On the heels of positive data from its PALISADE pivotal trial, Aimmune Therapeutics (NASDAQ:AIMT) plans to submit a biologics license application with the FDA by the end of 2018 for its peanut allergy therapy, AR101.
“We set the efficacy bar high in our clinical testing with the goal of achieving meaningful levels of allergy protection,” CFO, Eric Bjerkholt, says in an interview with BioTuesdays. “We hope to receive FDA approval by the third quarter of 2019 and launch by the end of 2019.”
That approval could be the first for any food allergy treatment, an accomplishment that would be shared with food allergy advocates, who helped establish the company earlier this decade to pursue a promising approach studied in academic research.
Mr. Bjerkholt explains that research suggests that patients with food allergies can be desensitized to exposure to food allergens by ingesting controlled, increasing amounts of the allergen over a period of time, an approach known as oral immunotherapy (OIT).
Building on OIT research, Aimmune’s CODIT platform, or Characterized Oral Desensitization ImmunoTherapy, has been designed as a standardized approach using characterized pharmaceutical products to treat food allergies, starting with peanut allergy, where gradually increasing doses of AR101 would desensitize patients to peanut over a period of about six months. Afterward, patients would continue to take maintenance doses of AR101, as the level of desensitization will continue to improve with time.
AR101 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.
“CODIT is very much a platform technology that can be applied to other allergies, with a six-month up-dosing phase followed by ongoing maintenance,” Mr. Bjerkholt points out.
The company is developing two other biologics for egg and walnut allergies, with plans to begin Phase 2 testing in 2019. “Our goal is file an IND for the egg therapeutic, AR201, by the end of 2018 and for a walnut IND for AR301 approximately six months later,” he adds.
In February, Aimmune reported that its PALISADE Phase 3 study met the primary efficacy endpoint, as 67.2% of AR101 patients aged four-to17 tolerated at least a 600-mg dose of peanut protein in the exit food challenge, compared with 4% of placebo patients. The 600-mg dose has the protein equivalent of approximately two peanut kernels. Before treatment, patients had been able to tolerate, at maximum, the equivalent of approximately one tenth of a single peanut kernel.
The trial enrolled 498 peanut-allergic patients aged four-to-17 at more than 60 clinical sites in North America and eight countries in the EU.
In addition, the lower bound of the 95% confidence interval of the difference between treatment arms at the primary endpoint was 53%, greatly exceeding the pre-specified threshold of 15%.
PALISADE Met Primary and Key Secondary Efficacy Endpoints for Ages 4-17.
Compared with placebo, in the exit food challenge, the AR101 treatment group developed fewer moderate and severe symptoms; required more peanut exposure for the onset of symptoms; was more likely to complete the challenge; and needed less epinephrine.
In the U.S., AR101 has FDA fast track designation and FDA breakthrough therapy designation for peanut-allergic patients aged four-to-17.
Mr. Bjerkholt also points out that Aimmune has three active late-stage AR101 studies underway. They include an open-label follow-on trial to PALISADE, ARC004, crossing PALISADE placebo patients over to active treatment and rolling AR101 patients over to extended maintenance. Aimmune plans a data cut from this trial in the third quarter of 2018.
Aimmune also expects data from the RAMSES trial, taking place in the U.S. and Canada and designed to illuminate real-world patient and allergist experiences with AR101, in the second half of 2018, followed by data from the ARTEMIS trial, a dedicated European study of AR101, in early 2019.
The company plans to file a marketing authorization application with the European Medicines Agency in the first half of 2019.
According to Mr. Bjerkholt, the prevalence of peanut allergy is some six million individuals in the U.S. and Europe, of which about half are in the four-to-17 age group, almost equally divided between the U.S. and Europe. “We have first mover advantage in this potentially life-threatening indication and our goal is to build a trusted brand.”
He says Aimmune’s Florida manufacturing plant has the commercial capacity to meet global demand and also produce enough AR101 to treat about 200,000 new patients a year.
There are about 5,000 allergists in the U.S. A survey by the American Academy of Allergy, Asthma and Immunology in 2015 found that 75% of allergists would prescribe an FDA-approved oral immunotherapy, with the remainder needing more information. “For kids and teens, we think this is a good solution,” Mr. Bjerkholt suggests.
He also points out that AR101 in-office dosing would be similar to allergy shots. And payer market research suggests strong access for this life-threatening pediatric indication, he adds.
Aimmune plans to build a sales force to promote AR101 to allergy group practices. “We think we can accomplish our sales and marketing objectives with a team of 80-to-100 sales people,” Mr. Bjerkholt figures. The company plans to hire a VP of sales this year and build out the sales team closer to launch.
“The therapeutic goals of AR101 align with what parents want, specifically a meaningful level of protection for their kids against an accidental exposure to peanut, with no or muted reactions,” Mr. Bjerkholt contends. “Parents want to know that if their kids go through the therapy, they are protected.”
As part of its goal on advancing the field of food allergies, Aimmune has collaborations with Golden Peanut and Tree Nuts, Nestlé Health Science, and Regeneron and its strategic alliance collaborator, Sanofi.
Nestlé Health Science has injected $175-million into Aimmune for a 15% stake under a two-year collaboration that ends in November 2018. The accord is focused on expansion of Aimmune’s pipeline and Aimmune retains full commercial rights to all CODIT pipeline assets, including AR101.
Mr. Bjerkholt says the innovation accord with Regeneron involves Phase 2 testing, sponsored by Regeneron, of AR101 with adjunctive use of dupilumab in 2018. “The plan is to explore sustained unresponsiveness in peanut allergy or a potential functional cure,” he adds.
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