FDA Approves First Oral, Once-daily Therapy to Prevent HAE Attacks

Rare Daily Staff

The U.S. Food and Drug Administration approved BioCryst Pharmaceuticals’ oral, once-daily therapy Orladeyo to prevent attacks of hereditary angioedema in adults and pediatric patients 12 years and older.

Hereditary angioedema (HAE) is a rare, genetic disorder that results in recurring attacks of swelling in various parts of the body, including the abdomen, face, feet, genitals, hands, and throat that can be can debilitating and painful. Attacks that obstruct the airways are potentially life-threatening due to the risk of asphyxiation.

Orladeyo is a novel oral plasma kallikrein inhibitor being developed for both prophylactic and acute treatment of HAE attacks. Kallikrein is an enzyme that is chronically uncontrolled in people with HAE. One capsule of Orladeyo per day works to prevent HAE attacks by decreasing the activity of plasma kallikrein.

“Orladeyo offers people with HAE and their physicians the first orally administered non-steroidal option for preventing HAE attacks and represents an important and welcome step in making more treatment options available to physicians and patients,” said Anthony Castaldo, president and CEO of the US Hereditary Angioedema Association.

In the pivotal phase 3 APeX-2 trial, Orladeyo significantly reduced attacks at 24 weeks, and this reduction was sustained through 48 weeks. HAE patients who completed 48 weeks of treatment (150 mg) saw reductions in their HAE attack rates, from a mean of 2.9 attacks per month at baseline to a mean of 1.0 attacks per month after 48 weeks of therapy. In the long-term open label APeX-S trial, patients completing 48 weeks of therapy (150 mg) had a mean attack rate of 0.8 attacks per month.

Orladeyo was safe and well tolerated in both trials. The most frequently reported adverse reactions in patients receiving Orladeyo compared with placebo were gastrointestinal reactions. These reactions generally occurred early after initiation of treatment with Orladeyo, became less frequent with time, and typically self-resolved.