No surprises in FDA staff review for Aimmune peanut allergy therapy — focus remains on safety, tolerability profile
Ahead of the keenly anticipated independent panel set to discuss Aimmune’s peanut allergy immunotherapy on Friday, FDA staff issued a predictable review on Wednesday, highlighting the potential safety and tolerability issues associated with the product, while backing its efficacy.
Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. In the United States, data suggest peanut allergies affect an estimated 1.2% of the total population — this is the market Aimmune is itching to address with its immunotherapy.
The product — AR101 — is effectively a small amount of encapsulated peanut flour. It is first given in escalating doses to essentially reset the patient’s immune apparatus — following which a maintenance dose is continually administered to sustain desensitization. The therapy, which is set to be christened Palforzia, has been tested in two late-stage trials, in addition to an extension study.
In the 551-patient PALISADES trial in the United States, patients either received Aimmune’s drug or a placebo. In the first tranche of the study, patients received increasingly higher doses of the drug/placebo for about 22 weeks and then were administered with 300 mg (maintenance dose) of Palforzia/placebo per day for approximately six months. At the end of that regimen, patients underwent a ‘food challenge’ in which their ability to ingest a single dose of at least 600 mg of peanut protein was measured.
The efficacy results were dramatic. About 67% of the patients who received the drug (250 of 372 participants) were able to consume 600 mg of peanut protein versus 4% in the placebo group. Over 100 patients enrolled in a follow-on study where they were given Palforzia once a day. Nearly 80% of those patients were able to tolerate at least 1,000 mg of peanut protein, while nearly half managed to withstand a 2,000 mg dose.
“Our hypothesis is…that once we get to somewhere around 3-4-5 years, we will see that the patients are no longer needing therapy and we can stop them,” Aimmune chief Jayson Dallas said in an interview with Endpoints News ahead of the FDA staff review.
But data on the safety side caused some pause — 11.6% of patients (43 participants) given the drug withdrew from the trial due to side-effects, versus 2.4% (3 patients) from the placebo group. Additionally, over the course of the trial 14% (52 patients) of Palforzia-treated patients received an epinephrine shot, versus 6.5% (8 patients) in the placebo group.
In their review, FDA staff underscored these findings after reviewing the totality of the data presented to the agency. “(T)he Palforzia treatment group had an increased number of discontinuations, systemic allergic reactions and reports of eosinophilic esophagitis compared to the placebo-treated group, though both groups followed a peanut avoidance diet,” reviewers noted.
“(T)hese briefing docs look fairly benign,” Baird’s Brian Skorney wrote in a note. “Importantly, the efficacy analysis looks clear as day and there are no new safety concerns raised. We expect the panel to be completely directed towards discussions around epinephrine use and cases of eosinophilic esophagitis (EoE), things we believe the patient/physician community understand well and will willingly accept.”
In his interview with Endpoints, Aimmune chief Dallas offered a comparison. “The side-effect profile that we’re seeing with our product is no more than you would expect if you were treating somebody for grass and pollen allergies, which unlike peanut allergies, are not life-threatening.”
There is also a misconception that if epinephrine is used, it must be due to a severe reaction, he added. “Sometimes parents will give their kids epinephrine if they get a bit of tingling on their tongue…there is zero correlation between using epinephrine and the severity of a reaction.”
Some physicians have long been dosing patients with peanut powder orally, albeit off label, to wean them off their allergies. So why should physicians and payers endorse Aimmune’s product?
Peanuts can carry three different types of proteins that can trigger allergies — and products found on supermarket shelves, such as peanut flour, peanut butter, or cookies embellished with peanuts, contain different concentrations of some or all of these proteins. This is why Aimmune’s product — which carries each protein in equal concentration — is beneficial, Dallas asserted.
In addition, when peanuts are boiled, that dissipates those proteins to an extent. “You run into a situation where somebody believes they are protected. But in fact, they’re not protected,” he said.
Aimmune $AIMT and arch-rival DBV Technologies $DBVT have been locked in a race to the finish line to market their peanut allergy treatments in the United States. Aimmune effectively leapfrogged DBV when the latter rescinded an application to market its Viaskin Peanut patch last year in response to FDA concerns about the state of manufacturing and quality control data submitted.
In July, influential cost-effectiveness watchdog ICER concluded that the existing body of evidence is not strong enough to suggest that AR101 or Viaskin Peanut offer a superior net health benefit versus strict peanut avoidance, in addition to the uncertainty surrounding the long-term effects of either therapy. Both drug developers contested the report.
An FDA decision for AR101 is expected in January 2020, while DBV submitted its marketing application in August. In its calculations, ICER used analyst projections to evaluate each therapy’s long-term cost-effectiveness: AR101 at $4,200/year and Viaskin Peanut at $6,500/year.
Grass and pollen allergy products, after accounting for discounts, cost about $5,000 a year, Dallas said. “And those are for non-life threatening events and so we kind of see that as the floor and we’ll sort of work a little bit around that.”
According to Aimmune, there are more than 1.6 million children and teenagers affected by peanut allergies in the United States, which represents a $1 billion-plus peak sales opportunity. Aimmune’s shares $AIMT rose about 8.6% to $23.97 before the bell on Wednesday.
The so-far untapped market is expected to grow to $4.5 billion in 2027 globally, GlobalData estimates.