Navenibart Shows Favorable Safety, Reduces HAE Attacks in Phase 2 Trial

Philadelphia – Interim data presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting this week offer encouraging news for individuals living with hereditary angioedema (HAE). Results from an ongoing trial suggest that the investigational medication navenibart significantly reduces the frequency of HAE attacks for up to 24 months, with a favorable safety profile. This development could represent a substantial improvement in managing a condition that causes unpredictable and potentially life-threatening swelling episodes.

Hereditary angioedema is a rare genetic disorder characterized by recurring episodes of edema – swelling – in various parts of the body. These attacks can affect the skin, gastrointestinal tract, and airways, leading to significant pain, discomfort, and, in rare cases, asphyxiation. The impact on quality of life can be profound, requiring frequent medical interventions and often leading to anxiety about when and where the next attack might occur.

Navenibart’s Mechanism and Trial Design

Navenibart is a monoclonal antibody designed to inhibit plasma kallikrein, an enzyme central to the biochemical cascade that triggers HAE attacks. By blocking kallikrein, navenibart aims to prevent the production of bradykinin, a potent molecule that causes blood vessels to become leaky, resulting in swelling. The ongoing ALPHA-SOLAR trial, a phase 2 open-label extension study, is evaluating the long-term safety and efficacy of subcutaneous navenibart in adults with HAE-C1INH, a common type of the condition caused by deficiencies or dysfunction in the C1 inhibitor protein.

The interim analysis, with a data cut-off of October 10, 2025, included 29 adults (average age 46, with women comprising 55.2% of the cohort). Participants were divided into two groups: one receiving 600 mg of navenibart followed by 300 mg every three months, and another receiving 600 mg every six months. Researchers assessed changes in HAE attack rates compared to baseline data from the initial ALPHA-STAR trial.

Significant Reductions in Attack Rates Observed

The results demonstrated substantial reductions in HAE attack rates in both dosage groups. The group receiving the 600 mg/300 mg regimen experienced a mean reduction of 91.6% in attack rates, with a median reduction of 96.9%. The group receiving 600 mg every six months also showed significant improvement, with mean and median reductions of 89.9% and 96.6%, respectively. Notably, a high percentage of patients in both groups – 94% in the 3-month group and 92% in the 6-month group – achieved at least a 70% reduction in attack rates. Even more impressively, over half of the patients in each group experienced a reduction of at least 90%, with up to 50% in the 6-month group achieving complete elimination of attacks.

Dr. Adil Adatia, assistant professor at the University of Alberta and director of the University of Alberta Angioedema Centre of Reference and Excellence, highlighted the potential impact of these findings. “One of the unmet needs in HAE is highly efficacious and safe treatments with a highly low treatment burden,” he told Healio. “Historically, these patients required intravenous therapy…we continue to need treatments with low burden of administration, and that’s where I consider navenibart is particularly special.”

Safety and Tolerability

The interim analysis also indicated a favorable safety profile for navenibart. At least one treatment-emergent adverse event was reported in 69% of adults, but serious adverse events were rare. The most common adverse events, occurring in at least 10% of participants, included injection site reactions, nasopharyngitis (the common cold), urinary tract infection, headache, myalgia (muscle pain), and skin laceration. There were no concerning safety signals identified, and injection site reactions were reported at low rates.

Four patients discontinued treatment during the study, but for diverse reasons: one due to a diagnosis of invasive ductal breast carcinoma (the only serious adverse event reported), one due to pregnancy, one due to withdrawal, and one for an undocumented reason. Researchers emphasized that the case of breast cancer was isolated and not necessarily linked to the medication.

What’s Next for Navenibart and HAE Treatment

Navenibart is currently being evaluated in the phase 3 ORBIT-EXPANSE trial, which includes four different dosing arms and a placebo control group. Astria Therapeutics announced the initiation of this trial, representing a significant step forward in HAE treatment development. The primary endpoints of the phase 3 trial will focus on both efficacy and safety, with the goal of securing regulatory approval for the medication.

Dr. Adatia expressed optimism about the future of navenibart, stating, “This product is now in phase 3, and we’re optimistic that that trial will be successful, and hopefully it will be another option with a very low burden that’s safe and efficacious.” The ongoing phase 3 trial will provide further data to confirm these promising interim results and potentially offer a new, convenient, and effective treatment option for individuals living with the challenges of hereditary angioedema. The results of the phase 3 trial will be closely watched by the HAE community and clinicians alike, as they could pave the way for a significant improvement in the management of this debilitating condition.

Further research will be crucial to understand the long-term effects of navenibart and to identify which patients are most likely to benefit from this treatment. Ongoing surveillance and data collection will also be essential to monitor for any rare or unexpected adverse events. As with any new medication, healthcare professionals will need to carefully weigh the potential benefits and risks of navenibart when making treatment decisions for their patients.

Individuals with HAE are encouraged to discuss treatment options with their healthcare providers and to stay informed about the latest research and clinical trial developments. Resources such as the U.S. HAE Association (https://www.haeus.org/) can provide valuable information and support.