Global enrollment is complete in the first of two pivotal trials that will back 2018 regulatory filings for the experimental oral peanut allergy treatment AR101, developed by Aimmune Therapeutics Inc. Top-line data from PALISADE, the first phase III study, is expected in the fourth quarter of 2017. News of the milestone was accompanied by word that Nestlé Health Science's $145 million equity investment in the company has closed.
In addition, Aimmune on Monday announced a third phase III trial in the works, "AR101 Trial in Europe Measuring oral Immunotherapy Success," or ARTEMIS, which has been organized to develop data expected to help support Aimmune's European labeling ambitions and to help its cause with European health technology assessment authorities. The company plans to initiate ARTEMIS in mid-2017, Aimmune's chief medical officer Daniel Adelman told BioWorld Today.
PALISADE, a "Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults," will randomize about 540 people with peanut allergy in a 3:1 ratio to either a dose of AR101 that will ascend to 300 mg or to placebo. The double-blind study, which will include patients ages 4 to 55, will measure the proportion of subjects who can tolerate at least 1,043 mg of cumulative of peanut protein after six months of maintenance treatment with 300 mg of AR101 – representing about three to four peanuts, depending on size. It will also measure the percentage of those who can tolerate 2,043 mg with no more than mild symptoms during a double-blind placebo-controlled food challenge, though that's not its primary endpoint. (See BioWorld Today, March 16, 2015.)
PALISADE will be followed by Aimmune's second pivotal trial, "Real-World AR101 Market-Supporting Experience Study," which is expected to start in the first quarter of 2017. Dubbed RAMSES, the double-blind study will randomize participants 2:1 to AR101 or placebo, but will not require an oral food challenge for entry as in PALISADE. Instead, patients will be selected based on criteria including a medical history of IgE-mediated reactions to peanuts including anaphylaxis, skin reactivity, and analyses of peanut-specific immunological markers. It will monitor treatment-emergent adverse events during the initial six-month dosing period and thereafter. The company expects that the absence of an entry food challenge may further improve the tolerability profile of AR101 in early stages of dosing by removing exposure to high levels of peanut allergen that may otherwise prime the immune system prior to treatment.
ARTEMIS, the European study, will look much like PALISADE but with a few key differences, Adelman said. First, it's a European-only study, responding to heavy demand for participation in testing of AR101 that couldn't be met with PALISADE. It also focuses on children and adolescents, rather than including adults, too.
"What we're particularly interested in doing is looking at the proportion of patients who can tolerate 2,043 mg [of peanut protein] after up-dosing and three months of maintenance," said Adelman, expressing his hope that the trial would help Aimmune "understand the kinetics of protection" after just three months of maintenance therapy. "We want to be able to demonstrate that there is protection against a larger amount of peanut protein so that we can get a label that allows us to make the claim of protection," he said.
PALISADE and RAMSES will form the basis of the Brisbane, Calif.-based company's BLA filing with the FDA. Together with ARTEMIS, they'll be used to back Aimmune's European marketing authorization application for AR101.
The company also expects to follow patients taking AR101 to get a better sense of its long-term efficacy in sensitizing patients.
Should Aimmune win over the FDA and EMA, its next challenge will be to persuade clinicians, patients, caregivers and payers that AR101 has therapeutic value not as a cure for peanut allergy, but simply as a means of obtaining protection from accidental exposure to peanut protein. Clinical evidence that it can cover larger accidental exposures as well the lack of any cure for already-allergic individuals should help.
Backing from Nestlé, the world's largest food company, will no doubt help too. The $145 million equity investment will "enable us to be able to pursue not only our lead program, but also our pipeline a little more aggressively," said Adelman.
Shares in Aimmune (NASDAQ:AIMT), which Nestlé bought for $19.20 each, traded for $24.53 each at Monday's market close, down 1.5 percent.