Aimmune’s phase 2 follow-on study of AR101 to treat peanut allergy shows increased desensitization

All patients who completed 12 weeks of low-dose maintenance therapy were desensitized to levels of peanut protein beyond the 250-300 mg typically found in one peanut kernel.

Low-Dose Maintenance Therapy with AR101 Increased Desensitization

In ARC002, 40 patients completed 12 weeks of post-up-dosing maintenance therapy at a daily dose of 300 mg of AR101. Those patients were then administered a double-blind, placebo-controlled food challenge (DBPCFC), in which 100 percent, 90 percent, and 60 percent tolerated cumulative amounts of peanut protein of 443 mg, 1,043 mg, and 2,043 mg, respectively (corresponding to 85 percent, 77 percent, and 51 percent on an intent-to-treat basis).

Patients who passed the highest challenge level demonstrated protection against a challenge equivalent to seven or eight peanuts.

J. Andrew Bird, M.D., Assistant Professor at the University of Texas Southwestern Medical Center, discussed the results today at AAAAI in a late-breaking oral abstract presentation titled "The efficacy of AR101, a peanut-derived pharmaceutical for oral immunotherapy (OIT), is maintained and tolerability is increased with low-dose maintenance therapy" (abstract L60).

"These data suggest that treatment with AR101 could provide effective protection against accidental ingestion for the majority of peanut allergic individuals," said Dr. Bird. "Accidental exposures to peanut typically involve ingestion of less than one peanut and often just traces of peanut, and we have shown that the levels of desensitization achieved in the post-therapy food challenges after 12 weeks of low-dose maintenance in ARC002 protect against ingestion of more than one peanut for 85 percent of participants in the study. It is particularly encouraging to see that, over time, this treatment was well-tolerated by the majority of participants, as immunotherapy must be sustained to continue to be effective."

ARC002 Confirmed ARC001 Safety and Efficacy During Up-Dosing with AR101

ARC002 is the open-label follow-on study to Aimmune’s ARC001 Phase 2 trial. In ARC002, all 26 patients who received placebo in ARC001 crossed over to active treatment.

Over a period of approximately 22 weeks, 21 of the 26 patients completed up-dosing to reach a daily dose of 300 mg of AR101, at which point they underwent a DBPCFC. Patients then continued on a dose of 300 mg of AR101 per day for a further 12 weeks of maintenance before undergoing a final DBPCFC. Also, 21 patients who received active treatment in ARC001 entered ARC002 and continued to receive 300 mg of AR101 per day for the additional 12 weeks before the final DBPCFC.

The up-dosing portion of the ARC002 trial (the placebo crossover) confirmed the safety findings from the ARC001 Phase 2 trial, announced in June 2015 at the European Academy of Allergy and Clinical Immunology (EAACI) Congress, where more than 90 percent of treatment-related adverse events were graded as mild. ARC002 also confirmed the positive efficacy findings from ARC001, as in the ARC002 post-up-dosing DBPCFC, 95 percent and 81 percent of placebo-crossover patients (n=21) tolerated cumulative amounts of 443 mg and 1,043 mg of peanut protein, respectively.

There were no treatment-related severe adverse events and no serious adverse events in ARC002. At the post-up-dosing DBPCFC, no patients required epinephrine. Five patients discontinued ARC002 during up-dosing, primarily due to gastrointestinal side effects, which resolved within two weeks in all individuals after cessation of treatment.

Low-Dose Maintenance Improved Tolerability of AR101

The ARC002 results showed increasingly good tolerability of AR101 with continued treatment. As many as a third of patients who began up-dosing in ARC002 (placebo crossovers) experienced an adverse event on the initial dosing day, which consists of up to five gradually escalating doses. During the biweekly up-dosing period, ARC002 patients as a whole (placebo crossovers and active rollovers) experienced on average an adverse event approximately once a month. During daily maintenance therapy, the rate decreased to about once every two to three months.

"Together, our ARC001 and ARC002 trials show that we have made significant progress toward our goal of providing real-world protection to people at risk of dangerous reactions to accidental exposures to peanut," said Aimmune CEO Stephen Dilly, M.B.B.S., Ph.D.

"The meaningful level of protection we saw after just 22 weeks of AR101 treatment could protect against amounts exceeding those associated with cross-contamination, and that efficacy appears even stronger after 12 weeks of maintenance. The improved tolerability AR101 showed in maintenance is a great sign as well.

"Looking at our results in the broader context of work discussed at this AAAAI meeting, we’re especially excited by new data from the LEAP-On, EAT and DEVIL studies that have given us potential pointers to the feasibility and long-term benefits of early and regular oral exposure to allergenic foods in young children, including those in whom clinical allergy has already become apparent. This work helps inform our active planning of our ARC005 pediatric study in children, including ages one to three, which we expect to initiate next year," continued Dr. Dilly.

"At the same time, our Phase 3 PALISADE trial should give us the opportunity to examine all of these Phase 2 responses on a much larger scale. We believe we can make a real impact in helping to alleviate stress and fear and prevent tragedies associated with peanut allergy."

Aimmune’s Phase 3 PALISADE trial of AR101 for treatment of peanut allergy is now enrolling patients at many sites. PALISADE (PEANUT ALLERGY ORAL IMMUNOTHERAPY STUDY OF AR101 FOR DESENSITIZATION IN CHILDREN AND ADULTS) is a randomized 3:1, double-blind, placebo-controlled trial expected to enroll approximately 500 peanut-allergic patients 4-55 years of age at more than 60 clinical sites in the United States, Canada, and nine countries in the European Union.