Peanut OIT Study Gives Insights Into the Few Patients Who Might Benefit From Therapy

As an FDA advisory committee prepares to meet Friday to discuss an application from Aimmune Therapeutics for AR101, its peanut oral immunotherapy (OIT) product, results of a different phase 2 study were released late Thursday indicating that those with allergies to the legume would have to continue treatment in order to avoid reactions.

Food allergies are incurable and occasionally deadly, with peanut being one of the most ubiquitious. Avoiding the allergen is the only way to manage the allergy, but given the quality of life issues that come with food allergies, companies like Aimmune and DBV Technologies are trying to bring a treatment to market that would cut the risk of a severe reaction.

In general, there are 3 phases to OIT: an initial escalation phase, with gradually increasing daily doses of the allergen, followed by a dose build-up phase and a maintenance phase.

Desensitization occurs when there is temporary increase in the threshold for reactivity; the person with allergies must keep eating their allergen in order to keep reactions at bay. Sustained unresponsiveness (SU)—meaning the treatment sticks—is not known until the allergen is avoided for some time period, and then an oral food challenge is conducted in a medical setting to see if there is a reaction.

Past studies have shown that peanut OIT can desensitize patients and prevent life-threatening allergic reactions, but the optimal duration and dose is unknown. This study, funded by the National Institute of Allergy and Infectious Diseases and published in The Lancet, was a randomized, double-blind, placebo-controlled, single-site trial conducted at the Sean N. Parker Center for Allergy and Asthma Research at Stanford University.¹

The authors said it appears that peanut OIT could desensitize those with peanut allergy to 4000 mg (4 grams) of peanut protein. But ending consumption, or even cutting it back to the smaller amount of 300 mg a day, could increase the likelihood of reacting to peanut. The results could assist in choosing the patients most likely to benefit from OIT, the authors said.

The trial (the Peanut Oral Immunotherapy Study: Safety Efficacy and Discovery, or POISED) enrolled adult and pediatric patients aged 7 to 55 years with confirmed peanut allergy, based on a positive result from a double-blind, placebo-controlled, food challenge (DBPCFC; ≤500 mg of peanut protein), a positive skin-prick test (SPT) result (≥5 mm wheal diameter above the negative control), and peanut-specific immunoglobulin (Ig)E concentration of more than 4 kU/L.

The trial used commercially available peanut flour. Of the 152 patients assessed, 120 were enrolled.

• 60 were assigned to peanut buildup and maintenance, consuming 4000 mg peanut protein through to week 104, and then avoidance
• 35 were assigned to peanut buildup and maintenance on the same 4000 mg dose through week 104, then continued to consume 300 mg for 52 weeks
• 25 were assigned to a placebo (oat flour)

DBPCFCs to 4000 mg peanut protein were done at baseline and weeks 104, 117, 130, 143, and 156.

The primary end point was the proportion of participants who passed DBPCFCs to a cumulative dose of 4000 mg at both 104 and 117 weeks.

Tolerance was assessed after 24 months. Of those participants who received peanut OIT, 83% passed the peanut challenge without an allergic reaction, while only 4% on placebo OIT did so.

Those on OIT who passed the challenge were then randomized to receive either placebo OIT or were switched to a 300-mg daily dose of peanut protein. One year later, more participants on 300-mg peanut OIT (37%) passed the challenge than those on placebo OIT (13%), confirming insights from smaller trials that desensitization is maintained in only a minority of participants after OIT is discontinued or reduced.

The most common adverse events were mild gastrointestinal symptoms and skin reactions, and adverse events decreased over time in all groups. Gastrointestinal symptoms were seen in 90 of 120 patients (50/60 in the group avoiding peanuts and 29/35 in the group that continued with a smaller amount of peanut, and 11/25 in the placebo group). Skin issues were seen in 50 of 120 patients (26/60 in the peanut avoidance group, 15/35 in the continued consumption group, and 9/25 in the placebo group.

Two participants in the peanut groups had serious adverse events during the 3-year study. No treatment-related deaths occurred.

In addition, several blood tests given before OIT could predict which patients had a better chance of achieving SU, namely the IgG4 to IgE ratio, and lower components of peanut allergy markers (Ara h 2 IgE) and basophil activation responses.

In an accompanying editorial, Ronald van Ree, with the University of Amsterdam, Amsterdam, cautioned that OIT probably will not be helpful to those who need it the most: patients who are known to be severely anaphylactic to peanut.²

Besides OIT, other methods that are being tried are sublingual and epicutaneous; the DBV product is a skin patch and is being studied in both peanut and egg.

But if the FDA advisory committee votes in favor of AR101 (to be sold under the name Palforzia, if approved) and the FDA agrees, Aimmune would be the first to market. The AR101 phase 3 trial involved 555 patients aged 4 to 55, although the company is only seeking approval for patients up to aged 17. After 1 year of treatment, 67% of patients could tolerate 600 mg of peanut protein.

References

1. Chinthrajah RS, Purington N, Andorf S, et al. Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study [published online September 12, 2019]. Lancet. doi: 10.1016/S0140-6736(19)31793-3.

2. van Ree R. Sustained unresponsiveness in peanut oral immunotherapy [published online September 12, 2019]. Lancet. doi: 10.1016/S0140-6736(19)31793-3.