Gene therapy for hemophilia B under review in US, Europe

Pfizer seeks approval of fidanacogene elaparvovec for adults with hemophilia B

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Regulatory agencies in the U.S. and Europe are reviewing applications seeking the approval of fidanacogene elaparvovec, an experimental one-time gene therapy being developed by Pfizer for the treatment of hemophilia B in adults.

The U.S. Food and Drug Administration (FDA) expects to complete the review process and to announce its decision in the second quarter of 2024. The European Medicines Agency (EMA) could take up to 210 days (about seven months) to make a decision on the marketing authorization.

If approved, fidanacogene elaparvovec could offer a long-lasting alternative to current treatments for hemophilia B. Instead of relying on regular infusions of clotting factor, patients would receive a single infusion that has the potential to restore the production of the faulty or missing clotting factor within their body.

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“Gene therapy marks a new era of scientific advancement, and if approved, we believe fidanacogene elaparvovec has the potential to transform the lives of people living with hemophilia B who are eligible for treatment,” Chris Boshoff, MD, PhD, said in a press release. Boshoff is chief development officer of oncology and rare disease for Pfizer Global Product Development.

“We look forward to continuing to work with global regulatory authorities to bring this innovative potential treatment to patients as quickly as possible,” Boshoff said.

Hemophilia B is a genetic disease in which a clotting protein called factor IX (FIX) is either faulty or not produced in sufficient amounts. Because this impairs the blood-clotting process, patients are at risk of experiencing excessive bleeding, both spontaneously and after an injury.

“Patients are at the center of our legacy of innovation in hemophilia. Despite significant progress in their treatment, those living with hemophilia continue to experience disruption to daily life and need new options,” Boshoff said.

Fidanacogene elaparvovec, formerly known as SPK-9001, uses a harmless viral vector to deliver a gene that instructs cells to produce the faulty or missing FIX. It is given as a single into-the-vein infusion and is expected to elicit the production of enough FIX to prevent excessive bleeding, potentially eliminating the need for regular FIX infusions.

BENEGENE-2 clinical trial

The submitted applications are based on positive results from a Phase 3 clinical study called BENEGENE-2 (NCT03861273) that involved 45 men with moderate-to-severe hemophilia B who had been receiving regular infusions of FIX for at least six months in a lead-in study (NCT03587116).

All tested negative for preexisting antibodies against the therapy’s viral vector, which could render the gene therapy less effective or ineffective, making them eligible for treatment.

A single dose of fidanacogene elaparvovec was generally well tolerated and resulted in a 71% reduction in the mean annual bleeding rate at month 15 after treatment compared with the six-month lead-in period. The gene therapy also led to a 78% reduction in the rate of bleeds requiring treatment, and to a 92% drop in the annual rate of FIX infusions.

These patients continue to be followed for up to a total of 15 years, including six years in BENEGENE-2 and an additional nine years in a separate Phase 3 study (NCT05568719) that is evaluating the long-term safety and efficacy of fidanacogene elaparvovec.

Fidanacogene elaparvovec has received breakthrough, regenerative medicines advanced therapy (RMAT), and orphan drug designations from the FDA, all meant to support and accelerate its development and regulatory review.