Aimmune Lays Foundations In Europe For Lead Peanut Allergy Therapeutic
Executive Summary
With Aimmune’s AR101 oral immunotherapeutic nearing the market in the EU and US, the company sketches out its European business strategy after ARTEMIS meets its primary endpoint.
Brisbane, California-based Aimmune Therapeutics Inc. already has the “foundations of a European commercial organization,” with an office in the UK and a legal entity in the Netherlands, president and CEO Jayson Dallas reported on March 25, 2019, as the company presented top-line data from the Phase III ARTEMIS study showing its candidate peanut allergy therapeutic, AR101, met its primary endpoint in the European trial.
The ARTEMIS study is the second Phase III study, after the company’s PALISADE study, to show AR101 has a statistically significant beneficial effect on how much peanut protein allergic patients can tolerate. AR101 is an oral immunotherapy which involves taking capsules containing a gradually increasing dose of peanut protein daily for six months, with maintenance doses taken thereafter to maintain desensitization (see sidebar).
The results place Aimmune in a leading position in the race to develop an effective therapy for peanut allergy; it has already submitted the AR101 BLA for US approval, in December 2018, with the outcome expected in late January 2020, while a European marketing submission is expected in mid-2019, with Germany as the rapporteur country, and approval around 12 months after that.
Among other companies developing peanut allergy therapies, France’s DBV Technologies SA said it was expecting to resubmit a US BLA for its Viaskin Peanut patch in the third quarter of 2019. And UK-headquartered Allergy Therapeutics PLC is planning to start clinical studies with a peanut allergy product this year. (Also see "Allergy Therapeutics Progresses Grass And Peanut Allergy Vaccines, Plans For US Entry" - Scrip, 6 Mar, 2019.)
A Cornerstone Therapy
“AR101, if approved, will become the cornerstone of care for patients with peanut allergy,” Dallas remarked during an analysts’ briefing on the same day the ARTEMIS results were released. The analysts tended to agree, with some reckoning that AR101 could achieve annual sales of over a billion dollars starting in 2023. Others cautioned the commercial opportunity could be affected by the need for frequent visits to physicians during AR101 therapy, and the product’s potential to be associated with gastro-intestinal side effects.
Around six million people are allergic to peanuts in the US and Europe, around half of them aged between four and 17 years, Dallas told the briefing. Peanuts are everywhere, and allergic reactions to the nuts have the potential to be fatal, he noted. The aim of AR101’s development is to protect sufferers from the effects of accidental exposure.
Aimmune Therapeutics is now the only company to complete two successful Phase III efficacy trials in peanut allergy, Dallas reported. The company has around $340m in cash, sufficient funds to commercialize AR101 in both the US and Europe, and also to advance its pipeline of anti-allergy products, including a candidate milk allergy product.
European approval of AR101 is expected in mid-2020, with launch in Germany straight after and the submission of reimbursement dossiers in other key EU markets, with launches in the remaining countries between 12 and 18 months after the German launch, Dallas said. “We’re well into our market research in the different countries,” he noted, pointing out that “we are looking to hire somebody to lead the marketing effort in Germany.” Some countries, like France, already embrace oral immunotherapy (desensitization) across all different kinds of food allergies, while in other European countries, oral immunotherapy is not part of medical practice.
In the US, Aimmune laid out potential US commercialization plans when it announced top-line results from the PALISADE study, in February 2018. It expects a field team of around 80-120 reps could target around 5,000 allergists in the US.
Commercializing an allergy immunotherapy is likely to be different to a traditional pharmaceutical, and Aimmune says it is not actively looking for an EU partner, at least initially. That's partly because, with regard to the commercial model, “we want to make certain that we get it right in the core markets in Europe,” Dallas said. However, “the door remains open” if somebody comes to us with a partnering offer, he added.
Top-Line Data
In the ARTEMIS study, subjects were able to tolerate an amount of peanut protein equivalent to three of four peanut kernels, and “this level of protection provides ample buffer beyond a typical bite of a peanut-containing food in the real world,” Dallas said.
The proportion of AR101-treated patients who tolerated a 1,000 mg dose of peanut protein (a 2,043 mg cumulative dose) in a blinded exit challenge after approximately nine months of AR101 treatment was significantly higher (p < 0.00001) than in the placebo group.
The median tolerated dose of peanut protein for AR101-treated patients improved 100-fold, from 10 mg at baseline to 1,000 mg at exit. The trial greatly exceeded a 15% lower-bound of the 95% confidence interval (CI) of the difference between treatment arms for all endpoints.
There were no cases of anaphylaxis or eosinophilic esophagitis. The clinical trial enrolled 175 children and adolescents aged from 4 to 17 years at sites in France, Germany, Ireland, Italy, Spain, Sweden and the UK. Patients underwent six months of dose escalation and three months of 300 mg of AR101, or placebo, followed by an exit double-blind placebo-controlled food challenge.
Aimmune did not release further details, including the proportion of patients that had achieved protection, saying that the full results would be presented at an oral presentation at the June congress of the European Academy of Allergy and Clinical Immunology (EAACI), to take place in Lisbon, Portugal.
Other Studies
In December 2018, Aimmune started the Phase III POSEIDON trial, aimed at desensitizing one- to three-year-old infants with peanut allergies. The primary efficacy endpoint in the study is tolerating a 600 mg single dose of peanut protein with no more than mild symptoms after approximately one year of treatment. Peanut allergies are often diagnosed in the first or second year of life.
Aimmune is also collaborating with Sanofi and Regeneron Pharmaceuticals Inc. on a Phase II study combining AR101 with the two companies’ anti-allergic, dupilumab (Dupixent), for the potential use of the combination in peanut allergy. Dupilumab targets the IL-4/IL-13 signalling pathway, which is believed to drive allergic inflammation.
Aimmune has previously attracted Nestle Health Science SA, the health sciences arm of the food products giant, Nestle, as an investor, with the entity increasing its stake in Aimmune to 19% in November 2018. (Also see "Finance Watch: Not Everyone Can Go Public, But Biopharma IPOs Are Using Multiple Markets" - Scrip, 15 Nov, 2018.)