In Consultation with FDA, Freeline Modifies Hemophilia B Gene Therapy Trial

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London-based Freeline Therapeutics announced that after receiving feedback from the U.S. Food and Drug Administration (FDA), it was modifying its clinical trial program for FLT180a for Hemophilia B. FLT180a is the company’s adeno-associated virus (AAV) vector-mediated gene therapy.

The primary change is the company’s plans to run dose confirmation in the Phase I/II trial instead of during the Phase IIb portion of the earlier announced Phase IIb/III pivotal trial. The company believes this modified clinical development plan will let it meet its objectives of launching the clinical trial sites for the dose confirmation portion by the end of 2021, while working to meet the FDA’s Chemistry, Manufacturing and Control (CMC) requirements in parallel while working on the Phase III trial.

If everything goes according to plan, they will have a data readout for the Phase I/II dose confirmation trial by the end of 2022 and begin the Phase III trial in the middle of 2023 and file a Biologic License Application (BLA) with the FDA by the end of 2024.

“We believe conducting dose confirmation in a Phase I/II trial should allow us to achieve similar objectives as our previously planned trial, whilst also enabling us to work with FDA on CMC prior to initiating the Phase III pivotal trial,” said Theresa Heggie, Freeline’s chief executive officer. “We are still targeting the filing of our FLT180a BLA in 2024 and are committed to bringing a functional cure to Hemophilia B patients as soon as possible. To streamline the development path of our subsequent programs, we have developed our entire pipeline from Phase I onward using the same commercial-scale manufacturing platform that we are now using for FLT180a.”

On December 14, 2020, the company reported updated data from the Phase I/II B-AMAZE trial of FLT180a in severe hemophilia B. The trial demonstrated durable Factor IX activity for a period of almost three years, with no bleeds reported that required Factor IX supplementation.

Hemophilia is a genetic bleeding disorder when the body is missing a protein that helps blood clot. In hemophilia A, there is a deficiency of clotting factor VIII protein and in hemophilia B, a deficiency of clotting factor IX protein. Hemophilia primarily affects boys and men. Women can be carriers of the affected gene and may also experience symptoms. Hemophilia A is the most common form of hemophilia, affecting about one in every 5,000 males; hemophilia B is much rarer, affecting about one in every 30,000 males. The disease is classified as mild, moderate or severe based on the level of clotting factor VIII or IX in the blood.

FLT180a (verbrinacogene setparvovec) is the gene therapy for severe hemophilia B.

The company also presented two e-posters last week at the 2021 Virtual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) on FLT180a and the Hemophilia B program, as well as presented data on the programs for Gaucher and Fabry diseases.

In December, Julie Krop, Freeline’s chief medical officer, said, “The goal of the B-AMAZE study was to evaluate a number of FLT180a doses, along with different prophylactic immune management regimens, in order to determine the optimal combination for our pivotal study to delivery predictable, consistent and durable FIX activity in the normal range. We believe delivering consistent and durable FIX activity in the normal range has the potential to allow patients to liver their life free of both the physical and psychological burdens of hemophilia B.”

Freeline also has FLT190 in Phase I/II trials for Fabry disease, FLT200 and 201 for Gaucher disease, in preclinical studies, and FLT210 in IND-enabling preclinical studies for Hemophilia A.

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