Biotechnology company Aravax has announced promising topline results from a Phase 2 clinical trial of PVX108, an experimental treatment designed to increase peanut tolerance in children with peanut allergies. Unlike traditional immunotherapies that require regular exposure to allergens, this investigational drug uses targeted protein fragments, known as peptides, to retrain the immune system to tolerate peanuts while minimizing the risk of treatment-induced allergic reactions. Having already received Fast Track designation from the US Food and Drug Administration, PVX108 was administered through once-monthly injections into the skin over the course of a year.
The international trial was conducted at 14 medical centers across the United States and Australia. It included an initial safety cohort of 24 adolescents ages 12 to 17 and a primary efficacy and safety cohort of 71 children ages 4 to 11. In the younger group, participants were randomly assigned to receive monthly injections of either 5 or 50 nanomoles of PVX108 or a placebo in a double-blind study. According to Dr Pascal Hickey, CEO of Aravax, “PVX108 is the first therapy designed to precisely target the root cause of peanut allergy.” He added that the findings raise the possibility of fundamentally altering the course of the disease rather than simply suppressing allergic reactions.
After 12 months of treatment, the trial successfully achieved its primary goal. Children receiving the higher 50-nanomole dose demonstrated a statistically significant improvement in peanut tolerance compared with those receiving a placebo. Their maximum tolerated dose increased 2.4-fold from baseline compared with a 1.2-fold increase in the placebo group. Specifically, 39.4% of children receiving the higher dose tolerated a cumulative 443 milligrams or more of peanut protein during a supervised food challenge—approximately the protein content of one and a half to two peanuts—compared with just 16.7% receiving placebo.
Beyond raising tolerance thresholds, the treatment significantly reduced the severity of allergic reactions during food challenges. At the beginning of the study, all participants experienced moderate or severe reactions at their baseline reactive dose. After 12 months, 67% of reactions at that dose in the higher-dose treatment group were graded as nonexistent or mild, compared with 35% in the placebo group. Children receiving PVX108 also showed statistically significant improvements in peanut skin prick tests and reported reduced emotional impacts associated with living with food allergies, suggesting benefits that extend beyond physical tolerance alone.
PVX108 also demonstrated an encouraging safety profile throughout the year-long study, with 96% of the younger participants completing treatment and the primary endpoint food challenge and no withdrawals attributed to the study treatment. No treatment-related allergic adverse events, including anaphylaxis, or treatment-related serious adverse events were reported in either dosing group. Treatment-related side effects were uncommon, occurring in 13% of children receiving the higher dose, and none exceeded moderate severity. Reactions at the injection site were the most frequently reported treatment-related side effects.
Perhaps the most promising finding emerged six months after treatment ended. Follow-up food challenges at the 18-month mark showed evidence that improvements in peanut tolerance were maintained or, in some cases, increased despite the absence of ongoing injections. These findings suggest PVX108 may have disease-modifying potential, although longer-term follow-up and larger studies will be needed to determine how durable the benefits are. Dr Brian P Vickery, Chief of Allergy and Immunology at Children’s Healthcare of Atlanta, noted that “once-monthly administration of PVX108 may offer the possibility of retraining the immune response to peanuts without burdensome precautions,” adding that, if confirmed in larger studies, the approach could represent a “significant leap forward for the food allergy field.” However, the findings do not establish that patients receiving PVX108 can safely discontinue standard allergy precautions, including allergen avoidance and access to epinephrine.
Looking ahead, 87% of the children who completed the initial study elected to enroll in a 12-month open-label extension, with additional results anticipated in the second half of 2027. The Phase 2 findings are scheduled for presentation at the American College of Allergy, Asthma and Immunology annual meeting in Phoenix, Arizona, on November 14, and at the EAACI FAAM-EUROBAT-ISMA meeting in Utrecht, the Netherlands, on November 20. Reflecting on the milestone, Aravax Chief Scientific Officer Dr Sara Prickett emphasized that the participating children and their families “are the drivers of our commitment to PVX108 and its continued development,” as the company plans further clinical development and advances its pipeline of treatments for other food allergies. While the results are encouraging, they remain preliminary company-reported findings from a relatively small Phase 2 trial, and PVX108 has not yet been approved for clinical use.
