Extended half-life hemophilia B therapies: what are the key selection criteria?

Recently, many hemophilia B therapies with extended half-life have been introduced into Korea’s clinical field.

Hemophilia is a rare bleeding disorder caused by a blood clotting factor deficiency. Especially severe patients face many difficulties in daily life due to spontaneous bleeding and joint damage. The World Federation of Hemophilia (WFH) recommends preventive treatment to maintain blood clotting factor activity as the standard of care.

Hemophilia is divided into two types—hemophilia A and hemophilia B—which require different treatment approaches. This is due to differences in the distribution of factors 8 and 9. Factor 8 is mainly distributed in the blood vessels, while factor 9 is more distributed in extravascular areas, where it plays an important role in tissues, muscles, and joints.

Because of these characteristics, hemophilia B patients are less prone to bleeding and arthropathy than hemophilia A patients, and strategies for treating hemophilia B should consider the extravascular distribution of factor 9.

In recent years, extended half-life agents have become available, improving the convenience of prophylaxis and the quality of life of people with hemophilia B. Previously, the standard half-life treatment required 104 days per year (based on twice-weekly dosing), but the new extended half-life formulations provide prophylaxis with only one dose every seven to 14 days, significantly improving the convenience of treatment.

The first extended half-life product introduced in Korea is Sanofi's Alprolix, a long-acting treatment consisting of factor 9 and Fc fusion protein. Alprolix, approved by the Ministry of Food and Drug Safety (MFDS) in 2017 and launched in March 2020, was made available to more patients with hemophilia in August last year when the prescription code for the drug was completed at the clinic affiliated with the Korea Hemophilia Foundation.

Alprolix is characterized by extending the half-life of factor 9 by about 2.4 times compared to the previous one through Fc fusion protein technology, so it stays in the body for a long time and does not accumulate through natural degradation.

In July, CSL Bering Korea's long-acting treatment Idelvion won health insurance coverage. Idelvion gained approval from the Ministry of Food and Drug Safety in March 2020. Its recommended dose is once weekly, although patients who are well controlled on a weekly regimen can be dosed every 10 or 14 days. In some adult patients 18 years of age and older, it may be administered up to 21 days apart.

“It is important to understand the difference between factor 8 and factor 9 in treating hemophilia,” said Professor Lee Jae-hee of the Department of Pediatric Hematology and Oncology at Chungbuk National University Hospital. “Preclinical data from Alprolix shows that factor 9 has a consistently significant effect on joints through extravascular distribution. “In addition to half-life, various pharmacokinetic variables, such as clearance and extravascular distribution, should also be considered when treating hemophilia B.