Deucrictibant linked to Rapid Symptom Relief in HAE in Phase 2 Trial

A phase 2 RAPIDe-1 trial published in the The Lancet Haematology revealed that oral deucrictibant (20 mg and 30 mg) significantly reduced 4-hour symptom severity scores and accelerated relief in patients with Hereditary angioedema (HAE) when compared to placebo. Median time to meaningful symptom relief improved to ~2.5–2.7 hours versus 8 hours with placebo, which demonstrated faster and more effective control of acute attacks.

HAE attacks can affect the skin, abdomen, and airways, and are driven by excessive bradykinin activity. Current on-demand treatments typically require intravenous or subcutaneous administration, which can delay use or discourage patients from treating attacks promptly. Thus, this study looked into an oral bradykinin B2 receptor antagonist that could be taken quickly at symptom onset.

The phase 2 RAPIDe-1 trial evaluated the safety and effectiveness of deucrictibant in treating acute HAE attacks. Across 38 centers in North America, Europe, and Israel, this study enrolled adults aged 18 to 75 with type 1 or type 2 HAE who had experienced frequent recent attacks.

The trial used a randomized, double-blind, placebo-controlled crossover design. The participants first received assigned doses of deucrictibant (10 mg, 20 mg, or 30 mg) during an attack-free period to assess safety. In the second phase, they treated 3 separate HAE attacks with two doses of deucrictibant and one placebo, without knowing which they were receiving.

These patients self-administered the oral medication within hours of symptom onset, once their symptoms reached a defined severity threshold. The main measure of success was the reduction in symptom severity, which was captured using a composite visual analog scale (VAS-3) four hours after treatment.

Across 147 treated attacks in 62 patients, all three doses of deucrictibant significantly reduced symptom severity compared with placebo. The improvements were consistent across dose levels, with reductions in VAS-3 scores of approximately 15 to 17 points greater than placebo. These results were statistically significant and suggest a meaningful clinical benefit.

The treatment demonstrated a favorable safety profile, where most side effects were mild, with no serious adverse events reported. In the initial phase, a small number of patients experienced headaches or mild upper respiratory symptoms, but these were infrequent. Overall, these findings support further development of deucrictibant as both a preventive and on-demand therapy for HAE. 

Source:

Maurer, M., Stobiecki, M., Valerieva, A., Hakl, R., Staevska, M. T., Bouillet, L., Du-Thanh, A., Kessel, A., Kiani-Alikhan, S., Magerl, M., Reshef, A., Baeza, M. L., Fain, O., Farkas, H., Greve, J., Guilarte, M., Jacobs, J. S., Li, H. H., Lleonart, R., … Aygören-Pürsün, E. (2026). Oral deucrictibant for on-demand treatment of hereditary angioedema attacks (RAPIDe-1): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. Haematology, 13(4), e200–e214. https://doi.org/10.1016/S2352-3026(25)00341-2