Long-term data published on Freeline’s Hemophilia B gene therapy candidate

Novel data from Freeline Therapeutics’ (Stevenage, UK) B-AMAZE Phase I/II dose-finding trial of their liver-directed adeno-associated virus (AAV) gene therapy candidate, FLT180a, for people with hemophilia B has been published in the New England Journal of Medicine.

Hemophilia B is a rare blood clotting disorder caused by a mutation in the gene F9, which encodes coagulation factor IX on the X chromosome. The mutation results in a deficiency in factor IX. Depending on the levels of factor IX in the blood, hemophilia B is classified as mild, moderate, or severe. Current disease management strategies are limited to lifelong replacement therapy with recombinant factor IX.

Gene therapy, therefore, represents a promising potential solution to address the underlying causes of hemophilia B and alleviate reliance on factor IX replacement therapy. FLT180a is a gene therapy candidate utilizing an adeno-associated virus capsid to target the delivery of a codon-optimized F9 gene with a gain-of-function mutation to liver cells. It is currently being evaluated in Phase I/II clinical trials in adults with severe or moderately severe hemophilia B.

The B-AMAZE Phase I/II multicenter, open-label, single-dose study aimed to assess the safety and efficacy of varying doses of FLT180a. Patients received one of four doses of FLT180a alongside an immunosuppressant to decrease the risk of vector-related immune responses. Patients treated in B-AMAZE are being observed in a long-term follow-up study.

In the data from B-AMAZE published recently in the New England Journal of Medicine, all ten patients had dose-dependent increases in levels of factor IX following FLT180a treatment. At the median follow-up of 27.2 months post-dosing, nine of the ten patients had sustained factor IX activity. At the data cut-off date of 20 September 2021, five patients showed normal blood levels of factor IX (51–78%), three patients had levels from 23% to 43%, and one high-dose patient had a level of 260%.

Additionally, the mean annualized bleeding rate across all patients decreased from 2.93 events/year at baseline to 0.71 events/year after treatment with FLT180a. The mean annualized factor IX consumption per patient decreased from 226,026 IU/year to 9,723 IU/year.

While the treatment was generally well tolerated, adverse events (AEs) were reported in all patients. The most common FLT180a-related AE was transient transaminitis and the immunosuppressant-related AEs were consistent with the established safety profiles of the drugs used. In addition, a serious AE of arteriovenous fistula thrombosis occurred in the patient with high factor IX levels.

A Phase I/II dose-confirmation trial of FLT180a, B-LIEVE, is in progress to finalize a dose for a Phase III pivotal trial.

Amit Nathwani, co-founder and board member of Freeline, stated, “The B-AMAZE long-term data add to the growing body of evidence that gene therapy has the potential to free patients from the challenges of having to adhere to lifelong therapy or could provide treatment where none exists today.”

Michael Parini, CEO of Freeline, commented, “In addition to the promise FLT180a holds for people with hemophilia B, these long-term data demonstrate the potential of our proprietary AAVS3 capsid to enable strong and durable gene expression at low vector doses to effectively treat debilitating inherited diseases with a good safety profile.”

 

Source: https://www.globenewswire.com/en/news-release/2022/07/21/2483488/0/en/New-England-Journal-of-Medicine-Publishes-Positive-Long-Term-Data-on-Freeline-s-Gene-Therapy-Candidate-FLT180a-for-People-with-Hemophilia-B.html