Deucrictibant shows long-term efficacy, safety in treatment of hereditary angioedema

Key takeaways:

• One adverse event was recorded in the treatment group.
• An attack rate reduction of 93% was seen in the treatment group.
• Attack rates remained low for more than 1.5 years.

Deucrictibant was well tolerated in daily 40 mg doses and showed no new safety signals among patients with hereditary angioedema, according to a poster presented at Bradykinin Symposium 2024 in Berlin.

Deucrictibant is a B2 receptor antagonist that is selective and orally administered for prophylactic and on-demand treatment for hereditary angioedema (HAE) attacks, Marc A. Riedl, MD, clinical director, U.S. HAEA Angioedema Center, University of California at San Diego, and colleagues wrote.

There is currently an unmet need for prophylactic treatments that have injectable-like efficacy, are well tolerated and easy to administer, according to the researchers.

In this ongoing phase 2 CHAPTER-1 open-label extension (OLE) study, deucrictibant 40 mg per day was given to participants in order to examine the long-term safety and efficacy of the drug against HAE attacks.

Eligible participants were aged 18 to 75 years, had a diagnosis of HAE 1 or 2, were not taking any other prophylactic medications and experienced at least three HAE attacks within 3 months before screening or more than two attacks during screening.

In part 1 of the study, which was a randomized controlled trial (RCT), participants received deucrictibant 20 mg dosed as 10 mg twice daily, deucrictibant 40 mg dosed as 20 mg twice daily, or daily placebo for 12 weeks.

In part 2, the OLE period, 11 participants from the 20 mg group, 10 from the 40 mg group and nine from the placebo group received 40 mg deucrictibant in two 20 mg daily doses.

Among the 30 participants (mean age 39.1 years, 60% female), the mean treatment duration was 12.83 months (standard deviation, 5.03).

The 40 mg daily doses of deucrictibant were well tolerated among participants, with one treatment-emergent adverse event of tooth discoloration considered related to treatment. There were no serious or severe treatment-emergent adverse events and none led to study discontinuation, study withdrawal or death.

HAE attack rates remained low with long-term daily deucrictibant 40 mg of more than 1.5 years. An attack rate reduction of 93% was observed in the OLE compared with the RCT study baseline (least square (LS) mean, 0.15 vs. 2.16, respectively).

Researchers also observed a reduction in the rate of moderate and severe HAE attacks in the OLE participants compared with the RCT placebo group (LS mean, 0.07 vs. 1.5). The rate of attacks treated with on-demand medication was also low in the OLE study group compared with the RCT placebo (LS mean, 0.07 vs. 1.41).

The study authors concluded that the results of the OLE study show that deucrictibant may be a safe and effective treatment for the prevention of HAE attacks as well as a viable prophylactic therapy for HAE.