The first oral immunotherapy agent developed to treat peanut allergy in children is on the cusp of market approval after the Allergenic Products Advisory Committee (APAC), convened to advise the FDA, endorsed medical trial data. The therapy is set to be approved by early next year, but significant questions still remain over how effective and long-lasting the treatment will be in real-world conditions.
Palforzia, also known as AR101, has been in development for a number of years. The treatment is fundamentally based on commonly utilized oral desensitization methods suggesting tolerance to allergens can be established by very slowly administering small quantities of an allergen in increasing quantities over a period of time.
Although essentially it is very similar to peanut flour, Palforzia is a manufactured peanut protein with specifically controlled dosages. In its lowest dosages, it comes in capsules as small as half a milligram. These are volumes that are not exactly easy to measure for home users trying the same thing with peanut flour, meaning this kind of oral desensitization method can be very highly controlled.
“We are very pleased that APAC voted in favor of Palforzia,” says Jayson Dallas, CEO of Aimmune the company developing the product. “This is an important day for the children, teens and their families who live with the profound daily impact of peanut allergy. We look forward to continuing to work with the FDA as we move towards a potential approval of Palforzia.”
One of the novel risk management measures included in the licensing application suggests each dose escalation in a Palforzia treatment regime is administered in an approved facility so any acute allergic reactions can be monitored. It is unclear at this stage exactly what will constitute an “approved facility”, however, this particular measure does highlight some of the risks connected to this treatment.
Desensitization therapy for peanut allergens has been the subject of debate among experts for several years. The treatment has been found to require near-permanent long-term administration to maintain efficacy, and one recent metastudy suggested those successfully completing the therapy actually report more real-world allergic responses than those who simply avoided peanuts altogether.
A newly published article in The Lancet reported the results of a randomized, double-blind, placebo-controlled, phase 2 study into the sustained effects of oral desensitization therapy for peanut allergies. From one perspective, the treatment seems to be wholly successful. After 24 months of gradually escalating peanut protein exposure, 83 percent of subjects successfully passed a peanut challenge, compared to only four percent in the placebo group.
While this result certainly seems positive, the study also found if desensitization therapy was discontinued, or the daily peanut protein dose was reduced, the allergenic symptoms quickly returned in the majority of patients. Alongside this finding, other researchers have suggested there are risks of allergic reactions appearing unexpectedly in patients on continuing maintenance doses.
Two out of the nine members of the advisory panel to the FDA voted against the new immunotherapy treatment. Allergy expert from the Scripps Clinic in San Diego, John Kelso, one of the dissenting votes on the panel, suggests the unpredictable nature of allergic responses to the treatment is a red flag.
“Reactions occur unpredictably to previously tolerated doses,” says Kelso in a Science report, while Andrea Apter, the other dissenting voice on the committee, notes a distinct lack of long-term data on the treatment's safety, a concern for a therapy potentially designed for permanent lifetime use.
Despite any ongoing concerns over the ultimate validity of this kind of peanut immunotherapy technique, it is looking like Palforzia will certainly become the first FDA-approved treatment of its type to reach the market. Jayson Dallas, from Aimmune, suggests his team will work with the FDA over the coming months to clarify these safety measures.
“Patient safety has been central to us since the beginning of the Palforzia development program," says Dallas. "We are gratified to be aligned with FDA in our focus on patient safety. We look forward to working with the Agency to finalize our proposals, which we believe will support the safe and appropriate use of Palforzia.”
Source: Aimmune Therapeutics
