Orladeyo approved in EU as first oral treatment to prevent HAE attacks
The European Commission has approved BioCryst Pharmaceuticals“Orladeyo (berotralstat) as the first daily oral treatment to prevent swelling attacks in adults and adolescents 12 years and older with hereditary angioedema (HAE).
Oral preventive treatment should be easier to take than conventional alternatives under the skin and in the vein and, as such, it should improve the quality of life and independence of patients.
“Today, most European HAE patients treat their disease with on-demand therapy or androgens and we believe that the approval of Orladeyo orally, once a day, offers an exciting new opportunity. for these patients to reduce their treatment burden by switching to prophylaxis. [preventive treatment] with Orladeyo, ”said Jon Stonehouse, CEO of BioCryst, in a Press release.
Medicines made from androgens made in the laboratory (male hormones) are used for the long-term prevention of HAE attacks and include Danocrine (danazol), Winstrol (stanozolol) and Oxandrin (oxandrolone).
“Orladeyo is offering people with HAE in Europe and their doctors the first oral non-steroidal option to prevent HAE attacks and is a vital and welcome step in making more treatment options available,” said said Henrik Balle Boysen, executive vice president and chief operating officer of HAE International, a global network of nonprofit patient associations dedicated to improving the lives of people with HAE.
The health authorities in each member state of the European Union, as well as in Iceland, Norway and Liechtenstein, will now decide separately to add Orladeyo to their respective public health programs, which allow patients to access treatments at low cost or free.
Oral therapy is expected to be available to eligible patients in Germany in the coming months, with launches in other European markets to follow soon. Orladeyo is also currently available to eligible patients in France via a temporary authorization for use, issued by the National Agency for the Safety of Medicines and Health Products.
The European Commission’s decision comes about two months after the Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency, recommended the approval of Orladeyo. It also follows similar decisions in the United States and Japan for the same indication.
Orladeyo had previously received expedited designation in the United States, orphan drug and Sakigake designations in Japan, and orphan drug status in Europe – all intended to accelerate its development and review.
A similar marketing application has been filed with the UK Medicines and Health Products Regulatory Agency, in a process allowing such an application following a positive opinion from the CHMP.
In particular, HAE patients aged 12 and over in the UK currently have access to Orladeyo through an Early Medication Access System, which allows patients with life-threatening or severely debilitating illnesses to use therapies not yet approved for commercial use.
Administered as an oral capsule (150 mg) once daily, Orladeyo works by suppressing plasma kallikrein, a precursor of bradykinin – an inflammatory molecule that is overproduced in patients with HAE, causing sudden swelling and seizures. pain.
As such, the therapy is believed to prevent bradykinin levels from rising too high and triggering seizures. The oral route of administration is also expected to ease the burden of standard injectable treatments.
Orladeyo’s regulatory approvals were based on the positive results of two ongoing clinical trials – the placebo-controlled phase 3 APeX-2 trial (NCT03485911) and the 2/3 APeX-S phase open test (NCT03472040).
Both are studying the safety and effectiveness of therapy in preventing swelling attacks in HAE patients 12 years of age and older.
In APeX-2, 121 patients who had had at least two HAE attacks in the two months prior to the start of the study were randomly assigned to a daily Orladeyo capsule (110 or 150 mg) or to a placebo for 24 weeks (almost six months). ).
The 108 participants who completed the treatment entered the extension phase of the trial, in which all received one of the two doses of Orladeyo for at least 24 weeks, totaling one year of treatment or more. for those initially assigned to therapy.
The results showed that the two doses of treatment produced a rapid and significant reduction in the attack rate of HAE, which was maintained for 48 weeks. While more than half of patients treated with Orladeyo saw their attack frequency drop by 50% or more regardless of the treatment dose, the higher dose of 150 mg showed the greatest benefit.
Patients with HAE who completed about a year of treatment with the high dose Orladeyo saw their attack rate drop from an average of 2.9 attacks per month to one attack per month.
Patients receiving the high dose Orladeyo for approximately one year in the APeX-S trial had an average of 0.8 attacks per month.
Patients treated with Orladeyo also reported significant improvements in quality of life and overall satisfaction, in addition to requiring significantly less standard treatment and living more symptom-free days than those receiving placebo.
A joint safety analysis of APEX-2 and APEX-S, involving a total of 342 patients, showed that the treatment was generally well tolerated, that no new safety issues had been identified and that the events the most common adverse reactions were gastrointestinal problems.
These events usually occurred soon after starting treatment, became less frequent over time, and usually went away on their own.