programme, agency staff noted that 9.4% of patients taking AR101 experienced systemic allergic reactions during initial dose escalation and up-dosing combined, versus 3.8% for placebo. In the maintenance phase, 8.7% AR101 recipients and 1.7% of those on placebo reported systemic allergic reactions. Reviewers also pointed out that during initial dose escalation and up-dosing, 1.6% of subjects given AR101 discontinued due to systemic allergic reactions, versus none in the placebo group, while discontinuation rates for both groups were 0.6% during maintenance. In addition, 12 subjects in the clinical programme developed eosinophilic esophagitis, compared to none for those taking placebo.
Stifel analyst Derek Archila has suggested that a positive vote could boost shares of Aimmune by 30%, while a negative vote could cut their value by half. "The FDA is really going to be charged with whether it can get comfortable with the longer-term safety," remarked Archila, adding "the crux of the [advisory panel meeting] will be if there is a need for longer-term safety data to really understand if you're putting these kids at undue risk by giving them the allergen they're allergic to."
The FDA accepted Aimmune's submission seeking approval of AR101 in March and indicated that its decision could come by late January 2020. Aimmune revealed earlier this year that the agency's review of the therapy had been delayed by a US government shutdown. AR101 is also under review in Europe.
Meanwhile, the Institute for Clinical and Economic Review (ICER) concluded in July that the "long-term benefits of desensitisation outweigh short-term risks." At the time, Aimmune said "ICER fails to incorporate available data on both long-term outcomes and quality of life," while Piper Jaffray analyst Christopher Raymond criticised the report as "yet another example of ICER's inherent bias against any novel therapy." For related analysis, see ViewPoints: ICER report suggests Aimmune has work to do.
Last month, DBV Technologies submitted an application for its Viaskin Peanut patch for peanut-allergic children ages four to 11 years after the FDA had previously requested additional data.
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