Aimmune Therapeutics, Inc. (AIMT), a biopharmaceutical company developing CODIT™ (Characterized Oral Desensitization ImmunoTherapy) treatments for life-threatening food allergies, today announced that new Phase 2 extended maintenance therapy data from Aimmune’s lead product, AR101 for peanut allergy, showed that the safety and tolerability profile improved with continued treatment, particularly in a low-dose extended maintenance regimen.
Patients on the low-dose extended maintenance regimen of 300 mg of AR101 per day experienced few adverse events, which were primarily mild, and no patients discontinued therapy. The results support the CODIT maintenance regimen in the ongoing Phase 3 PALISADE trial of AR101, which is enrolling peanut-allergic patients 4-55 years of age.
Rima A. Rachid, M.D., Assistant Professor of Pediatrics, Harvard Medical School and Boston Children’s Hospital, Division of Allergy and Immunology, discussed the data today in Vienna at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2016 in a late-breaking oral abstract presentation titled “The safety and tolerability of AR101, an oral immunotherapy (OIT) pharmaceutical formulation for peanut allergy, after more than one year of treatment: Results from an ongoing Phase 2b clinical trial (ARC002), including low-dose (300 mg/day) and high-dose (2,000 mg/day) regimens” (abstract #2362).
“We now have data for treatment with AR101 for at least a year in all patients and almost two years in some. We are seeing not only that most side effects associated with AR101 are typically mild, manageable gastrointestinal adverse events that happen early in up-dosing, but also that the rate of related adverse events decreases substantially during extended maintenance, particularly with low-dose maintenance,” said Dr. Rachid. “From a clinical perspective, it is useful to consider these longer-term safety and tolerability data, along with the strong efficacy data for AR101 previously reported after up-dosing and after 12 weeks of low-dose maintenance therapy, to make treatment decisions. The predictability of knowing that related adverse events occur primarily early in up-dosing would be an important factor for patient management if this is confirmed in larger and longer studies.”
The data are from ongoing study of maintenance dosing in patients who participated in Aimmune’s Phase 2 clinical trials of AR101. After patients completed the initial portion of the Phase 2 trial — the up-dosing regimen, followed by twelve weeks of low-dose, CODIT maintenance therapy at a daily dose of 300 mg of AR101, and then the subsequent double-blind, placebo-controlled food challenge (DBPCFC) — they were offered the options of staying on low-dose (CODIT) maintenance of 300 mg of AR101 per day or attempting up-dosing to a high-dose maintenance target of 2,000 mg of AR101 per day.
All of the 40 patients who completed the initial portion of the Phase 2 trial volunteered to continue on extended maintenance therapy with AR101. Of these, 11 elected to remain on CODIT maintenance therapy of 300 mg of AR101 per day, and 29 chose to attempt up-dosing to high-dose maintenance therapy. The exposure-adjusted, treatment-related, adverse event rate during extended maintenance for patients on CODIT maintenance therapy was one every 574 days. The exposure-adjusted, treatment-related, adverse event rate during extended maintenance for patients on high-dose maintenance therapy was one every 107 days.
The 11 patients who elected to remain on CODIT 300 mg maintenance therapy all remained in the study, and the few adverse events they experienced were almost exclusively mild, with only one categorized as moderate. No patients developed new-onset persistent gastrointestinal symptoms and there were no treatment-related serious adverse events (SAEs) during extended maintenance.
“Our most important objective is the safety of our patients. Our Phase 2 trials have shown that treatment with AR101 can reduce the risk of severe allergic reactions to peanut and that tolerability improves over time,” said Aimmune CEO Stephen Dilly, M.B.B.S., Ph.D. “Now we are demonstrating that AR101’s safety and tolerability profile with low-dose, extended maintenance therapy — our CODIT regimen — appears to be quite acceptable. These data have also shown an advantage in extended maintenance by minimizing peanut taste breakthrough, which we expect to support compliance in patients who have peanut taste aversion.”
“These results reinforce the Phase 3 PALISADE trial design with the CODIT regimen because, as we hypothesized, low-dose maintenance is demonstrating to be better tolerated and is easier for patients to do than high-dose maintenance,” continued Dr. Dilly. “PALISADE will also give us the opportunity to test the expectation, based on academic studies, that low-dose extended maintenance therapy with AR101 could protect to even higher levels of peanut protein exposure than we saw immediately after up-dosing in ARC001 and after 12 weeks of low-dose maintenance therapy in ARC002.”
An early study of low-dose maintenance (Jones et al, 2009 ) and more recent work (Cronin et al, 2014 , and Vickery et al, 2015 ) have shown that a low, 300 mg daily maintenance dose of peanut protein can achieve a high level of desensitization, as patients in these studies were able to tolerate at least 2,100 mg and as much as 5,000 mg of peanut protein in food challenges administered after a year or more of maintenance therapy.
Dr. Rachid also presented biomarker data from extended maintenance therapy with AR101, which showed favorable changes with both low-dose and high-dose extended maintenance, including diminishing peanut skin-prick test wheal diameters, additional reductions in peanut-specific IgE levels, and continued increases in peanut-specific IgG4 levels.
“We are really excited to learn more from biomarker data in our Phase 3 PALISADE trial that is currently underway, along with other planned studies,” said Dr. Dilly. “We hope to confirm the data demonstrated in the Phase 2 study as well as our belief that it may be useful to look at baseline peanut-specific IgE levels to help patients and physicians know what to expect in terms of improving tolerability, and when adjunctive therapies could potentially help. We are also planning to explore signals that could point to sustained unresponsiveness.”
Conference Call on Monday, June 13, 2016, at 4 p.m. Eastern Time
Aimmune will host a conference call and live audio webcast on Monday, June 13, 2016, at 4:00 p.m. Eastern Time to discuss the extended maintenance data.
The conference call will be accessible via the company’s website at www.aimmune.com on the Events page under Investor Relations. Please connect to the company’s website at least 15 minutes prior to the start of the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, participants may dial (877) 497-1438 (domestic) or (262) 558-6296 (international) and refer to conference ID 27715872.
The archived conference call will be available on Aimmune’s website beginning approximately two hours after the event and will be archived and available for replay for at least 30 days after the event. For a telephone replay, please dial (855) 859-2056 (domestic) or (404) 537-3406 (international) and refer to conference ID 27715872.
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 tripled 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 reactions to 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 Characterized Oral Desensitization ImmunoTherapy, or CODIT™, system. The CODIT system leverages extensive independent scientific research on oral immunotherapy, or OIT, 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’s Phase 2 and Phase 3 Clinical Trials
Of the 55 patients who entered Aimmune’s Phase 2 trials (the randomized, double-blind, placebo-controlled ARC001 trial and the ARC002 rollover/crossover trial), 44 patients completed the approximately six-month up-dosing period to a daily dose of 300 mg of AR101. At the end of that period, 43 of those patients tolerated a cumulative amount of 443 mg of peanut protein in a double-blind, placebo-controlled food challenge (DBPCFC). Additionally, 35 of the patients who completed up-dosing tolerated a cumulative amount of 1,043 mg of peanut protein in the DBPCFC, the highest challenge administered at that point. The patients who tolerated at least 443 mg of peanut protein in the post–up-dosing DBPCFC were eligible to continue on 300 mg of AR101 per day in maintenance therapy. After three months of maintenance, the patients (n=40) underwent another DBPCFC, where 100 percent, 90 percent, and 60 percent of patients tolerated cumulative amounts of peanut protein of 443 mg, 1,043 mg, and 2,043 mg, respectively (corresponding to 73 percent, 65 percent, and 44 percent on an intent-to-treat basis with n=55).
With the CODIT regimen, approximately 90 percent of the treatment-related adverse events in Phase 2 have been mild, predominantly allergic, symptoms, consistent with stimulation of the immune system. There have been no treatment-related severe adverse events. One serious adverse event of moderate, non-life-threatening anaphylaxis occurred in Phase 2 early in the course of up-dosing. Ten patients discontinued from the trial for treatment-related reasons, all due directly or indirectly to gastrointestinal adverse events experienced early in the up-dosing regimen. These events typically occurred within the first few weeks of the treatment, and in all cases the symptoms resolved within three weeks of the cessation of treatment.
The primary endpoint in Aimmune’s currently enrolling Phase 3 PALISADE trial of AR101 is tolerating a cumulative amount of at least 1,043 mg of peanut protein after approximately six months of up-dosing and six months of maintenance therapy at a daily dose of 300 mg of AR101. PALISADE 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 the European Union.
About Aimmune Therapeutics
Aimmune Therapeutics, Inc., is a clinical-stage biopharmaceutical company developing treatments for life-threatening food allergies. The company’s Characterized Oral Desensitization ImmunoTherapy (CODIT™) system, an approach to oral immunotherapy (OIT), 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.
 Clinical efficacy and immune regulation with peanut oral immunotherapy. Jones, Stacie M. et al. Journal of Allergy and Clinical Immunology, Volume 124, Issue 2, 292 – 300.e97
 Low Dose Maintenance Peanut Oral Immunotherapy Can Produce Sustained Unresponsiveness. Cronin, Julia A. et al. Journal of Allergy and Clinical Immunology, Volume 133, Issue 2, AB103
 High Rate of Sustained Unresponsiveness with Early-Intervention Peanut Oral Immunotherapy. Vickery, Brian P. et al. Journal of Allergy and Clinical Immunology, Volume 135, Issue 2, AB155.
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; Aimmune’s expectations regarding the potential benefits of AR101; Aimmune’s ability to use biomarkers to predict prospectively how patients will react to AR101; Aimmune’s expectations regarding potential applications of its CODIT™ system; Aimmune’s expectations on increasing compliance in patients with peanut taste aversion; Aimmune’s expectations that low-dose extended maintenance therapy with AR101 could protect to higher levels of peanut exposure than were observed in ARC002; and Aimmune’s plans to explore signals in AR101 that could point to sustained unresponsiveness. 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; Aimmune’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; Aimmune’s dependence on the success of AR101; Aimmune’s reliance on third parties for the manufacture of its product candidates and the conduct of its Phase 3 clinical trial for AR101; possible regulatory developments in the United States and foreign countries; and Aimmune’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 Quarterly Report on Form 10-Q for the period ended March 31, 2016, filed on May 16, 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.