immune Therapeutics, Inc. announced that the results of its pivotal Phase 3 PALISADE trial of AR101 for the treatment of peanut allergy were presented today at the 2018 American Academy of Allergy, Asthma & Immunology–World Allergy Organization Joint Congress in Orlando.
PALISADE studied the efficacy and safety of AR101 in peanut-allergic patients by assessing reductions in clinical reactivity to peanut. In the primary analysis of patients ages 4–17, the trial met its primary and secondary endpoints, and AR101 demonstrated an encouraging tolerability and safety profile over the course of approximately one year of treatment. AR101 has U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation for peanut-allergic patients ages 4–17, and Aimmune plans to submit a Biologics License Application for AR101 by the end of 2018.
In late-breaking oral session 3609 at AAAAI-WAO, Stacie Jones, M.D., presented “Efficacy and Safety of AR101 in Peanut Allergy: Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial (PALISADE)” (Oral L6). Expanding on the topline results, today’s presentation included analyses of symptom severity in the exit double-blind, placebo-controlled food challenge (DBPCFC) and of immune modulation as measured by peanut-specific biomarkers (IgE and IgG4).
Dr. Jones, Professor and Chief of Pediatric Allergy and Immunology at the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, has been a principal investigator of the Consortium of Food Allergy Research (CoFAR), a program supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), since it was founded in 2005.
“Physicians, patients and their parents are eager for a treatment for peanut allergy, and this large-scale, multi-center study is a big step toward a potentially viable option,” said Dr. Jones. “In PALISADE, we were delighted to see a relatively low-maintenance dose yield not only impressive gains in the amount of peanut protein tolerated, but also a very manageable tolerability and safety profile. Families will be excited to see these results that provide hope for them for a possible future treatment They want the potential of protection, and even a lessening of symptoms, due to accidental exposures to peanut in the real world.”
“The results of our Phase 3 PALISADE trial exceeded our expectations. Now, with positive data in hand, we are excited to intensify our efforts to deliver potentially the first approved treatment for peanut allergy,” said Aimmune CEO Stephen Dilly, M.B.B.S., Ph.D. “To make this treatment a reality, we are working hard on all the activities necessary to submit our BLA around the end of this year, including completion of the RAMSES real-world trial. We’re also looking forward to completing further analyses of the PALISADE data as we continue to explore AR101’s effect on immune modulation and, where possible, correlate baseline patient characteristics, including peanut-specific IgE, to treatment outcomes. Again, we want to thank the investigators, patients and families who have made this progress possible.”
PALISADE enrolled a total of 554 patients ages 4-49. After approximately one year of treatment, patients completed an exit DBPCFC. In the trial’s primary analysis of ages 4–17, patients were highly atopic and highly sensitive to peanut. The median tolerated dose of peanut protein in the entry DBPCFC was 10 mg, the equivalent of approximately 1/30 of a peanut, and, at baseline, 43% of patients had a peanut-specific IgE level >100 kU/L. Furthermore, more than half of the study participants had been diagnosed with asthma, nearly two thirds had multiple food allergies, and almost three quarters reported a history of anaphylaxis.
In the primary analysis of ages 4–17, 296 patients (79.6%) from the AR101 arm completed the trial, compared to 116 patients (93.5%) from the placebo arm.
At an Aimmune-sponsored event the same day as the late-breaking oral presentation, an exploratory analysis showed that patients with baseline psIgE less than or equal to 100 kU/L tended to have more favorable outcomes than those with baseline psIgE above 100 kU/L. The lower peanut-specific IgE group had a higher overall completer rate, a higher response rate at the 1000-mg endpoint, fewer GI-related withdrawals, and no severe treatment-related adverse events.
There were no deaths or suspected, unexpected serious adverse reactions (SUSARs) in the trial, and the incidence of serious adverse events (SAEs) was low, as 1.1% of AR101 patients experienced SAEs that were possibly related to treatment. One AR101 patient (0.2%) experienced a severe SAE of anaphylaxis and withdrew from the trial; this patient had high peanut-specific IgE (>100 kU/L) at the start of the trial. There were no cases of anaphylactic shock observed in the trial.
Most AR101 patients (85.5%) did not experience any investigator-reported systemic hypersensitivity reactions (SHRs) during the trial. Among those (14.5%) who did, nearly all (98.2%) had mild or moderate reactions.
Aimmune expects to submit a Biologics License Application (BLA) for AR101 with the FDA by the end of 2018, followed by a Marketing Authorisation Application (MAA) with the European Medicines Agency (EMA) in the first half of 2019. In the United States, AR101 has FDA Fast Track Designation, as well as FDA Breakthrough Therapy Designation for peanut-allergic patients ages 4–17.
