Jones, an allergist at the Arkansas Children’s Hospital, who is also on the scientific advisory board for Aimmune Therapeutics, the company that developing the peanut biologic oral therapy, provided more context to the study’s success, as previously reported in Allergic Living. The big takeway: this therapy is safe, and it works.
At the end of the trial, half of those being treated with the peanut biologic could consume a dose of 1,000 milligrams of the peanut biologic drug. (That’s about three to four peanut kernels). The median dose of peanut they could tolerate starting the study was only 10 mg.
“The median dose tolerated was 100-fold higher in the [treatment] group at exit compared to at entry, and symptom severity and epinephrine use at exit challenge were blunted,” Jones reported to the meeting of the American Academy of Allergy, Asthma and Immunology and World Allergy Organization.
Aimmune plans to file for FDA-approval at the end of this year, pending the results of two other Phase 3 studies, with an aim to roll out the peanut biologic product in the latter half of 2019. Allergists at the conference told Allergic Living they were encouraged by the prospect of FDA approval and finally having a sanctioned therapy to offer peanut-allergic patients that would curtail the risks of accidental peanut exposures and improve quality of life.
The therapy, dubbed AR101, takes the concept of oral immunotherapy, which is currently being studied in clinical trials and used by some allergists in private practice to desensitize patients to allergens, and makes it easily available for any allergist to offer to peanut-allergic patients.
Rather than simply using peanut flour, patients take a carefully produced and measured dose of powder that has a specific amount of different proteins in it. The doses are held in a capsule (or sachet, for larger doses) until the patients mixes it with food. The amount of peanut protein starts out minuscule, at 1/2 a milligram, and increases gradually to reach 300 mg by six months. In this study, the patient stayed on that dose for another six months, and then underwent an oral challenge to peanut.
To satisfy the FDA, researchers were looking for a key amount – 600 mg of peanut powder in a single dose – that patients could tolerate at the end of the year. Sixty-seven percent of participants on AR101 ate this amount with no symptoms (or extremely mild ones) compared to 4 percent of participants who were on the placebo. “The difference between these groups was 63.2 percent, which was highly statistically significant,” says Jones.
The study, called PALISADE, is the largest OIT study conducted to date, and the first to accept patients with a history of severe or life-threatening reactions. Almost three-quarters of the participants had a prior history of anaphylaxis to peanut, over half had asthma and two-thirds had multiple other food allergies. “These data suggest that AR101 could potentially be useful in the treatment of peanut allergy in a highly sensitive population of children and adolescents to prevent allergic reactions,” Jones said.
The treatment was not without some side effects. Twelve percent of patients in the treatment group discontinued due to adverse events, including chronic gastrointestinal symptoms and hypersensitivity reactions. One patient was diagnosed by biopsy as having eosinophilic esophagitis (EOE). There was one instance of severe anaphylaxis, early in the maintenance phase, in the treatment group. At least six others withdrew due to mild or moderate anaphylaxis.
“Overall, the safety profile of AR101 was similar to previous studies of oral immunotherapy with the frequency and severity of hypersensitivity reactions as was predicted prior to the study and as expected. The 6.7% rate of GI withdrawals and the one case of EoE for the population of almost 500 children was lower than expected,” said Jones.
The study also included a small number of adults who, among those who completed the study, had a similar success rate. Full data from those participants will be presented at the European Academy of Allergy and Clinical Immunology meeting in May 2018.
At this time, Aimmune is only seeking approval for use in peanut-allergic children aged 4 to 17. The treatment would need to be delivered by an board-certified allergist trained on the protocol.
For full coverage of the AAAAI/WAO joint congress, see here.