BW-20805 Reduces HAE Attacks in Phase 2 Trial, With Markus Magerl, MD

Late-breaking data presented at the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in Philadelphia suggest that BW-20805, an investigational therapy designed to suppress plasma prekallikrein production through a targeted RNA interference approach, may offer long-acting prophylaxis for patients with hereditary angioedema (HAE). Phase 2 data show BW-20805 achieved high rates of attack-free outcomes at dosing intervals up to 6 months; the highest dose (600 mg) eliminated HAE attacks.

“This is very amazing data, and it's comparable or even superior to existing therapies,” investigator Markus Magerl, MD, from Charité-Universitätsmedizin Berlin, told HCPLive.

BW-20805 consists of a small interfering RNA conjugated with N-acetylgalactosamine, enabling targeted delivery to hepatocytes via the asialoglycoprotein receptor. Once inside liver cells, the molecule inhibits messenger RNA responsible for producing prekallikrein, the inactive precursor of plasma kallikrein.

The ongoing open-label, international, multicenter phase 2 trial enrolled adults with HAE type 1 or type 2 and evaluated 3 dosing regimens of the investigational therapy: 600 mg every 24 weeks, 300 mg every 24 weeks, and 300 mg every 12 weeks. At the time of the interim analysis, 14 participants had been dosed, and 10 had post-dose efficacy data beyond day 29. Among those patients, 80% remained completely attack-free during the observation period.

Across dosing groups, the therapy demonstrated substantial reductions in attack frequency. The highest dose cohort experienced a 100% reduction in time-normalized HAE attack rate, while reductions of 89% and 87% were observed in the 300-mg every-24-week and every-12-week groups, respectively.

Within the first month after administration, prekallikrein levels declined by approximately 90% to 97%, depending on the dosing regimen. These reductions remained stable throughout follow-up in participants who continued in the study.

“The drug BW-20805 is doing what we expect to do, reducing the plasma kallikrein activity and reducing it by more than 90% in a very stable way,” Magerl said.

“This shows that the drug is doing exactly what it is designed to do,” Magerl said. “It reduces plasma kallikrein activity in a very stable way.”

The therapy also demonstrated a favorable safety profile in early analyses. Most reported adverse events were mild and transient, primarily consisting of injection-site reactions. The interim analysis observed no treatment-related serious adverse events.

If these findings are confirmed in larger studies, BW-20805 could offer a significant shift in treatment convenience for patients with HAE. Unlike other prophylactic therapies, which often require monthly injections, BW-20805 has an extended dosing interval of every 3 to 6 months.

Despite the encouraging results, Magerl cautioned that the current findings come from a relatively small phase 2 cohort. Additional data will be needed to confirm the durability of efficacy and further characterize long-term safety. Future analyses will focus on longer follow-up periods, potential delayed adverse events, and whether pharmacokinetic data support even longer dosing intervals.

“The data from the phase 2 study is very promising,” Magerl said. “I'm looking forward to [seeing] this data…when the [phase 2] study has been finished and especially the phase 3 data.”

Magerl has no reported disclosures.

References

Zhi Y, Zhao X, Zhu R, et al. Significant HAE Attack Reduction with BW-20805, a Long-Acting Prophylactic Injection- An Ongoing Phase 2 Study in Adult with Hereditary Angioedema. Journal of Allergy and Clinical Immunology. 2026;157(2):AB426. doi:https://doi.org/10.1016/j.jaci.2025.12.948