Aimmune Therapeutics, Inc. (Nasdaq:AIMT), a biopharmaceutical company developing treatments for potentially life-threatening food allergies, today announced the online publication of positive data from its ARC001 Phase 2 clinical trial of AR101 in The Journal of Allergy and Clinical Immunology: In Practice.1 AR101, Aimmune's investigational biologic oral immunotherapy (OIT) for desensitization of patients with peanut allergy, is currently in Phase 3 clinical trials, with pivotal data expected in the first quarter of 2018.
The ARC001 study enrolled 55 peanut-allergic subjects, ages 4–21. The study was the first randomized, placebo-controlled Phase 2 peanut oral immunotherapy study to include double-blind, placebo-controlled food challenges at both entry and exit. The study was also the first conducted using an investigational oral biologic drug with a characterized peanut protein profile, manufactured to cGMP standards and intended for potential commercialization.
The ARC001 study met its primary endpoint, providing evidence that AR101 has immunomodulatory activity, which, after approximately six months of treatment, significantly reduced clinical reactivity in almost 80 percent of the peanut-allergic subjects randomized to AR101 treatment.
"ARC001 was the first Phase 2 peanut OIT study to use sufficiently rigorous design features, providing preliminary but high-quality evidence that AR101 has immunomodulatory activity that can significantly reduce clinical reactivity to peanut in an appropriately supervised clinical setting," said J. Andrew Bird, M.D., Associate Professor at the University of Texas Southwestern Medical Center, and lead author of the publication. "Larger and longer placebo-controlled studies will enable us to better characterize the efficacy and safety of AR101 in even broader populations. I am looking forward to seeing the results from Aimmune's Phase 3 PALISADE trial of AR101."
The primary endpoint of the Phase 2 study was the proportion of subjects in each arm able to tolerate a single highest dose of at least 300 mg of peanut protein, with no or only mild symptoms, at an exit double-blind, placebo-controlled food challenge (DBPCFC). The exit DBPCFC tested consecutive doses of 3, 10, 30, 100, 300, and 600 mg of peanut protein, given 20 to 30 minutes apart, as tolerated with no or mild symptoms.
In the intention-to-treat (ITT) analysis, 23 of 29 AR101 subjects (79 percent) tolerated a single highest dose of at least 300 mg of peanut protein, versus 5 of 26 placebo subjects (19 percent) (p<0.0001). Additionally, 18 of 29 AR101 subjects (62 percent) tolerated a single highest dose of 600 mg of peanut protein, versus 0 of 26 placebo subjects (0 percent) (p<0.0001).
"The ARC001 study demonstrated that approximately six months of AR101 treatment significantly raised the level of tolerance of peanut protein, compared to placebo," said Aimmune CEO Stephen Dilly, M.B.B.S., Ph.D. "The observed differences in response rate between AR101 and placebo groups on the ITT analysis were 60 percent for the 300-mg endpoint (95% CI 34-87%) and 62 percent for the 600-mg endpoint (95% CI 37-87%). The lower bound of the 95% confidence interval on the ARC001 ITT analysis greatly exceeded the minimally clinically meaningful difference of 15 percent agreed to with the FDA for our Phase 3 PALISADE study primary endpoint."
Of the AR101 subjects who completed the desensitization protocol (n=23), all tolerated the 300-mg dose of peanut protein. Further, 78 percent of those subjects tolerated the 600-mg dose of peanut protein, corresponding to cumulative equivalents of approximately one and a half peanuts (443 mg total) and approximately three to four peanuts (1,043 mg total), respectively.
Consistent with the known mechanisms of OIT, transient allergic symptoms occurred in nearly all AR101 subjects, with 96 percent of those symptoms being mild, not dose-limiting, and not requiring medical intervention. No adverse events were graded as severe. Gastrointestinal (GI) symptoms were the most common treatment-related adverse events in both the AR101 and the placebo subjects. Recurrent GI symptoms led to the early withdrawal from treatment of four AR101 subjects and contributed, along with other factors, to the early withdrawal of two additional AR101 subjects. In all six AR101 subjects who withdrew (21 percent), the GI symptoms resolved within three weeks of discontinuing treatment.
"In our studies, we have worked to not only test AR101 as a potential peanut allergy treatment, but also to gain understanding of peanut allergy that could help advance the field," said Daniel Adelman, M.D., Chief Medical Officer of Aimmune. "Patients treated with AR101 were more likely to proceed through the steps of the food challenge without experiencing dose-limiting symptoms compared to placebo. In addition, when reactions did occur at the higher doses, the symptom severity was markedly reduced for patients treated with AR101 compared to placebo."
"We're hopeful that our ongoing studies of AR101 will confirm its potential as a treatment that improves upon the current standard of care, which is limited to diagnosis, avoidance of the allergenic food, and treatment of allergic reactions from accidental ingestion with epinephrine or other appropriate medication," said Dr. Adelman. "We're also grateful for the collaboration of leading food allergy oral immunotherapy investigators, and the commitment of peanut-allergic clinical trial participants and their families, as we work to establish a validated approach to treatment that could change practice and provide a reassuring level of protection to peanut-allergic patients."
About Aimmune Therapeutics
Aimmune Therapeutics, Inc., is a clinical-stage biopharmaceutical company developing treatments for potentially life-threatening food allergies. The company's Characterized Oral Desensitization ImmunoTherapy (CODIT™) approach is intended to achieve meaningful levels of protection by desensitizing patients with defined, precise amounts of key allergens. Aimmune's first investigational biologic product using CODIT™, 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 and is currently being evaluated in Phase 3 clinical trials. For more information, please see www.aimmune.com.
1. JA Bird et al. Efficacy and safety of AR101 in oral
immunotherapy for peanut allergy: results of ARC001, a randomized,
double-blind, placebo-controlled Phase 2 clinical trial. Journal of
Allergy and Clinical Immunology: In Practice.
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 expectations regarding the potential benefits of AR101; Aimmune's expectations for its Phase 3 PALISADE trial of AR101, including the timing of topline data for the trial, which is expected in the first quarter of 2018; and Aimmune's expectations regarding potential applications of the CODIT™ approach to treating life-threatening food allergies. 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 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; Aimmune's dependence on the success of AR101; 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 its Quarterly Report on Form 10-Q for the quarter ended June 30, 2017. 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.