AMSTERDAM (FRONTLINE MEDICAL NEWS)A targeted oral medication for the prevention of potentially life-threatening episodes of hereditary angioedema produced a clinically meaningful reduction in attack frequency in a double-blind, placebo-controlled phase II study.

“This is very exciting. Without exaggeration, this is one of the deadliest and most challenging diseases that we deal with as dermatologists. What these patients want is oral prophylaxis, and we’ve got proof of concept with this trial. This is a bright new future for patients with hereditary angioedema, ” Dr. Marcus Maurer said in presenting the results of the OPuS-1 (Oral Prophylaxis for Hereditary Angioedema) trial at the annual congress of the European Academy of Dermatology and Venereology.

The investigational agent BCX4161 is a potent oral inhibitor of plasma kallikrein, which plays a key role in hereditary angioedema (HAE) by inducing vasodilation, edema, and nonvascular smooth muscle contraction.

OPuS-1 was a double-blind, randomized crossover study in which 24 patients with severe HAE were assigned to 4 weeks of BCX4161 at 400 mg or placebo three times daily, then switched to 4 weeks of the other regimen after a washout period. Participants averaged 42 years of age with a mean 32-year duration of HAE. At enrollment, they averaged 1.5 attacks per week, and they had a mean of 1.2 emergency department visits for HAE during the previous year. Twenty of the 24 patients had a history of one or more laryngeal attacks, the most serious manifestation of HAE, which eventually results in death by strangulation in roughly 30% of affected individuals, explained Dr. Maurer, professor of dermatology and allergy at Charité University Hospital in Berlin.

The primary outcome was the adjudicated attack rate, which was 1.27 attacks per week with placebo and a significantly lower 0.82 per week while patients were on BCX4161. Attacks averaged 20-23 hours in duration. Three patients were attack free on BCX4161; none was attack free during the placebo phase.

The novel agent also resulted in significant improvement on the secondary endpoints of quality of life and disease activity. Quality of life, as measured by the Angioedema Quality of Life questionnaire, improved by 8.4 points from baseline during active treatment, compared with 0.5 points with placebo. Disease activity, as assessed by the Angioedema Activity Score, or AA28, decreased while patients were on BCX4161, with a mean score of 21.4 vs. 28.8 with placebo.

The tolerability and side effects of BCX4161 were the same as with placebo. The rate of treatment compliance was 98%.

HAE is a rare and debilitating genetic disease with an estimated prevalence of 1 in 50,000. The most common symptoms include asymmetric swelling of the hands, feet, face, genitals, airway, and GI tract. HAE is caused by a deficiency of the C1 inhibitor, with resultant accumulation of bradykinin. By inhibiting plasma kallikrein, BCX4161 curbs bradykinin production.

“This disease has nothing to do with histamine or mast cells. This is not allergy or urticaria,” Dr. Maurer noted.

OPuS-2, a larger 12-week trial, is planned.