UK Agency Approves Orladeyo to Prevent HAE Attacks

The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing approval to BioCryst Pharmaceuticals’ Orladeyo (berotralstat), as the first oral and daily therapy to prevent acute attacks of hereditary angioedema (HAE) in individuals ages 12 and older.

“HAE UK welcomes the decision from the MHRA to grant marketing authorization for berotralstat in the U.K,” Laura Szutowicz, CEO of HAE U.K., said in a press release.

“An oral therapy that shows effective control of HAE attacks will provide a different treatment choice for clinicians and patients and will assist in improving the quality of life of those living with the condition,” she added.

Following the MHRA decision, the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC) are expected to decide later this year if the medication will be approved for reimbursement under the U.K. National Health Service (NHS).

“This is a significant milestone in furthering our ability to meet the needs of more patients living with HAE,” said Sorena Kiani, MD, an immunologist at Barts Health NHS Trust. “As the first oral, once-daily therapy proven to reduce the number of HAE attacks, today’s news has the potential to offer a convenient new treatment option to improve the lives and outcomes of patients with HAE.”

Orladeyo is expected to improve patients’ quality of life and level of independence, since it is easier to administer compared than injectable medications.

In addition to the U.K., Orladeyo has been approved for the same indication in the European Union, Japan, and the U.S.

Its approvals were supported largely by data from two Biocryst-sponsored clinical trials: the global, Phase 3 APeX-2 trial (NCT03485911) and the open-label Phase 2/3 APeX-S study (NCT03472040).

Data from APeX-2 showed that a single daily dose of 150 mg of Orladeyo was able to significantly reduce the rate of monthly swelling attacks among 121 participants with HAE types 1 or 2, ages 12 and older. The number of monthly attacks dropped by 44% during the first 24 weeks (about six months) of treatment.

This result was sustained, with attacks falling from a mean of 2.9 per month at the start of the trial to one per month by week 48. Attack rates continued to decline in the long-term APeX-S trial, falling to a mean of 0.8 attacks per month.

Orladeyo appeared to be safe and well-tolerated in both studies. Gastrointestinal issues were the most common adverse side effects reported. These tended to occur relatively soon after treatment initiation, became less frequent over time, and usually resolved on their own.

Beyond attack rate reductions, APeX-2 participants also reported “meaningful” improvements in quality of life and overall satisfaction, as well as a lower need for standard on-demand medications.

“With the approval of the first oral, once-daily treatment in the UK,” said Jon Stonehouse, president and CEO of BioCryst, “BioCryst continues to bring Orladeyo to HAE patients and their families around the world.”