The European Medicines Agency (EMA) has agreed to review a request by CSL Behring to approve the potential gene therapy EtranaDez (etranacogene dezaparvovec) for people with hemophilia B.

The request, in the form of a marketing authorization application or MAA, will be reviewed under the EMA’s accelerated assessment, meaning that the review period may be shortened to 150 days (about five months) from a standard seven months.

If approved, EtranaDez, formerly known as AMT-061, will be the first gene therapy available for hemophilia B patients, allowing for long-term control of bleeds after a single dose, and without the need for prophylaxis, or preventive treatment.

“As the first gene therapy candidate for hemophilia B, this pivotal regulatory milestone brings CSL Behring one step closer to delivering on the promise of gene therapy for the bleeding disorders community,” Emmanuelle Lecomte Brisset, CSL Behring’s head of global regulatory affairs, said in a press release.

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“The acceptance of etranacogene dezaparvovec for review by the EMA furthers our relentless pursuit to improve the lives and well-being of those living with hemophilia B and other rare and serious medical disorders,” said Bill Mezzanotte, MD, the company’s executive vice president, head of R&D, and chief medical officer.

“We are proud to work with uniQure to be at the forefront of this scientific advancement which aims to make hemophilia B a secondary part of a patient’s life instead of a constant concern,” Mezzanotte added.

uniQure, the original developer of EtranaDez, sold the therapy’s commercialization and licensing rights to CLS Behring in May 2021. uniQure remains responsible for completing the Phase 3 HOPE-B trial (NCT03569891) – expected to end in March 2025 – and scaling up manufacturing to ensure commercial access to the therapy.

A similar regulatory application is expected to be filed with the US Food and Drug Administration (FDA) in upcoming months.

EtranaDez has been designated a priority medicine by the EMA and a breakthrough therapy by the FDA; these designations are meant to speed the therapy’s development and regulatory review.

Administered through a single infusion directly into the bloodstream, EtranaDez is designed to raise the levels of factor IX (FIX), the missing blood-clotting protein in people with hemophilia B.

It uses a modified and harmless version of the adeno-associated virus variant 5 (AAV5) to deliver FIX-Padua – a highly functional copy of the mutated, disease-causing F9 gene – to patients’ liver cells, the body’s main producers of clotting factors.

Since FIX-Padua produces FIX proteins that are five to eight times more active than normal, the one-time therapy is expected to increase FIX levels and activity, and thereby prevent and control bleeds for long periods of time, possibly several years.

The MAA was supported by data from the ongoing Phase 3 HOPE-B trial, which is evaluating the therapy’s five-year safety and effectiveness in 54 men with moderate to severe hemophilia B – making it the largest gene therapy trial in hemophilia B to date.

Top-line data, at 1.5 years after treatment, showed the therapy significantly increased FIX activity, reaching a mean of 36.9% of normal. This was associated with a 64% reduction in bleeding rates – from more than four bleeds per year to less than two, on average – and a 97% drop in yearly usage of FIX replacement therapy.

In addition, nearly all participants (98%) given a full dose of EtranaDez stopped taking prophylaxis after 1.5 years.

Notably, these benefits were seen regardless of pre-existing antibodies against the therapy’s viral carrier, suggesting that nearly all hemophilia B patients may benefit from EtranaDez.

The gene therapy was generally well-tolerated, with more than 80% of adverse events being considered mild in severity and no reports of treatment-related serious adverse events or development of antibodies against the delivered FIX.

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