Update on Immunotherapies for Peanut Allergy
Two immunotherapy treatments for peanut allergy have completed Phase 3 clinical trials and are nearing submission for regulatory approval. If one or both of these therapies are approved by the Food and Drug Administration (FDA), standardized peanut allergy immunotherapy could become available as soon as next year.
On Feb. 20, Aimmune Therapeutics announced results from the PALISADE clinical trial to test the efficacy of AR101, a characterized peanut product for oral immunotherapy. AR101 met its primary endpoint for the trial, demonstrating a very significant difference between response to active treatment and response to placebo.
PALISADE enrolled 499 patients ages 4 to 17. Patients were highly allergic to peanut at the outset of the trial, being unable to tolerate a 30-mg dose of peanut protein. Most of the patients had experienced anaphylaxis, and more than half had a history of asthma. Following a year of treatment, 67 percent of the children who started treatment with AR101 could tolerate eating 600 mg of peanut protein or more, compared to 4 percent of children who received a peanut-free placebo. Among the children who completed the trial, 85 percent of the AR101 group and 4 percent of the placebo group passed the oral food challenge of 600 mg peanut protein (approximately two peanuts).
Twenty percent of children who began in the AR101 group did not complete the trial; 13 percent left because of adverse reactions reported by investigators, including gut symptoms and systemic allergic reaction. Seven children discontinued following anaphylaxis, which in one instance was severe. One child who left the trial following gastrointestinal symptoms was found to have eosinophilic esophagitis. In the placebo group, 7 percent left the trial early, including 2 percent with investigator-reported adverse reactions.
An additional 55 adult patients (ages 18 to 49) enrolled in PALISADE. Among the AR101 treatment group of 41 adults, more than half left the study. Twenty percent of the treated group left in response to adverse reactions. Of those who completed the trial, 85 percent of the adults who received AR101 passed the 600-mg exit challenge, compared to 15 percent of adults who received placebo.
With positive Phase 3 results in hand, Aimmune’s next steps will likely be the submission to FDA of a Biologics License Application (BLA), a request for permission to bring a biologic drug to market. Also nearing FDA submission is DBV Technologies’ Viaskin Peanut (epicutaneous immunotherapy for peanut allergy, also known as the “peanut patch”). On Feb. 14, DBV Technologies reported FDA’s agreement that Viaskin Peanut efficacy and safety data supports the submission of a BLA to market the patch as a treatment for peanut allergy in children ages 4 to 11.
Three months before Aimmune announced the results of the PALISADE trial, DBV released results from the PEPITES trial, which evaluated the efficacy and safety of Viaskin Peanut 250 µg in 356 children. Viaskin Peanut did not meet its primary endpoint for efficacy in the trial. Thirty-five percent of the treatment group and 14 percent of the placebo group responded during the course of the trial. The high rate of response to placebo meant that the difference in response rates between treatment and placebo groups was lower than the minimum required to meet the endpoint.
At the same time, an October 2017 DBV press release reported that Viaskin Peanut treatment resulted in a statistically significant response. At the start of the PEPITES trial, the cumulative reactive dose (CRD, the total amount consumed in an oral food challenge before a reaction occurred) averaged 210 mg of peanut protein for both the treatment and placebo groups. After one year, the average CRD for children who received Viaskin Peanut was 900 mg, compared to a CRD of 360 mg for the placebo group.
The PEPITES trial showed that Viaskin Peanut was well-tolerated. The dropout rate of 10 percent was evenly balanced between the treatment and placebo groups. No instances of anaphylaxis were reported. The most common adverse effects involved localized reactions at the site where the patch was applied. On average, patient compliance exceeded 95 percent.
Stay tuned for more news as these immunotherapy approaches to peanut allergy treatment advance toward commercial release.