Peanut allergy sufferers know they need to stay away from certain foods that can put them in danger. But what about accidental exposure? Even trace amounts of peanut protein in their food or someone else’s can trigger an allergic reaction that sends them to the hospital.
That’s what makes Palforzia, an experimental peanut allergy treatment from Aimmune Therapeutics (NASDAQ: AIMT), a potentially big deal. Palforzia could become the first FDA-approved therapy that reduces peanut sensitivity enough to make those allergic reactions less frequent and less severe. The agency is expected to make an approval decision in January, but only after a panel of outside experts review the drug at a hearing on Friday. Though their vote isn’t binding, the result could swing Palforzia’s fate in one direction or another.
The FDA on Wednesday released briefing documents that give some insight into the agency’s thinking. And the key issue heading into the hearing, according to FDA scientists, is whether Palforzia is safe. FDA reviewers did not question if the drug is effective. But they did note that a small number of patients who took the treatment developed an inflammatory disease sparked as a reaction to foods or allergens. The question panelists will vote on is whether the benefit of treatment is worth that potential risk.
The Aimmune therapy is a powder made from peanut flour. Mixed with food, the therapy is meant to be taken daily. As doses increase over time, a child becomes desensitized to peanut protein. Aimmune says it expects children will need approximately six months to reach the top dose, which they would continue taking daily to stay desensitized. The company says it does not believe missing an occasional dose will affect desensitization.
If the approach sounds familiar, that’s because oral immunotherapy is already practiced by some allergists to desensitize patients to egg, tree nuts, and milk allergies that affect an estimated 4 to 6 percent of US children. For peanut allergies, oral immunotherapy consists of small doses of peanut flour consumed in a drink or with food under medical supervision. The goal is to increase the threshold for triggering an allergic reaction.
There is no FDA-approved protocol or product, however, for oral immunotherapy. Aimmune is vying to become the first. The company says its proprietary formulation contains precise amounts of peanut and food proteins that ensure consistency in the allergen content of each dose.
Aimmune tested its drug in five Phase 3 studies. The biggest test enrolled 555 volunteers ages 4 to 55. Peanut sensitivity was measured by a “food challenge,” in which patients ate increasing amounts of peanut protein until the end of the test or an allergic reaction that caused them to stop. The main goal of the study was to see if patients ages 4 to 17—the target group for the drug—could pass the food challenge with just mild symptoms. After one year, 67.2 percent of the patients in the group that got Palforzia met the study goal, compared to 4 percent of placebo patients.
The efficacy data reported by Aimmune did not persuade the Institute for Clinical and Economic Review (ICER), a non-profit drug-price watchdog group that is increasingly gaining sway with payers. In a July report, ICER said there wasn’t enough evidence to show that the Aimmune drug was better than simply avoiding peanuts. The group said the same about a peanut allergy patch in development by DBV Technologies (NASDAQ: DBVT). ICER’s argument: Neither peanut allergy product reduced the use of epinephrine injections or systemic allergic reactions. What’s more, their likely high price tags may make it difficult for patients to get ahold of them. France-based DBV trails Aimmune in the race to bring a peanut allergy product to the market. The France-based company resubmitted its patch for FDA review last month following a regulatory stumble that sidetracked its application last year.
Critics of ICER, like the Asthma and Allergy Foundation of America and the Allergy & Asthma Network, said the group’s analysis was premature and limited. Some said ICER emphasized the cost of the therapies to payers without complete information. Others said the analysis ignored the therapy’s potential to improve the lives of patients.
In comments submitted in response to the ICER report, Stephen Tilles, Aimmune’s senior director of medical affairs, said it’s not practical for many people to just avoid peanuts. He added that patients in the company’s Phase 3 tests experienced a median 100-fold increase in the amount of peanut protein that they could tolerate—equivalent to going from being able to handle just 1/30th of a peanut to three to four peanuts. That’s significant because in the real world, the median peanut quantity that triggers an allergic reaction is about half a peanut, he said.
Even just avoiding peanuts isn’t a solution, some patients have argued. Speaking at a hearing convened by ICER in June, Tessa Grosso, 16, told the group that her allergy has led to isolation, depression, and anxiety. A peanut allergy therapy could bring quality of life benefits that would be “transformative.”
“Desensitization is valuable,” Grosso said. “Kids like me don’t want to eat a PBJ but we do want to sit with other kids at lunch.”
But will Aimmune’s therapy put kids like Grosso at risk of other health problems? FDA staffers pointed out that 89.1 percent of patients who received Palforzia experienced some sort of side effect, including an allergic reaction. The most common side effects in Phase 2 and 3 testing were gastrointestinal, including itching of the lips, the throat, and vomiting. The frequency of side effects decreased as the study went on, but some of these problems still led to an increase in epinephrine injections compared to the placebo group. Approximately 9 percent of kids on Palforzia and 14.3 percent of adults dropped out of the study due to side effects.
The FDA staff also noted 12 total cases of eosinophilic esophagitis (EoE)—all of them in patients that received the Aimmune drug. EoE occurs when eosinophils, a type of white blood cell, accumulates in the esophagus, leading to difficulty swallowing and chest pain. The total number of EoE cases in Aimmune’s tests was more than RBC Capital Markets anticipated, and analyst Kennen MacKay wrote in a Wednesday research note that the panel’s discussion will likely focus on safety precautions or the potential inclusion of a warning on the drug’s label flagging the risk of allergic reactions. But MacKay added that he still expects the panel will vote to recommend Palforzia’s approval, and that the drug will go on to win a regulatory nod. Investors seem to think so as well: Aimmune shares climbed 13 percent on Wednesday.
The Friday meeting of the Allergenic Product Advisory Committee is scheduled to start at 8:30 a.m.