1st Gene Therapy for Hem B Granted Priority Review by the FDA

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by Steve Bryson, PhD |

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The U.S. Food and Drug Administration (FDA) has accepted — under priority review — a marketing application for EtranaDez (etranacogene dezaparvovec), an investigational gene therapy for adults with hemophilia B.

The FDA grants priority review to investigational therapies designed to treat serious medical conditions. If approved, the treatment would lead to significant improvements over existing medicines. By accepting the priority review, the agency anticipates a decision on the application in six months instead of the 10 months for standard review.

“The acceptance of etranacogene dezaparvovec for review by the FDA brings us closer to our goal of delivering a life-changing treatment option for people with hemophilia B,” Bill Mezzanotte, MD, executive vice president for CSL Behring, the therapy’s potential marketer, said in a press release. He is also head of research and development and chief medical officer for the company.

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“Etranacogene dezaparvovec, potentially the first gene therapy approved for hemophilia B, further demonstrates CSL’s promise to relentlessly pursue innovative and disruptive technologies when it benefits rare and serious disease patients with unmet medical needs,” Mezzanotte added.

EtranaDez was originally developed by uniQure, which sold its commercialization and licensing rights to CSL. The therapy is designed to raise the levels of factor IX (FIX), the blood-clotting protein that is missing or is defective in people with hemophilia B.

Administered directly into the bloodstream by a single infusion, the therapy uses a modified and harmless adeno-associated virus (AAV) to deliver FIX-Padua — a highly functional copy of the mutated, disease-causing F9 gene. The ultimate goal of the therapy is the long-term prevention and control of bleeding episodes.

The biologics license application (BLA) was supported by data from the ongoing Phase 3 HOPE-B trial (NCT03569891), which is evaluating the efficacy and safety of EtranaDez, formerly called AMT-061, in 54 men with moderate to severe hemophilia B over five years.

At 1.5 years after infusion, top-line data demonstrated the gene therapy significantly increased FIX activity in the bloodstream, achieving a mean of 36.9% of normal and leading to a 64% drop in annualized bleeding rates.

The yearly use of FIX replacement therapy, a standard hemophilia B treatment that provides the missing clotting factor, fell by 97%, and almost all patients (98%) who received a full therapeutic dose stopped using prophylaxis, or preventive treatment.

The data also suggested that nearly all hemophilia B patients may benefit from EtranaDez because the benefits occurred regardless of pre-existing antibodies that target the therapy’s viral AAV carrier, which can limit efficacy.

Most adverse events (80.4%) were considered mild, with no reports of serious adverse events related to the treatment or the occurrence of antibodies against FIX-Padua.

The FDA has granted EtranaDez the designation of breakthrough therapy, which is meant to accelerate the therapy’s development and regulatory review. EtranaDez is also under review in Europe via accelerated assessment, shortening the review period from a standard of seven months to about five months.

“FDA’s acceptance of the etranacogene dezaparvovec BLA for priority review is another pivotal milestone in CSL Behring’s commitment to deliver innovative treatment options that address unmet needs for people living with rare diseases,” added Brahm Goldstein, MD, vice president at CSL. “For more than 35 years, CSL Behring has been at the forefront of innovation in the treatment of hereditary bleeding disorders, offering the largest portfolio of treatment options for the community including a novel, long-acting prophylaxis FIX replacement treatment.

“We look forward to continuing to work with the FDA throughout the review process of the BLA and with our partners at uniQure to potentially provide a new transformative treatment option to people with hemophilia B,” Goldstein said.