SAN FRANCISCO — A novel peptide-based immunotherapy for peanut allergy designed to be given as a monthly injection showed a highly favorable safety profile in phase I trial data, researchers said here at the American Academy of Allergy, Asthma & Immunology annual meeting.
Patients treated with PVX108 had no serious adverse events, and no relationship was seen between dosage and frequency or severity of milder events — most notably transient injection site reactions, said Robyn E. O’Hehir, MD, PhD, of Alfred Health and Monash University in Melbourne, Australia.
In a press briefing, O’Hehir explained that unlike whole peanut protein-based immunotherapies, PVX108 utilizes peptides that have been selected from peanut proteins to induce immune tolerance to peanuts.
The idea is that injecting these peptides, in the absence of whole protein allergens, will reprogram allergy-causing immune cells to become tolerant to the allergen with little risk of inducing allergic reactions.
While the strategy’s efficacy is not yet known, O’Hehir said the safety data suggests that the peptide-based immunotherapy is safe, even for patients who are severely allergic.
“While it is still [the] early days, the data suggest that monthly intradermal injections of PVX108 could really transform how we treat peanut allergies, even in patients with severe allergies,” she said. “With greater convenience and a monthly-dosing regimen, we believe that patient adherence could be excellent compared with the daily-dosing regimen required with many immunotherapy protocols.”
The manufacturer-sponsored phase I study was conducted in two phases. In the first phase, the researchers assessed single, ascending doses — 0.05 to 150 nmol — of PVX108 and enrolled eight cohorts of six subjects each.
Subjects were randomized to receive PVX108 or the placebo. Cohorts were enrolled one at a time, starting with a single injection. The dose escalated for each successive cohort, with the eighth cohort receiving the highest dose.
In the second phase of the study, 18 additional subjects were randomized to receive six injections of 150 nmol over a 16-week period.
There were no serious adverse reactions in patients receiving PVX108, and adverse events considered possibly or probably related to treatment were graded mild or moderate, with the majority being transient injection site reactions. None of the adverse events was deemed of clinical concern by the study Safety Review Committee.
There was no relationship between dose level and frequency or severity of adverse events.
Reduced Multiple Anaphylaxis-related Outcomes in Mouse Model
In separate animal studies, also presenting at the meeting, Sudesha Dhar of McMaster University in Hamilton, Ontario, and colleagues, reported that PVX108 significantly reduced multiple anaphylaxis-related outcomes in a mouse model.
Wild-type C57/Bl6 mice were sensitized to peanut and treated with PVX108. They were then challenged with peanut and assessed for clinical anaphylaxis. Mice were sacrificed, serum was collected for specific antibody measurement, and peritoneal lavage was collected for cell differential quantification.
The researchers reported that PVX108 was well tolerated in all animals, and no symptoms of anaphylaxis or adverse events were observed following drug administration. PVX108 treatment significantly reduced anaphylaxis following the peanut challenge.
O’Hehir said phase II studies of PVX108 are in the planning stages and should include children with peanut allergies as well as adults. “The idea is that this therapy can be used in all patients, including children,” she said.
The research was funded by biotechnology company Aravax, which is developing PVX108. The researchers also received support from the Australian Food Allergy Foundation, the Alfred Hospital Trust, and the National Health and Medical Research Council of Australia.
O’Hehir reported being an inventor of the peptide-based immunotherapy and a cofounder and minority shareholder for Aravax Pty Ltd.