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New findings from the phase 3 PALISADE and ARTEMIS trials show more than half of treated patients could tolerate 1000 mg peanut protein in a post-care food challenge.
Ellen R. Sher, MD
New results from the phase 3 PALISADE and ARTEMIS studies assessing investigative oral biologic immunotherapy AR101 show the therapy has consistent efficacy and safety across a varied peanut allergy patient population.
The study comparison data, presented at the American College of Allergy, Asthma & Immunology (ACAAI) 2019 Scientific Meeting in Houston, showed the peanut protein therapy provided a clinically meaningful tolerance to allergen in more patients than placebo in a double-blind, placebo-controlled food challenge at the trial’s end.
Investigators, led by Ellen R. Sher, MD, allergist and immunologist with Allergy Partners of New Jersey, also reported a similar overall safety profile across the 2 patient populations, with a decreased adverse event frequency in patients administered a fixed dose of therapy, compared to the dose-escalation period.
The findings come during a period when Aimmune Therapeutic’s Biologics License Application (BLA) for AR101 is being reviewed by the US Food and Drug Adminsitration (FDA), which had previously granted the biologic a Breakthrough Therapy Designation for the desensitization of peanut-allergic patients aged 4-17 years old.
In an Allergenic Products Advisory Committee (APAC) meeting in September, the panel voted 7-2 in favor of the company’s efficacy and safety data used to support the therapy BLA. The FDA will decide on the application by January 2020.
The Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization (PALISADE) trial is a phase 3, international, randomized, double-blind, placebo controlled assessment including 496 patients aged 4-17 years old across 10 North American and European countries. Patients, including 55 adults aged 18-49 years old, were randomized 3:1 to either AR101 or placebo.
They underwent a dose escalation period of approximately 22 weeks to reach a therapeutic dose of 300 mg daily, for approximately 6 months. They then participated in an exit double-blind, placebo-controlled food challenge to test consecutive doses of 3, 10, 30, 100, 300, 600, and 1000 mg of peanut protein, given 20-30 minutes apart.
In the randomized, double-blind, placebo-controlled phase 3 AR101 Trial in Europe Measuring Oral Immunotherapy Success (ARTEMIS) trial, the efficacy and safety of the biologic was gauged in 175 peanut allergy patients aged 4-17 years across 7 European countries. Patients—who represented a highly-allergic population with a significant prevalence of comorbidities and reaction to low-dose peanut protein at an initial food challenge—were again randomized 3:1 to either AR101 or placebo.
They received an approximate six-month dose escalation, then 3 months of therapeutic dosing of AR101 300 mg daily, or placebo. The study’s primary endpoint was the patient’s ability to tolerate at least 1000 mg single-dose peanut protein without dose-limiting symptoms at the trial’s exit food challenge.
At the studies’ entry and exit food challenges, median patient tolerated dose had increased from 10 mg to 1000 mg, and about two-thirds of all patients tolerated at least 600 mg at their exit food challenge. More than 50% still tolerated 1000 mg.
Treatment emergent adverse events (TEAEs) observed during in-clinic dose escalation visits were generally shortly after dose administration, and were often resolved within 60 minutes. TEAEs frequency decreased in the therapeutic 300 mg daily AR101 dosing period, versus the dose escalation period.
Investigators also reported that 14% of patients in the PALISADE trial were administered epinephrine to treat TEAEs, compared to 6.8% of patients in ARTEMIS. They believe this disparity reflects allergy practice differences across the US and Europe, based on the different study populations.
That said, the similarities between the trials could provide critical insights for physicians on the clinical potential of AR101 in treated varied peanut-allergic patients, Sher noted. She said the physician-patient discussion and understanding of oral immunotherapy is critical toward providing tailored food allergy care.
“I’m encouraged to see that, across 2 robust and rigorously conducted clinical trials, the efficacy and safety of AR101 was consistent showing that treatment resulted in patients tolerating higher quantities of peanut protein while also confirming that the frequency of adverse events — while mostly mild or moderate – decreased during the therapeutic dosing period across both studies,” Sher said in a statement.