BioCryst Seeks UK Approval of Orladeyo for Preventing HAE Attacks

BioCryst Pharmaceuticals is seeking the approval of Orladeyo (berotralstat) in the United Kingdom as a preventive treatment for sudden and recurrent swelling attacks in people with hereditary angioedema (HAE), ages 12 and older.

If granted, Orladeyo would become the first oral therapy — found in trials to be more convenient than currently approved injections or infusions — in the U.K. for adults and adolescents with HAE.

This approval request, in the form of a marketing authorization application, or MAA, was submitted to the country’s Medicines and Healthcare Products Regulatory Agency (MHRA).

The move follows a positive recommendation recently issued by the Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency (EMA), for the same indication.

The CHMP’s recommendation is now being evaluated by the European Commission (EC), which makes the final decision on approvals for all medicines in the EU. A decision is expected in the coming months.

BioCryst now is seeking Orladeyo’s approval in the U.K. under the MHRA’s new EC Decision Reliance Procedure (ECDRP). That procedure allows a company to make a request for approval in Great Britain within five days of receiving a positive recommendation by the CHMP.

The MHRA then makes a decision on whether to approve a therapy in the U.K. following its approval by the EC.

“The ECDRP provides an opportunity to accelerate the approval of Orladeyo in the U.K. following approval by the European Commission,” Jon Stonehouse, president and CEO of BioCryst, said in a press release.

If approved, Orladeyo would become the first oral daily treatment available in the U.K. for adolescents and adults with the chronic genetic disease. Current preventive treatments are available only as under-the-skin (subcutaneous) injections or into-the-vein (intravenous) infusions.

An oral therapy should be easier to take, and is anticipated to improve patients’ quality of life and independence. Orladeyo already has been approved, at a daily dose of 150 mg, in the U.S. and Japan for the same indication.

“If approved, Orladeyo will provide a much needed oral, once-daily option for many patients and we are excited to be a step closer to making this a reality for them,” Stonehouse added.

Given in capsule form, Orladeyo is a small molecule that blocks the activity of plasma kallikrein, a precursor of bradykinin. Bradykinin, in turn, is an inflammatory molecule whose levels are excessively high in HAE patients, leading to sudden and recurrent bouts of swelling. By suppressing plasma kallikrein, Orladeyo is expected to lower bradykinin levels and prevent these attacks.

The CHMP’s positive recommendation was supported by data from two ongoing trials — the Phase 3 APeX-2 (NCT03485911) and the Phase 2/3 APeX-S (NCT03472040) — which demonstrated that Orladeyo was safe and well-tolerated, as well as effective at lowering the rate of monthly HAE attacks and improving patients’ quality of life.

Orladeyo is currently available in the U.K. through an Early Access to Medicines Scheme (EAMS). This type of scheme allows patients with life-threatening or seriously debilitating conditions to have access to therapies not yet approved for commercial use.