Navenibart at 3- and 6-Month Dosing Reduces HAE Attacks, With Adil Adatia, MD

At the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in Philadelphia, Adil Adatia, MD, assistant professor at the University of Alberta, presented interim data from the ongoing phase 2 ALPHA-SOLAR trial evaluating navenibart, a long-acting monoclonal antibody targeting plasma kallikrein for prophylaxis in hereditary angioedema (HAE) types 1 and 2. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), and secondary endpoints included changes in time-normalized HAE attack rates.

Navenibart is designed for subcutaneous administration every 3 (Q3M) or 6 months (Q6M). In the ALPHA-SOLAR study, both dosing schedules demonstrated favorable safety profiles and substantial reductions in HAE attacks. Median reductions exceeded 95% in both arms, with marked decreases in moderate-to-severe episodes. Injection-site reactions were uncommon, likely due to navenibart’s formulation avoiding citric acid, which is associated with pain in some currently available therapies.

Mechanistically, navenibart is unique among HAE treatments due to its YTE modification, which increases binding to the neonatal Fc receptor. This prolongs the product’s IgG half-life.

“A standard IgG molecule would have a half-life of around 4 weeks, whereas this product can be dosed up to every 6 months,” Adatia said.

On average, novenibart reduced HAE attacks from baseline by 92% (median, 97%) in participants receiving 600 mg then 300 mg Q3M and 90% (median, 97%) in participants receiving 600 mg Q6M. Moderate or severe attacks reduced from mean rates of 1.6 to 0.90 (median, 1.1 to 0.6) in participants receiving 600 mg then 300 mg Q3M and 0.77 to 0.08 (median, 0.53 to 0) in participants receiving 600 mg Q6M.

At data cutoff (October 10, 2025), participants had 7 to 24 months (mean, 12.7) of follow-up. Treatment-emergent adverse events (TEAEs) were reported in 69% of participants, primarily mild and including injection-site reactions, nasopharyngitis, urinary tract infections, headaches, myalgia, and skin lacerations. Only 1 serious adverse event—an invasive ductal breast carcinoma—led to discontinuation. Non-TEAE discontinuations included pregnancy, participant withdrawal, and an undocumented reason.

The study also underscored quality-of-life improvements. With HAE, patients have a reduced quality of life due to the painful nature of the attacks and the worry of having another attack.

“When you have such profound reductions that we saw in this study in the attack rates, you're able to address both factors, so patients start to get used to not having those attacks on a regular basis, and they start to be able to engage in their regular in activities they wouldn't otherwise be engaging in, whether it's going camping in the summertime or traveling,” Adatia said. “And, over time, as they get used to not having attacks, that worry of the next impending attack being serious starts to decrease.”

While the open-label, non-placebo-controlled design of phase 2 limits definitive conclusions, these results informed the ongoing phase 3 ALPHA-ORBIT trial, which includes both Q3M and Q6M dosing arms and a broader population, including adolescents. Adatia emphasized anticipation for the 6-month dosing data and adolescent responses.

“My expectation, and from my experience discussing different treatment options with patients, is they're interested in treatments that are safe, efficacious, and offer the lowest treatment burden,” Adatia said. “I think whether someone is struggling with adherence because they're on a more frequently dosed therapy, whether they're well controlled on their current therapy, or they fall somewhere in the middle, they will find this attractive, and I anticipate that many patients will be interested in it if hopefully it comes to the market.”

Adatia has no relevant disclosures.

References

Adatia A, Sitz K, Yang W, et al. New Submission. Journal of Allergy and Clinical Immunology. 2026;157(2):AB431. doi:https://doi.org/10.1016/j.jaci.2025.12.965