Aimmune Therapeutics Announces Phase 2 Follow-On Study of AR101 for the Treatment of Peanut Allergy Demonstrated Increased Desensitization and Improved Tolerability with Low-Dose Maintenance
— All Patients Who Completed 12 Weeks of Low-Dose Maintenance Therapy in the ARC002 Trial Were Desensitized to Levels of Peanut Protein Far Exceeding Those of Typical Accidental Exposures —
— Dr. J. Andrew Bird Presented Data Confirming Safety and
Demonstrating Efficacy of AR101 for the Treatment of Peanut Allergy at
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.
“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
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
“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
AR101 Biomarker Data
Antibodies measured in ARC001 and ARC002 at baseline and post–up-dosing also showed that treatment with AR101 was associated with significantly increased peanut-specific IgG4 antibodies, and a significantly decreased ratio of peanut-specific IgE to IgG4. In oral desensitization immunotherapy, the graded exposure to allergen leads to the production of IgG4 antibodies, which may compete with and inhibit the actions of IgE antibodies. IgG4 antibodies elicited during immunotherapy, therefore, are thought to play a role in dampening the symptoms of allergic reactions over time.
The median peanut skin prick test wheal size significantly declined from baseline to post–up-dosing in both ARC001 and ARC002, from 14 to 6.5 mm and from 12 to 7 mm, respectively.
About Food Allergies
Food allergies are a significant and growing health problem in
About AR101 and CODIT™
AR101 is part of Aimmune’s approach to treating food allergies using its CODIT™ (characterized oral desensitization immunotherapy) system. The CODIT system leverages extensive independent scientific research on oral immunotherapy demonstrating that food allergy patients can be desensitized to food allergens by being administered well-defined, gradually increasing doses of the allergen over a period of months. Aimmune’s CODIT system is designed to precisely control the amounts of the allergens administered in a systematic dosing regimen, beginning with very low doses of the allergens. Once a patient attains a clinically meaningful level of desensitization, the patient continues to take a daily maintenance dose of the CODIT system product in order to maintain the desensitization.
Statements contained in this press release regarding matters that are
not historical facts are “forward-looking statements” within the meaning
of the Private Securities Litigation Reform Act of 1995. Because such
statements are subject to risks and uncertainties, actual results may
differ materially from those expressed or implied by such
forward-looking statements. Such statements include, but are not limited
to, statements regarding: Aimmune’s development efforts, including the
size and timing of the planned Phase 3 PALISADE trial; Aimmune’s
expectations regarding the potential benefits of AR101; Aimmune’s
commercialization plans; and Aimmune’s expectations regarding potential
applications of its CODIT™ system. Risks and uncertainties that
contribute to the uncertain nature of the forward-looking statements
include: the expectation that Aimmune will need additional funds to
finance its operations, the potential for unanticipated capital needs;
the company’s ability to initiate and/or complete clinical trials; the
unpredictability of the regulatory process; the possibility that
Aimmune’s clinical trials will not be successful; the company’s reliance
on third parties for the manufacture of the company’s product
candidates; possible regulatory developments in
This press release concerns a product that is under clinical
investigation and that has not yet been approved for marketing by the