FDA Approves Orladeyo to Prevent Hereditary Angioedema Attacks

Orladeyo works by binding to plasma kallikrein and inhibiting its proteolytic activity.

The Food and Drug Administration (FDA) has approved Orladeyo™ (berotralstat; BioCryst Pharmaceuticals) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients aged 12 years and older.

Orladeyo works by binding to plasma kallikrein and inhibiting its proteolytic activity. The approval was based on Part 1 data from the double-blind, placebo-controlled phase 3 APeX-2 trial, which assessed the efficacy and safety of Orladeyo in preventing angioedema attacks in patients aged 12 years and older with Type I or II HAE. Patients were randomized 1:1:1 to receive Orladeyo 110mg, 150mg, or placebo once daily with food for the 24-week treatment period. 

Findings showed that Orladeyo 110mg and 150mg were associated with 30% (95% CI, 4.6-48.7; =.024) and 44.2% (95% CI, 23.0-59.5; <.001) reductions, respectively, in the rate of HAE attacks at week 24 compared with placebo. The HAE attack rates per 28 days in the Orladeyo 110mg and 150mg arms were 1.65 and 1.31, respectively, at week 24 (from a baseline of 2.9/month) compared with 2.35 for placebo. Reductions in HAE attack rates were also sustained through 48 weeks (Part 2).

Additionally, Orladeyo 110mg and 150mg met predefined exploratory end points with 51% and 58% of patients, respectively, achieving at least a 50% reduction in HAE attack rates compared to baseline vs 25% of patients in the placebo group. Orladeyo-treated patients also reported meaningful improvements in both quality of life and significant reductions in their monthly use of standard of care on-demand medications.

The most common adverse reactions (incidence of greater than or equal to 10%) reported with Orladeyo were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease. Additionally, an increase in QT prolongation can occur at dosages higher than the recommended 150mg once daily dosage; additional doses or doses higher than 150mg once daily are not recommended.

Orladeyo will be supplied as 110mg and 150mg capsules of berotralstat in 28-count blister cards. The product will be available exclusively through Optime Care Inc, a specialty pharmacy, by the end of December 2020. 

For more information visit orladeyo.com.


1.    BioCryst announces FDA approval of Orladeyo™ (berotralstat), first oral, once-daily therapy to prevent attacks in hereditary angioedema patients. [press release]. Research Triangle Park, NC: BioCryst Pharmaceuticals, Inc; December 3, 2020. 

2.    Orladeyo™ [package insert]. Durham, NC: BioCryst Pharmaceuticals, Inc; 2020.