Peanut Immunotherapy Update: DBV Technologies
At last weekend’s annual scientific meeting of the American Academy of Allergy, Asthma & Immunology, Aimmune Therapeutics and DBV Technologies presented updates on the two immunotherapies for peanut allergy that have progressed farthest in the U.S. Food and Drug Administration’s approval process for bringing new drugs to market. Yesterday, we posted on the FARE Blog some of the data reported by Aimmune. Here, we present findings released by DBV.
DBV Technologies submitted a Biologics License Application to FDA in October 2018 for Viaskin Peanut, a patch containing peanut protein that is used in epicutaneous (“on the skin”) immunotherapy, or EPIT, in children ages 4 to 11. That Biologics License Application was voluntarily withdrawn by DBV in December 2018 following input from FDA that the data on manufacturing procedures and quality controls were insufficient.
Viaskin Peanut research presented at AAAAI 2019 included data from the PEPITES (Peanut EPIT Efficacy and Safety) phase 3 trial, which was published in the Journal of the American Medical Association on the first day of the conference. The JAMA article detailed findings previously reported on the FARE Blog, as well as new information.
The PEPITES study enrolled 356 children ages 4 to 11 who had a diagnosed peanut allergy and reacted to 300 mg peanut protein (about one peanut) or less during a double-blind, placebo-controlled food challenge. Viaskin Peanut patches containing 250 µg peanut protein were applied once daily on the skin, with up-dosing accomplished by leaving the patch on for escalating periods of time, up to 24 hours. Wearing Viaskin Peanut did not require restrictions from physical activity and was not disrupted by illness.
Response to treatment was assessed on the basis of improved tolerance relative to the dose that elicited reaction symptoms during the initial, pre-treatment challenge. Participants with a baseline eliciting dose of 10 mg or less were considered responders if the post-treatment eliciting dose was 300 mg or more; participants with a higher baseline eliciting dose, up to the 300 mg eligibility cut-off, were considered responders if the post-treatment eliciting dose was 1 g or more. About 35 percent of the treatment group and 14 percent of the placebo group responded during the course of the trial. While the proportion of responders differed significantly after one year of EPIT with Viaskin Peanut versus one year of treatment with placebo patches, 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 study’s primary endpoint.
The PEPITES study did meet a secondary endpoint for statistically significant increase in the cumulative reactive dose (CRD) – the total amount of peanut protein consumed in an oral food challenge before a reaction occurred – for treatment versus placebo. Prior to treatment, the median CRD value was 144 mg peanut protein for both the treatment and placebo groups. After one year, the median CRD for children who received Viaskin Peanut had risen to 444 mg, an increase equivalent to roughly one peanut. By contrast, the median CRD for the placebo group did not change over the year of treatment.
Comparing eliciting doses pre- and post-treatment, 63 percent of patients receiving Viaskin Peanut showed increased peanut tolerance after 12 months of treatment, while 7 percent became less peanut-tolerant. For the placebo group, 28 percent tolerated a significantly higher dose after one year, but a larger fraction, 34 percent, became more sensitive to peanut and tolerated a significantly smaller dose after the year-long trial.
Viaskin Peanut was found to be safe and well-tolerated. Adherence to treatment exceeded 98 percent, and 90 percent of participants completed the trial, with active treatment and placebo patients leaving at similar rates. Most participants in both groups experienced mild skin reactions at the patch site, which typically improved as treatment progressed. Five participants in the Viaskin Peanut group had serious skin reactions, but none of these led to permanent treatment discontinuation. Three Viaskin Peanut group participants experienced four moderate anaphylactic reactions that responded to epinephrine. Only 1.7 percent of Viaskin Peanut recipients dropped out as a result of treatment-emergent adverse events, that is, adverse events that occurred only after treatment has started. None of these adverse events or discontinuations involved gastrointestinal symptoms.
PEOPLE, an ongoing, open-label follow-up trial to PEPITES, is evaluating Viaskin Peanut 250 µg for up to 36 months.