CSL Behring Secures Conditional Approval in Europe for Hemophilia B Gene Therapy
First-Ever Gene Therapy for Hemophilia B in Europe
The European Union Executive Committee granted conditional marketing authorization for CSL Behring GmbH's Hemgenix (etranacogene dezaparvovec) on February 20, 2023. This decision followed a positive opinion issued by the EMA's Committee for Medicinal Products for Human Use (CHMP) on December 15, 2022. The indication is for adults with severe or moderately severe hemophilia B who do not have a history of factor IX inhibitors. Hemgenix is a one-time intravenous gene therapy that delivers a high-activity Padua variant human coagulation factor IX gene via a recombinant adeno-associated virus 5 (AAV5) vector to liver cells. Its clinical value in replacing lifelong factor IX prophylaxis with a single dose provided the rationale for early access.
Efficacy Demonstrated in HOPE-B Phase 3 Trial
The approval was based on the open-label, single-arm HOPE-B Phase 3 trial, which included 54 adult males with severe or moderately severe hemophilia B. The adjusted annualized bleeding rate (ABR) after 7–18 months post-dosing decreased from 4.19 to 1.51, a 64% reduction, meeting non-inferiority criteria. At the time of EMA evaluation, 96% of patients had discontinued routine factor IX prophylaxis, demonstrating both bleeding control and reduced treatment burden. A 5-year follow-up showed that 94% of 51 patients remained off regular prophylaxis, with an average factor IX activity of approximately 36%, reinforcing the therapy's durability.
Conditional Approval and Commercialization Challenges
Conditional approval means that ongoing data on the duration of effect and long-term safety must continue to be collected. CSL must submit ongoing studies and patient registry data to the EMA. The U.S. FDA granted full approval for Hemgenix on November 22, 2022, and no advisory committee (AdComm) meeting was held, as the issues were deemed not significant. The U.S. list price is set at $3.5 million per dose, and in Europe, country-specific pricing and reimbursement negotiations, along with access to administration centers, will determine the speed of revenue conversion. SEC filings indicate that global sales of factor IX-containing therapies in 2018 were at least $1.5 billion, highlighting the economic potential for a one-time gene therapy to replace the existing market.
Strengthened Market Position Following Competitor Withdrawal
Standard-of-care treatments include CSL's Idelvion (albutrepenonacog alfa, factor IX) and Sobi and Sanofi's Alprolix (eftrenonacog alfa, factor IX), both extended half-life formulations. Direct gene therapy competitor Pfizer's Beqvez (fidanacogene elaparvovec, Padua variant factor IX) received conditional approval in the EU on July 24, 2024, but was not launched and had its approval withdrawn on May 15, 2025, for commercial reasons. As a result, Hemgenix retains its position as the only approved and commercially available gene therapy for hemophilia B in Europe. However, long-term follow-up requirements, ultra-high pricing, and a limited eligible patient population remain key constraints in translating clinical superiority into revenue.
Hemgenix demonstrated a 64% reduction in adjusted ABR from 4.19 to 1.51 and led to the discontinuation of regular factor IX prophylaxis in 96% of patients at the time of approval evaluation, providing a foundation to shift the at least $1.5 billion factor IX therapy market to a one-time dosing model. In the short term, CSL Limited (ASX: CSL) is positioned to defend patient-specific treatment options with both Idelvion and the gene therapy, while uniQure N.V. (NASDAQ: QURE) secures the basis for up to $160 million in milestones and tiered double-digit royalties. In the medium to long term, the 5-year durability data from Phase 3 and Beqvez's EU withdrawal strengthen Hemgenix's competitive position. However, the $3.5 million U.S. list price and country-specific reimbursement negotiations will be decisive factors in patient access and revenue trajectory. For researchers and industry, the long-term efficacy, liver safety, and immune response data from AAV5-based liver-targeted gene delivery will set precedents for the development criteria and payment models of subsequent hemophilia and rare disease gene therapies.
Source: EMA (ema)