First Gene Therapy for Haemophilia B Receives FDA Approval

The first gene therapy option for adults with haemophilia B who currently use factor IX prophylaxis, have current or previous life-threatening bleeding, or experience repeated serious spontaneous bleeding episodes is etranacogene dezaparvovec (Hemgenix), which received FDA (US Food and Drug Administration) approval on 22 November 2022.

What Is Haemophilia B?

Haemophilia B is  an inherited bleeding disorder caused by a deficiency of blood clotting factor IX. Without enough factor IX, blood cannot clot properly to control bleeding. The disorder is congenital, meaning it is present from birth, and is rare. The most common form, haemophilia A, affects approximately 12 per 100 thousand people; haemophilia B affects about 3.7 per 100 thousand.

The Result of 20 Years of Research and Human Trials

Gene therapy for haemophilia has been on the horizon for more than 20 years. Despite treatment advances, bleeding episodes and the need for continuing replacement factor IX adversely affect quality of life. This approval offers a new option for people with haemophilia B and represents important progress in innovative therapies for those facing its substantial disease burden.

How Does Hemgenix Work?

Hemgenix, whose active ingredient is etranacogene dezaparvovec, delivers a functional gene through an adeno-associated virus, instructing liver cells to make the clotting factor. Genetic material for producing factor IX is loaded into a carrier virus. According to manufacturer CSL Behring’s press release, these genetic instructions remain in the cell but are not incorporated into the patient’s own DNA.

Gene therapy will cost $3.5 million per patient, making it the most expensive treatment to date. However, lifetime factor IX replacement for a patient with haemophilia B in the United States exceeds $20 million.

FDA Approval Based on the HOPE-B Study

Approval was based on HOPE-B, a single-arm, open-label study in 54 men requiring factor IX replacement. Most people with haemophilia B are male.

During the 18 months after a single Hemgenix infusion, adjusted annual bleeding rates fell by 64% from baseline (P = 0.0002), and bleeds treated with factor IX fell by 77% (P < 0.0001); 98% of patients receiving the full etranacogen dezaparvovec dose stopped factor IX prophylaxis.

Durability remains a concern, but the data are reassuring: mean factor IX activity was 39 IU/dL (39% of normal) at 6 months and 36.9 IU/dL (37% of normal) at 18 months. So far, there is no sign that patients have developed inhibitors following infusion.

Adverse effects were common but largely mild, including headache and flu-like illness, each affecting 13% of participants. Nine patients needed steroids for elevated liver enzymes.

Other gene therapies for haemophilia A include valoctocogene roxaparvovec (Roctavian, BioMarin), which is in development. An FDA approval decision for this treatment is expected in March 2023.