Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) causes recurrent, unpredictable swelling attacks. Untreated, they can be severe and last 3–5 days, and they do not respond to antihistamines, steroids, or epinephrine.
Since 2008, treatment has expanded to five approved on-demand drugs and six for long-term prophylaxis, with the goal now being a normal life. But breakthrough attacks still occur even on prophylaxis, which makes early on-demand treatment critical.
The key mediator is bradykinin. In HAE-C1INH, factor XIIa and plasma kallikrein generate bradykinin, which binds the bradykinin B2 receptor on endothelium and increases vascular permeability. Icatibant blocks that receptor and is highly effective, but it must be injected — a real barrier for many patients.
Deucrictibant is also a bradykinin B2 receptor antagonist, but it is taken by mouth. In a phase 3, multicentre, randomized, double-blind, placebo-controlled trial across 24 countries, patients received two randomly allocated treatments — one deucrictibant, one placebo — with a median time from symptom onset to treatment of about 1.5 hours in both arms.
In the 88 patients with HAE-C1INH in the analysis, median time to symptom improvement was 1.28 hours with deucrictibant versus more than 12 hours with placebo (p < 0.0001). The secondary endpoints all favored deucrictibant as well: time to end of attack progression 17.47 vs. 228.67 minutes, substantial symptom relief 2.85 hours vs. more than 12 hours, and complete resolution 11.95 hours vs. more than 48 hours. No safety signals were seen in 201 attacks treated among 113 patients who received at least one dose.
There is also an early broader signal: two patients with HAE-plasminogen, in which bradykinin is generated without factor XIIa/kallikrein, responded similarly. That fits the idea that blocking the receptor downstream could work across bradykinin-mediated subtypes.
Two caveats matter. Bradykinin via this receptor also has cardioprotective effects, so use during reperfusion after acute ischemia could theoretically blunt that protection — a risk that could grow if it were used regularly as prophylaxis. And an oral drug is problematic in severe laryngeal edema when swallowing is impossible, or with vomiting during an abdominal attack.
Still, the combination of fast efficacy, no severe or serious treatment-related adverse events observed, and a swallowed rather than injected route makes deucrictibant a potentially important addition to on-demand treatment — mainly because it lowers the barrier to treating early, when stopping an attack matters most.
Reference:
Zuraw & Christiansen. Deucrictibant: a novel oral on-demand treatment for hereditary angioedema. The Lancet, Volume 408, Issue 10565.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01855-6/fulltext