Peanut-allergic children and adolescents treated with a peanut-derived oral immunotherapy drug have shown significant improvements in response to a challenge dose of peanut protein, according to data presented at the annual meeting of the American College of Allergy, Asthma, and Immunology.
A phase 3 placebo-controlled study, published simultaneously Nov. 18 in the New England Journal of Medicine, randomized 551 individuals with peanut allergy to receive an escalating dose of AR101 – an investigational peanut-derived biologic oral immunotherapy drug – ranging from 0.5-300 mg daily, or placebo.
After 12 months, 67.2% of the 372 participants aged 4-17 years who received the immunotherapy drug were able to eat a dose of 600 mg or more of peanut protein with only mild symptoms, compared with 4% of the 124 participants aged 4-17 years in the placebo group.
The secondary endpoints were whether participants could tolerate either a 300 mg or 1,000 mg dose in the exit food challenge. For the 300 mg dose, 76.6% of the immunotherapy group and 8.1% of the placebo group were able to tolerate it, and for the 1,000 mg group, 50.3% of the immunotherapy group were able to tolerate it, compared with 2.4% of the placebo group.
During the exit food challenge, the severity of symptoms was significantly higher in the placebo group than in the treatment group. One-quarter of participants in the treatment group had at most moderate symptoms, compared with 59% in the placebo group. However, severe symptoms were experienced by 11% of the placebo group, compared with 5% of the treatment group.
One in 10 participants in the active group had to be treated with rescue epinephrine during the exit food challenge, compared with 53% of participants in the placebo group, and the number who required a second dose of rescue epinephrine was 1% and 15%, respectively.
“These data show that, in the context of a clinical trial, among participants 4-17 years of age, AR101 had immunomodulatory activity, raised the threshold dose of peanut exposure triggering the onset of clinically significant allergic symptoms (among participants having symptoms), during the double-blind, placebo-controlled exit food challenge, and attenuated the severity of those symptoms when they occurred,” wrote Brian P. Vickery, MD, of Emory University in Atlanta, and his coauthors.
The 55 participants aged 18-55 years were analyzed separately, and researchers found that for the 600 mg exit food test, the difference between the two groups did not reach statistical significance.
Apart from adverse events that occurred during the exit food challenge, the rate of adverse events was slightly higher in the treatment group compared to the placebo group (98.7% vs. 95.2%). The most common adverse events in the treatment arm were abdominal pain, vomiting, oral pruritis, and nausea.
The study was funded by Aimmune Therapeutics. Three authors were employees of or investigators for Aimmune Therapeutics and one also had a patent pending for oral immunotherapy for peanut allergy. Most authors declared funding, grants, consultancies, or other support from the pharmaceutical industry, including from some from Aimmune.
SOURCE: Vickery BP et al. N Engl J Med. 18 Nov 2018. doi: 10.1056/NEJMoa1812856.