Food allergies are a significant and growing health problem in the United States, Europe and throughout the developed world. It is estimated that more than 30 million people in the United States and Europe have a food allergy, and more than five million people in the United States and Europe have peanut allergy, including more than two million children. Peanut allergies present a potentially life-threatening, chronic condition for which there are no approved treatments.
What if a proprietary formulation of peanut flour and pharmaceutical-grade ingredients could impart immunity to a peanut allergy, or at least to accidental exposure to peanuts?
Bouyed by success in earlier rounds of FDA testing, Aimmune Therapeutics, Inc. (NADSAQ: AIMT) announced earlier today that it has enrolled the first patient in the pivotal Phase 3 PALISADE trial of its lead product candidate, AR101 for the treatment of peanut allergy. Previously, the Food and Drug Administration (FDA) has granted AR101 Breakthrough Therapy Designation status, and in September 2014 the FDA gave AR101 fast track designation even before Phase 2 clinical data was available.
PALISADE, which is an acronym for Peanut ALlergy oral Immunotherapy Study of AR101 for DEsensitization in children and adults, is an international, randomized 3:1, double-blind, placebo-controlled, Phase 3 trial of the efficacy and safety of AR101 in a characterized desensitization approach in patients with peanut allergy. Aimmune expects PALISADE to enroll approximately 500 peanut-allergic patients 4-55 years of age at more than 60 clinical sites in the United States, Canada, and nine countries in the European Union. Aimmune expects to complete enrollment in PALISADE in the second half of 2016 and complete the trial in the second half of 2017.
PALISADE will evaluate the safety and efficacy of AR101 for desensitizing peanut-allergic patients to a level sufficient to reliably protect them from allergic reactions upon accidental exposures to peanut. Under the PALISADE protocol, patients will undergo a dose escalation period of approximately 22 weeks to reach the maintenance dose of 300 mg per day, then continue with daily maintenance at 300 mg per day for approximately six months. At the end of the maintenance period, patients will undergo an exit double-blind, placebo-controlled food challenge (DBPCFC).
Aimmune Therapeutics recently received U.S. Patent No. 9,198,869, issued on December 1, 2015, for a method of manufacturing peanut formulations for oral desensitization.
The ‘869 patent explains the need for a peanut allergy treatment, explaining that the current state of the art is simply diet avoidance, which is far from foolproof. Further, only 20% of those with a peanut allergy can be expected to outgrow the allergy. The patent Backround explains:
During the past decade, much has been learned about allergens in peanut. Peanuts are commonly associated with severe reactions, including life threatening anaphylaxis. The current standard of care in management of food allergy is dietary avoidance of the food and education of the subject/family in the acute management of an allergic reaction. The burden of avoidance and constant fear of accidental exposure negatively impacts the health-related quality of life for both subjects and their families. Quality of life surveys indicate that families with children having food allergies have significant impact on food preparation, social activities, finding appropriate childcare, school attendance, and level of stress among other things.
Currently, the only treatment for peanut allergy is a peanut-free diet and ready access to self-injectable epinephrine. However, strict avoidance diets can be complicated due to difficulty in interpreting labels and by the presence of undeclared or hidden allergens in commercially prepared foods. Accidental ingestions are unfortunately common, with up to 50% of food-allergic subjects having an allergic reaction over a two-year period. Allergic reactions to peanut can be severe and life threatening; and peanut and/or tree nut allergies account for the vast majority of fatal food-induced anaphylaxis. This combination of strict avoidance diets, the high incidence of accidental exposures, and the risk of severe or even fatal reactions with accidental exposures adds a tremendous burden and stress on subjects and their families. Further complicating matters is the fact that only about 20% of children will outgrow peanut allergy, meaning that the majority of people with peanut allergy will have it for the rest of their lives. If we couple the rising prevalence and increased consumption of peanut in Western countries with the facts that only approximately 1 in 5 will outgrow their allergy, that allergic reactions have the potential to be severe or even fatal, and that accidental exposures are common, developing an effective treatment for peanut allergy becomes even more imperative.
PALISADE’s primary endpoint is toleration of a cumulative amount of 1,043 mg of peanut protein in the exit DBPCFC. PALISADE’s inclusion criteria allow for baseline toleration of a cumulative amount not exceeding 44 mg of peanut protein in an entry DBPCFC. In Aimmune’s ARC001 Phase 2 study of AR101, where the inclusion criteria allowed toleration of a cumulative amount of up to 44 mg of peanut protein, 78 percent of active-arm patients who completed the study’s 22-week up-dosing protocol (n=23) tolerated a cumulative amount of 1,043 mg of peanut protein in the exit DBPCFC. Furthermore, in that study, 100 percent of active-arm patients who completed the study tolerated a cumulative amount of 443 mg of peanut protein, a level that is a secondary endpoint for PALISADE. As a typical peanut kernel contains approximately 250-300 mg of peanut protein, Aimmune believes PALISADE patients who receive treatment with AR101 and continue with maintenance dosing will be reliably protected to clinically meaningful levels of accidental peanut exposure.