Donidalorsen- new drug for Hereditary Angioedema, reveals phase 3 study

Donidalorsen- a new drug for Hereditary Angioedema

Hereditary angioedema is a unusual dermatological disorder which presents with by episodic, potentially life-threatening swelling of mucocutaneous system. Kallikrein–kinin dysregulation plays a major role in the pathogenesis of this disease. Long-term prophylaxis can stabilize this system but options are limited. Recently phase 3 study of a new drug Donidalorsen in hereditary angioedema was published in New England Journal of Medicine.

This was a phase 3, double-blind, randomized trial, where patients with hereditary angioedema were randomized to receive donidalorsen (80 mg subcutaneously) or placebo once every 4 or 8 weeks. The primary end point was the time-normalized number of investigator-confirmed hereditary angioedema attacks per 4 weeks (attack rate) from week 1 to week 25.

A total of 90 patients received donidalorsen every 4 weeks (45 patients), donidalorsen every 8 weeks (23 patients), or placebo (22 patients). The least-squares mean time-normalized attack rate was 0.44 (95% CI, 0.27 to 0.73) in the 4-week group, 1.02 (95% CI, 0.65 to 1.59) in the 8-week group, and 2.26 (95% CI, 1.66 to 3.09) in the placebo group. The mean attack rate from week 1 to week 25 was 81% lower (95% CI, 65 to 89) in the 4-week group than in the placebo group (P<0.001) and 55% lower (95% CI, 22 to 74) in the 8-week group than in the placebo group (P=0.004). The median reduction in the attack rate from baseline was 90% in the 4-week group, 83% in the 8-week group, and 16% in the placebo group. The mean attack rate during weeks 5 to 25 was 87% lower (95% CI, 72 to 94) in the 4-week group than in the placebo group (P<0.001) and 60% lower (95% CI, 25 to 79) in the 8-week group than in the placebo group.