ORLANDO — A novel, investigational oral biologic for use in peanut allergy oral immunotherapy (OIT) met all primary endpoints, and demonstrated an acceptable safety profile, researchers reported here.
In the phase III trial, the median tolerated peanut protein dose improved 100-fold from study entry to exit in the AR101-treated patients, and symptom severity and epinephrine use at exit were blunted in these participants, according to Stacie Jones, MD, of the University of Arkansas and Arkansas Children’s Hospital in Little Rock, and colleagues.
Serious adverse events and withdrawals due to gastrointestinal or hypersensitivity events occurred in less than 5% of AR101, but one in five AR101 (n=76, 20.4%) withdrew during the study, compared with around 6% of patients in the placebo arm (percentage of patients completing study, 80% and 94%, respectively), they reported at the American Academy of Allergy, Asthma & Immunology and the World Allergy Organization meeting.
AR101 (Aimmune Therapeutics) could become the first approved treatment for peanut allergy OIT, pending FDA approval. The drug has been granted Fast Track Designation and Breakthrough Therapy Designation status by the FDA, and Aimmune plans to file a request to market AR101 in the U.S. by the end of 2018.
The international PALISADE study was conducted at 66 academic and individual practice centers. It included 554 patients, ages 4-17 years at enrollment, who were treated for approximately a year, followed by a double-blind, placebo-controlled food challenge.
The median tolerated dose of peanut protein at study entry was 10 mg (approximately 1/30 of a peanut), and 43% of patients had a peanut-specific IgE level >100 kU/L at baseline. Almost three in four participants in both treatment groups (72%) had a pre-study history of peanut anaphylaxis.
In this highly allergic population of children and teens with peanut allergies, 67% of AR101-treated patients successfully tolerated an exit food challenge, compared with 4% of patients treated with placebo (baseline tolerance ≤ 30 mg peanut protein; exit challenge = 600 mg peanut protein).
Also, approximately 99% of AR101-treated participants and 95% of placebo-treated patients had a treatment-emergent adverse event, but no deaths, life-threatening adverse events, or suspected unexpected serious adverse reactions occurred.
“The overall safety profile of AR101 was similar to previous studies of oral immunotherapy. Interestingly, the rate of withdrawal due to GI issues and a (single) case of eosinophilic esophagitis (EoE) was lower than expected,” Jones said.
Daniel C. Adelman, MD, Chief Medical Officer for Aimmune Therapeutics, told MedPage Today that an FDA ruling on the company’s application could come as early as the middle of 2019, with AR101 available for commercial use by the end of 2019.
Adelman said the OIT will be marketed to allergists/immunologists, but not to general practitioners.
“This is immunotherapy, and allergists are very comfortable managing the intricacies of allergy immunotherapy,” he said. “We believe that they are best equipped to deal with patients undergoing desensitization. We will also be reaching out to internists and general practitioners to make them aware of this therapy and explain the importance of referral to a qualified allergist.”
Adelman said the therapeutic goal is to prevent life-threatening reactions to accidental peanut exposure, but to simplify the lives of allergic patients and their families.
“The average accidental peanut exposure is around 100 mg, and we were able to demonstrate in our study that a large percentage of patients could tolerate 600 mg dose following this treatment,” he said. “That is the equivalent of over a gram of peanut.”
Greenhawt, who was not involved with the study, said the possible approval of not one but two commercially available peanut allergy OITs within the next several years would be a game changer for pediatric patients with the allergy and their families.
“When I was a fellow 10 or 11 years ago, we had nothing to offer these patients,” Greenhawt said. “Now, we may soon have two commercially available options to treat peanut allergies that both work exceptionally well and have very good safety profiles. The approval of these therapies cannot come fast enough.”
The study was funded by Aimmune Therapeutics. Some co-authors are company employees.
Jones disclosed a relevant relationship with Aimmume Therapeutics.