A new study finds encouraging results for those considering the first FDA-approved peanut allergy immunotherapy. It reveals that clinical trial participants who took a daily maintenance dose of the Palforzia OIT drug for two years saw continuing improvement in their ability to tolerate peanut protein, compared to those who used the treatment for a shorter period.
“We wanted to see whether there was an improvement in efficacy and safety over time,” Dr. Daniel Adelman, chief medical officer for Aimmune Therapeutics, the company that developed Palforzia OIT. The findings show there was.
Also of interest, the research team found the immune response in those taking the daily 300-milligram dose for a full two years matured. This allowed those participants to tolerate higher amounts of peanut protein during a food challenge and to experience fewer allergic side effects over time.
This follow-up study was an extension of Aimmune’s Phase 3 PALISADE clinical trial, and involved 261 participants. They were divided into six groups taking the 300-mg dose of Palforzia for different lengths of time (1 year, 1.5 years or 2 years). While some groups took the OIT dose daily, others followed sequences of a dose every day, then every other day. For two groups, that later decreased to twice a week.
Palforzia OIT Duration and Daily Dosing
The results of this followup study show clear effects from the combination of a longer time on Palforzia and daily dosing:
• 72.2% of the group who completed 1 year of daily dosing could successfully consume a single dose of 1,000 mg of peanut protein at the exit food challenge. This success rate was higher than for any of the non-daily dosing groups. (1,000 mg is the equivalent of 3 to 4 peanut kernels.)
• 80% of the group that completed 1.5 years of daily dosing could consume 1,000 mg of peanut protein at the food challenge.
• But 96.2% of the group that completed 2 years of daily dosing could consume 1,000 mg of peanut protein at the food challenge.
• Of note, 81% of the 2-year group went on to successfully consume 2,000 mg of peanut protein at the exit challenge. In fact, since an exit challenge involves taking gradually increasing amounts, this last group cumulatively consumed 4,043 mg over the hours of the challenge. That’s equal to roughly 14 peanut kernels.
As well, participants’ levels of IgE antibodies to peanut declined steadily through the second year of the extension trial. At the same time, their IgG4 levels, a biomarker indicating changes in the immune response, continued to rise.
So what does it all mean? “The implication is that through at least the first two years of treatment, modulation of the immune system is still ongoing; it’s not done,” Adelman told Allergic Living in an interview. “What you’re seeing is an evolution of the immune response to allergenic peanut proteins resulting in improvement in the level that can be tolerated without an allergic response. It suggests a shift towards less immune responsiveness.”
Adelman, who is an allergist, compares the steady maturing of the immune system of patients on long-term treatment with Palforzia to undergoing venom immunotherapy. He says that often a patient’s response to a stinging insect’s venom will lessen over four to five years. “We would expect that the peanut treatment is going to act the same way,” he says. “It’s probably going to continue into Year 3, maybe into Year 4 or beyond.”
What if a Dose is Missed?
But if Palforzia, a biologic powder that contains calibrated amounts of different peanut proteins, is approved to be taken every day – why were some participants in this study taking non-daily doses?
“We wanted to be able to inform patients about what would happen if they missed a dose,” says Adelman. “We were able to demonstrate clearly that there is such a thing as ‘dose forgiveness’. If a patient on long-term maintenance dosing misses a dose or two periodically – say they go off for the weekend, or forget to take a dose. They can safely go back to taking their regular doses after missing one or two, maybe even three doses,” he says.
Aimmune presented the followup study findings at the June 2020 virtual EAACI meeting of European allergists. As in all OIT studies, there were some adverse events reported in this study. Most were classed as mild to moderate, with three patients reporting severe reactions.
Adelman reminds that Palzoria, which the FDA approved as the first licensed peanut allergy treatment in January 2020, is a desensitization protocol. The patient is not “cured” of their allergy and must still avoid intentionally eating peanut-filled foods. But OIT can afford a significant level of protection in case of an accidental peanut exposure.
Availability of Palforzia OIT
The FDA has approved Palforzia OIT as a treatment for peanut-allergic patients aged 4 to 17 years old. The health regulator requires that allergists register for REMS (Risk Evaluation and Mitigation Strategy), in order to prescribe the treatment.
During the COVID-19 pandemic, families have told Allergic Living of waiting to see their allergist in person to discuss food allergy therapy options. And the initial stages of Palforzia OIT treatment do require allergist visits for updosing.
Although most allergists have been restricted to telemedicine visits, Adelman says many are beginning to reopen their offices. “As they do so, they’re preparing to see patients to start them on Palforzia.”
Aimmune has also been working on insurance coverage – “we’ve engaged with payers who cover more than half of of the potential candidates for this treatment in the United States,” says Adelman.
Seven hundred physicians are now REMS-certified to oversee the Palforzia protocol and prescribe the biologic drug. If you’re looking for a registered physician, see the “certified participant locator,” as well as other information on this new treatment at Palforziarems.com.
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