The peanut-powder oral treatment Palforzia became the first FDA-approved immunotherapy for food allergy in late January 2020. The peanut (Arachis Hypogaea) allergen powder-dnfp is designed to desensitize peanut allergies in children and adolescents, and prevent potentially life-threatening reactions.
Within 6 weeks of its approval for use in children, age 4-17 years, most of the U.S. shut down due to the pandemic, and it was widely agreed that the timing of the immunotherapy’s arrival on the U.S. market was less than optimal.
A little over a year later, it is still unclear to what degree physicians, parents, and patients will embrace peanut allergy immunotherapy (IT), along with IT for other food allergies when they become available. The topic was front and center at the American American Academy of Allergy, Asthma & Immunotherapy (AAAAI) virtual meeting, with newly reported data from pivotal Palforzia trials, and data on the investigational epicutaneous IT treatment Viaskin Peanut.
Even pre-pandemic, there were questions as to whether FDA-approved, standardized IT therapy would be widely accepted, given the high treatment burden and more.
Edwin Kim, MD, director of the University of North Carolina Food Allergy Initiative in Chapel Hill, told MedPage Today that it may not be clear for a while to what extent the treatment is accepted.
“COVID-19 shined a spotlight on the downsides of a treatment that requires so many physician visits,” he said. “If it was an easy treatment we might have seen more uptake, but it’s not an easy treatment.”
Thomas Casale, MD, of the University of South Florida in Tampa, presented pooled data from six trials — PALISADE 1, RAMSES, ARTEMIS 2, and three open-label extension trials — in more than 1,100 children that showed that three out of four patients achieved the 300-mg maintenance dose of the oral IT (n=938), while more than half of patients were on the treatment for at least a year as of July 31, 2020.
A total of 94 patients stayed on the treatment for 3 years at a maintenance dose of 300 mg after up-dosing. A total of 13.3% patients discontinued the study due to adverse events (AEs), with gastrointestinal symptoms reported as the most common reason for withdrawal.
Most of these AEs occurred during the first 6 months of oral IT, with just 1.4% and 5.8% of long-term Palforzia users reporting moderate and mild treatment-related AEs, respectively, at the end of year 3.
During approximately 3.5 years of treatment, 1.2% of long-term users (n=14) experienced a treatment-related severe systemic allergic reaction. All of these reactions were successfully treated with epinephrine, Casale said.
The maintenance dose of 300-mg peanut protein is equivalent to eating one peanut. “If you are able to tolerate 300 mg of peanut you can effectively prevent about 95% of adverse reactions,” Casale said. “So 300 mg is an important indicator of some degree of safety.”
He noted that many of the severe allergic reactions occurred among children who exercised close to the time they took the oral IT. Exercise is not recommended during the hour before dosing and for several hours after the uploading phase of treatment.
Casale acknowledged to MedPage Today that Palforzia’s uptake in the past year has been slow because “A treatment like this requires a lot of contact with the patient.”
The dosing schedule generally requires around a dozen physician visits that last about 30-90 minutes each. A single-day initial dose escalation phase is required with clinician-observed up-dosing every 2 weeks to achieve 11 increasing dose levels. This is followed by a daily home-dosing maintenance phase.
“I think that after COVID is gone, which hopefully will be sooner than later, the uptake of this type of therapy will be a lot greater than it is today,” Casale said.
‘Things We Would Like to Work On’
While the demand for standardized food allergy treatments remains unclear, studies examining the safety and efficacy of peanut IT have generally been reassuring.
Post hoc analysis from the 12-month phase III PEPITES trial of the epicutaneous IT (EPIT) Viaskin Peanut suggested that in addition to increasing the reactivity threshold in kids, ages 4 to 11 years, with peanuts allergies, daily EPIT for a year (250 µg dose) may also reduce the severity of allergic reactions.
In August 2020, the FDA rejected DBV Technologies’ application for approval of Viaskin Peanut, citing concerns about the impact of patch-site adhesion on efficacy. The agency requested product modifications and additional studies.
In preclinical data presented at AAAAI, Viaskin Peanut was found to reduce mast-cell degranulation through increases in immunoglobulin G (IgG) receptor expression in a mouse model of cashew allergy.
In an AAAAI session devoted to lessons learned from food allergy IT clinical trials, Christina Ciaccio, MD, chief of allergy/immunology and pediatric pulmonology and sleep medicine at the University of Chicago, outlined the many challenges remaining.
“We have numerous forms of immunotherapy that are currently under investigation, including multi-food oral immunotherapy, epicutaneous immunotherapy, sublingual immunotherapy, biologics, vaccines and microbiome modulating agents,” she said. “The fact that only one allergen-specific IT treatment for food allergy has been approved by the FDA highlights the remaining challenges.”
“For those that do have peanut allergies, this treatment [IT] is not universally effective and it is not universally available,” Ciaccio said. “The side effects are too frequent, and as it stands right now, this is a life-long therapy. These are all things we would like to work on.”
The Palforzia trials were funded by Aimmue Therapeutics. The Viaskin Peanut trials were funded by DBV Technologies.
Kim disclosed relevant relationships with, and/or support from, Aimmune Therapeutics, AllerGenis, ALK, Duke Clinical Research Institute, Belhaven Pharma, Nutricia, the NIH, Food Allergy Research & Education, and the Wallace Research Foundation.
Casale disclosed relevant relationshiops with Astra-Zeneca, Sanofi Regeneron, Genentech/Asthma Pathogenesis, GlaxoSmithKline, Novartis, Genentech, Amgen; Siolta, and Thermo Fischer/Allergy Diagnostics.
Ciaccio disclosed relevant relationships with Novartis, Astra-Zeneca, Alk, Genentech, Sanofi-Genzyme, and DBV Technologies.