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

Aimmune Therapeutics, Inc. (Nasdaq:AIMT), a biopharmaceutical company developing CODIT™(characterized oral desensitization immunotherapy) treatments for life-threatening food allergies, today announced data from the open-label ARC002 Phase 2 trial of its lead product candidate, AR101 for the treatment of peanut allergy. 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.

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 the United States, Europe and throughout the developed world. It is estimated that more than 30 million people in the United States and Europe have a food allergy, and more than five million people in the United States and Europe have peanut allergy, including more than two million children. The prevalence of peanut allergy in children in the United States is estimated to have increased at a constant annual growth rate of approximately 10 percent between 1997 and 2008, and experts believe it has continued to rise since 2008. For people living with food allergies, certain foods can cause severe allergic reactions, including potentially life-threatening anaphylaxis. There are no approved medical therapies to cure food allergies or prevent their effects. Currently, food-allergic patients manage their condition by strict allergen avoidance and carrying epinephrine auto-injectors for use in case of accidental exposure. Thus, in addition to the unmet medical need, food allergies can impose a significant quality of life burden. For more information, please see www.foodallergy.org and www.niaid.nih.gov/topics/foodallergy.

About AR101 and CODIT™

Aimmune Therapeutics is developing AR101 as a potential desensitization therapy for patients with peanut allergy to provide them with protection from peanut allergens at a level believed to substantially exceed the amount typically encountered in an accidental exposure. AR101 maintains the complete range of natural peanut proteins, which are rigorously analyzed and combined with pharmaceutical-grade ingredients to ensure that each dose has consistent amounts of peanut protein with well-defined concentrations of peanut allergens, especially the three key allergenic proteins (Ara h1, h2 and h6). Patients ingest AR101 mixed into small amounts of palatable, age-appropriate food.

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.

About Aimmune Therapeutics

Aimmune Therapeutics, Inc., is a clinical-stage biopharmaceutical company developing treatments for life-threatening food allergies. The company’s CODIT™ (characterized oral desensitization immunotherapy) system uses rigorously characterized product candidates with gradual, controlled up-dosing protocols to obtain clinically meaningful desensitization to food allergens. Aimmune’s first CODIT product, AR101 for the treatment of peanut allergy, has received the FDA’s Breakthrough Therapy Designation for the desensitization of peanut-allergic patients 4-17 years of age. Aimmune’s Phase 3 trial of AR101, PALISADE, is now enrolling patients. For more information, please see www.aimmune.com.

Forward-Looking Statements

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 the United States and foreign countries; and the company’s ability to attract and retain senior management personnel. These and other risks and uncertainties are described more fully in Aimmune’s most recent filings with the Securities and Exchange Commission, including the Annual Report on Form 10-K for 2015 filed on March 3, 2016. All forward-looking statements contained in this press release speak only as of the date on which they were made. Aimmune undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

This press release concerns a product that is under clinical investigation and that has not yet been approved for marketing by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). It is currently limited to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated.

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