Freeline Moves Closer to Identifying Hemophilia B Gene Therapy Dose


A second cohort has been dosed with 7.7e11 vg/kg to hopefully confirm the dose for phase 3 trials.

The gene therapy FLT180a (Freeline Therapeutics) restored factor IX (FIX) production in patients with hemophilia B, according to new data from the phase 1/2 B-LIEVE trial (NCT05164471).1

These data were presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress, July 9-13, in London, UK, by Guy Young, MD, director, Hemostasis and Thrombosis Program, Children’s Hospital of Los Angeles and professor of Pediatrics, Keck School of Medicine, University of Southern California.

“The initial data show that FLT180a provides rapid and consistent elevations in FIX to normal levels, which can prevent bleeding and the need for regular FIX replacement in people with hemophilia B,” Pamela Foulds, MD, chief medical officer, Freeline, said in a statement.2 “Emerging data suggest that while FIX expression was maintained at protective levels, a further refined immune management regimen may be required to avoid mild and transient transaminitis and to sustain FIX levels in the normal range. Potential adjustments in cohort two and forthcoming results from that cohort will help us interpret this further.”

Data from the 3 patients in cohort 1 treated with FLT180a were presented demonstrating a rapid increase of FIX to normal levels of 93, 92 and 80 IU/dL through days 77, 56 and 36, respectively, as of the data cut-off of May 23, 2022. 1Patients were all treated with 7.7e11 vg/kg and all stopped and did not have to resume FIX prophylaxis after treatment.

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Overall, the adeno-associated virus vector S3 gene therapy and the prophylactic immune management regimen were well-tolerated. No serious adverse events (AEs) were observed, with most being mild and transient. These AEs were related to immune management and were consistent with the known profiles of corticosteroids and tacrolimus. No infusion reactions were observed, and there has been no evidence of FIX inhibitors.

Two patients have experienced a decrease in FIX expression along with a mild, transient increase in liver enzymes, although all patients’ levels have remained elevated above baseline and no patients have experienced bleeds or needed FIX therapy. Cohort 2 recently completed dosing in June 2022 and data so far seem similar to that of cohort 1. These patients received the same dose of FLT180a and prophylactic immune management regimen that were used in the first cohort based off data from the cohort and advice from the independent Data Monitoring Committee and Freeline hopes to confirm the dose for phase 3 trials.

“Our strategy is to advance gene therapy programs that have the potential to deliver best-in-class or first-in-class treatments,” Michael Parini, chief executive officer, Freeline added to the statement.2 “While we continue to believe FLT180a has the potential to deliver a best-in-class gene therapy for people with hemophilia B, the availability of other treatment options and the need to prioritize our valuable resources dictate that we evaluate strategic options for FLT180a. These include, but are not limited to, seeking a partner that would enable the continuation of FLT180a through Phase 3 development.”

1. Young G, Chowdary P, Barton S, Yee D, Flight P, Ferrante F. Results from B-LIEVE, a Phase 1/2 Dose-Confirmation Study of FLT180a AAV Gene Therapy in Patients with Hemophilia B. Presented at: 2022 ISTH Congress, July 9-13, London, UK.
2. Positive initial clinical data from the B-LIEVE dose-confirmation trial for FLT180a in hemophilia B presented at the International Society on Thrombosis and Haemostasis Congress. July 10, 2022.
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