2nd Hem B Patient Group Begins Dosing in Gene Therapy Trial
Dosing has begun in a second group of hemophilia B patients enrolled in a Phase 1/2 dose-confirmation trial of the experimental gene therapy FLT180a, the treatment’s developer, Freeline, announced.
The dose determined to be optimal in this study is expected to finalize plans for a pivotal Phase 3 trial that could be launched next year.
“Our goal is to provide transformative and durable one-time treatments to people with severe chronic diseases. We are working with urgency to advance our therapeutic candidates … FLT180a is on track to deliver proof of concept that our gene therapies have the potential to achieve our goal,” Michael Parini, Freeline’s CEO, said in a press release.
Hemophilia B is caused by mutations in the gene that codes for a clotting protein called factor IX or FIX. The gene therapy FLT180a uses a viral vector to deliver a healthy version of this gene to the body’s cells, ultimately aiming to restore production of functional FIX and prevent excessive bleeding.
“The ultimate promise of gene therapy is a functional cure,” said Pamela Foulds, MD, chief medical officer of Freeline.
The Phase 1/2 B-LIEVE trial (NCT05164471) is evaluating FLT180a in up to nine men with severe or moderately severe hemophilia B, meaning FIX activity levels of 2% or lower.
The trial launched earlier this year at a single site in California, with the first patient dosed in March. The study’s first cohort or patient group included three men, each given a single infusion of FLT180a at a dose of 7.7e11 vector genomes per kilogram (vg/kg). Participants also received a prophylactic (preventive) immune-suppressing treatment regimen to prevent an immune response against the therapy, which could cause side effects or lower the therapy’s effectiveness.
Based on the advice of an Independent Data Monitoring Committee — a group of outside experts tasked with ensuring participants’ safety in the study — dosing in the second cohort is starting. These patients will be treated with FLT180a at the same dose and with the same prophylactic regimen as was used in the first cohort.
According to Freeline, treatment findings in from first patient group will be presented next month at the International Society on Thrombosis and Haemostasis (ISTH) Congress in London.
“The initial data from the first B-LIEVE cohort enhance our confidence that a low, one-time dose of FLT180a with a short, prophylactic immune management regimen has the potential to provide a functional cure to people with hemophilia B by delivering predictable and sustained FIX normalization together with a good safety profile, ” Foulds said.
“The data also provide confidence in the dosing for our pivotal Phase 3 trial, which we anticipate beginning in 2023 as planned,” she added.
Patients in a previous Phase 1/2 trial called B-AMAZE (NCT03369444) are being followed to assess the gene therapy’s long-term safety and effectiveness in an ongoing study (NCT03641703) expected to run through December 2035. The company announced last year that factor IX levels within the normal range had been achieved with relatively low doses of FLT180a and maintained for more than three years.
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