The AR101 oral therapy—a biologic designed to desensitize peanut allergies, manufactured by Aimmune Therapeutics—is anticipated to be submitted for FDA approval in the next month.
Jay Lieberman, MD
A long-term cohort assessment of an oral immunotherapy has evidenced the investigative drug’s potential to become the first therapy approved to treat patients with peanut allergies.
The AR101 oral therapy—a biologic designed to desensitize peanut allergies, manufactured by Aimmune Therapeutics—is anticipated to be submitted for US Food and Drug Administration (FDA) approval in the next month. Its application will include the results of the phase 3 PALISADES trial, originally presented at the American College of Allergy, Asthma, and Immunology (ACAAI) annual meeting in Seattle, WA, this week.
Investigators screened patients 4-55 years old with peanut allergies to assess allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein in a double-blind, placebo-controlled trial. The challenge dose of 100 mg approximates to one-third of a peanut kernel, investigators noted.
They randomized 551 patients 3:1 to either AR101 or placebo on an escalating-dose regimen. Participants to complete the regimen of 300 mg daily maintenance therapy for about 24 weeks then underwent a double-blind, placebo-controlled food challenge at the end of the trial. Investigators set a primary efficacy endpoint as the proportion of patients 4-17 years old who could ingest a challenge dose of 600 mg peanut or more without dose-limiting symptoms.
Among the patient population, 496 (90%) were aged 4-17 years. Treatment groups were split 372 to AR101, and 124 to placebo.
During the food challenge exit trial, 250 (67.2%) of patients to receive the oral therapy were capable of ingesting 600-plus mg peanut protein without dose-limiting symptoms—compared to just 5 (4%) of patients to receive placebo, distinguishing a difference of 63.2 percentage points (95% CI: 53.0 — 73.3; P < .001).
In assessing for maximum severity of symptoms across the 2 treatment arms, patients administered placebo fared worse. Symptom severity was moderate in 59% of the placebo patients, and severe in 11%, while just 25% and 5% of AR101 patients, respectively, reported moderate and severe maximum symptoms.
However, adverse events were prevalent in more than 95% of the participants aged 4-17 years. In pediatric and adolescent patients administered AR101, 34.7% reported mild events, 59.7% reported moderate events, and 4.3% reported severe events. The rates for the placebo group were 50%, 44.4%, and 0.8%, respectively. Investigative drug efficacy was not shown in participants aged 18 years or older.
Investigators concluded that participants—comprised of patients highly allergic to peanuts—were capable of greater exposure to peanut protein when administered the daily therapy.
“Desensitization was evaluated after 6 months of the maintenance regimen, which limits the conclusions that can be drawn regarding long-term safety and efficacy after years of use, which would be necessary in the clinical treatment of patients, given that food allergen immunotherapy is generally not considered to be a curative treatment,” they concluded.
Allergist Jay Lieberman, MD, study co-author and vice chair of the ACAAI Food Allergy Committee, noted a couple of obvious limitations to the potential therapy: it’s not a quick-fix drug, and it doesn’t inhibit patients to eat peanuts whenever they’d like.
“But it is definitely a breakthrough,” Lieberman said. “The hope would be to have a treatment available in the second half of 2019. If that happens, people who receive and are able to tolerate this treatment should be protected from accidental exposures.”
Fellow allergist, co-author, and past ACAAI president Stephen Tilles, MD, added he was pleased to find two-thirds of treated patients were able to tolerate the equivalent of 2 peanuts daily, and half were able to tolerate 4. It was a significant jump from their original hope of immunizing patients enough to be able to tolerate 1-2 peanuts daily.
“We’re excited about the potential to help children and adolescents with peanut allergy protect themselves against accidentally eating a food with peanut in it,” Tilles said.
The excitement is likely shared among most of the allergy community, as they await Aimmune’s FDA drug application submission prior to 2019.
The study, "AR101 Oral Immunotherapy for Peanut Allergy," was presented at ACAAI 2018 and published in the New England Journal of Medicine.
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