Aimmune Therapeutics, Inc. (Nasdaq:AIMT), a biopharmaceutical company developing treatments for potentially life-threatening food allergies, reported additional results from its pivotal Phase 3 PALISADE trial of AR101 for the treatment of peanut allergy at the Congress of the European Academy of Allergy, Asthma, and Immunology (EAACI) 2018 in Munich. Aimmune previously announced that the trial met its primary and secondary efficacy endpoints in the pre-specified primary analysis of the 4-17 age cohort (see March 4 press release). Additional analyses including adults treated in the study were presented at EAACI.
PALISADE enrolled a total of 554 patients ages 4-55 (90% ages 4-17). After approximately one year of treatment (up-dosing and maintenance), clinical reactivity to peanut protein was assessed in an exit double-blind, placebo-controlled food challenge (DBPCFC). The trial met its primary endpoint as 67% of AR101 patients ages 4–17 tolerated at least a 600-mg dose of peanut protein in the exit DBPCFC, compared to 4% of placebo patients (p<0.00001). The lower-bound of the 95% confidence interval (CI) of the difference between treatment arms at the primary endpoint was 53%, greatly exceeding the pre-specified threshold of 15% (p<0.00001).
Based on these results, Aimmune plans to submit a Biologics License Application (BLA) for AR101 to the U.S. Food and Drug Administration (FDA) by the end of 2018, followed by a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) in the first half of 2019. In the United States, AR101 has FDA Fast Track Designation, as well as FDA Breakthrough Therapy Designation for peanut-allergic patients ages 4–17.
Efficacy Across All Age Groups
New analyses presented at EAACI of the 4-55 age intent-to-treat population showed a statistically significant difference of 60% between the proportion of patients in the AR101 group (65%) and placebo group (5%) who tolerated the 600-mg dose of peanut protein in the exit DBPCFC (p<0.00001; 95% CI: 50, 69). In an exploratory analysis of AR101 patients who completed the trial, efficacy was similar across all ages, refined into three groups. In the exit DBPCFC, 85% of children (ages 4-11), 83% of adolescents (ages 12-17), and 85% of adults (ages 18-55) tolerated the 600-mg dose of peanut protein. Though the number of adults in the study was small, the treatment difference in this population showed a strong trend on an intent-to-treat basis (p=0.07). The safety profile in adults was similar to that observed in the pediatric and adolescent populations previously reported.
“There is a significant need for approved treatments for peanut allergy as it can be profoundly disruptive to the lives of families caring for affected loved-ones and costly to them and the healthcare system,” said Prof. George du Toit, M.B., B.Ch., of King’s College London, Guy’s and St. Thomas’ NHS Foundation Trust, and principal investigator for PALISADE in the United Kingdom, who presented the clinical data at EAACI. “The efficacy and safety profile of AR101 observed in PALISADE are promising and consistent with what I believe would be a valuable solution for many of my patients with peanut allergy should AR101 ultimately be approved. Independent studies have shown that inadvertent exposures to peanut are frequently far beyond trace levels2, so it is exciting to see that AR101 patients of all ages were able to reach desensitization levels that allow ample buffers to those inevitable accidents.”
Biomarkers Show Immunologic Changes Associated with AR101
In a separate late-breaking presentation, Prof. Kirsten Beyer, of University Hospital Charité, Berlin, and principal investigator for PALISADE in Germany, presented new immunological findings from the trial3. Exposure to AR101 was strongly associated with immunologic changes consistent with the immunotherapeutic efficacy, specifically increased peanut-specific IgG4 and decreased peanut skin-prick test wheal size.
New data from the laboratory of Dr. Erik Wambre of the Benaroya Research Institute from a small subset of patients from PALISADE showed that treatment with AR101 was linked to a statistically significant decrease in peanut-specific TH2A cells compared to patients treated with placebo after up-dosing and at the end of the trial2. These findings and similar results from Aimmune’s ARC001 Phase 2 trial suggest that the clinical responses observed with AR101 treatment are associated with fundamental modulation of T cell subsets that drive the allergic response3,4.
“We are deeply grateful to the PALISADE patients, families, and investigators for their contributions to this landmark study in peanut allergy, which brings us a big step closer to delivering on our commitment to the food allergy community of winning approval for our characterized, biologic oral immunotherapy medicines,” said Sue Barrowcliffe, Aimmune’s General Manager in Europe. “We are looking forward to advancing AR101 for the treatment of peanut allergy and additional CODIT™ medicines for treating other important food allergies.”
PALISADE (Peanut ALlergy oral Immunotherapy Study of AR101 for DEsensitization in children and adults) was an international, randomized 3:1, double-blind, placebo-controlled, Phase 3 trial of the efficacy and safety of AR101 in a Characterized Oral Desensitization ImmunoTherapy (CODIT™) approach in patients with peanut allergy.
AR101 is a novel, investigational oral biologic drug for use in oral immunotherapy (OIT) in patients with peanut allergy. The drug, which is manufactured in accordance with current Good Manufacturing Practices (cGMP), has a characterized protein profile found in peanuts, analyzed to ensure consistent major allergen content. The amount of active ingredient in each AR101 capsule is controlled to ensure minimal variability of allergen content across doses of a given strength.
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.
- du Toit, G. et al. Efficacy and Safety of AR101 in Peanut Allergic Patients Aged 4–55: Results from an International Phase 3, Randomised, Double-Blind, Placebo-Controlled Trial (PALISADE). EAACI 2018 (Abstract #1874).
- Deschildres, A. et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists’ dietary advice and lessons from real life. Clinical & Experimental Allergy 2016; 46:610-620.
- Beyer, K. et al. Immune Responses in 496 Patients Aged 4–17 Years with Peanut Allergy Treated with Oral Immunotherapy Using AR101: Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial (PALISADE). EAACI 2018 (Abstract #1672).
- Wambre, E. et al. A phenotypically and functionally distinct human TH2 cell subpopulation is associated with allergic disorders. Sci Transl Med 2017; Aug 2;9(401). pii: eaam9171.
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 regarding potential applications of the CODIT™ approach to treating life-threatening food allergies; Aimmune’s expectations regarding the approvability of AR101; and Aimmune’s expectations regarding the timing of potential regulatory filings for marketing approval of AR101 in the United States and Europe. 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 the results of early clinical trials may not be predictive of future results; 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 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 its Quarterly Report on Form 10-Q for the quarter ended March 31, 2018. 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.