First successful gene therapy for haemophilia A

In a 19-month trial, haemophilia A patients were seen to have an improved level of protein FVIII when they received a single infusion of an investigational gene therapy. 11 out of 13 of those patients resulted in normal or near-normal FVIII levels. This shows promise for patients with haemophilia A as this investigational gene therapy is being hailed as the first successful one of its kind.

A viral vector is used to transfer a functional copy of the gene responsible for the production of FVIII (which is mutated in haemophilia A patients) into the patient.

The trial ensured data were recorded on 2 different dosing levels: After several weeks, all patients began producing FVIII.

From the official press release of ASH 2017:

Achievement of Normal Circulating Factor VIII Activity Following BMN 270 AAV5-FVIII Gene Transfer: Interim, Long-Term Efficacy and Safety Results from a Phase 1/2 Study in Patients with Severe Haemophilia A

By 20 weeks after the infusion, median FVIII levels in those receiving the higher dose plateaued and remained within the normal range. Those receiving the lower dose had FVIII levels that increased steadily to a median of 34 IU/dL by 20 weeks and, in the three patients who had been followed for 32 weeks, a median of 51 IU/dL — a level that is within the normal range and represents a dramatic increase over their pre-treatment FVIII levels of less than 1 IU/dL.

In contrast to standard care, which requires multiple intravenous therapy infusions per week, this gene therapy appears to have long-lasting effects after a single infusion.

Prior to this study, participants received up to 185 FVIII infusions per year to prevent bleeds, resulting in up to 41 breakthrough bleeding episodes per year despite prophylactic treatment. After receiving the gene therapy, all patients from both dose cohorts were able to completely discontinue prophylactic FVIII infusions, and 10 had no bleeding episodes requiring FVIII treatment from four weeks after infusion through the last follow-up visit. No patients showed evidence of an adverse response by the immune system, a side effect that has posed concern in trials for other gene therapies.

While several gene therapies have shown success for the rarer form, haemophilia B, gene therapy for haemophilia A has been considered more challenging because it is associated with a complex and much larger gene, making successful gene therapy considerably more difficult.

 

 

The clinical data to date for this investigational gene therapy exceeded our expectations, in terms of increasing factor VIII levels and reducing the annualized bleed rate. Many clinical trial participants have seen factor VIII levels at or close to normal. This clinical result has the potential to improve the lives of patients who now must infuse themselves with factor VIII as often as every other day. With this experimental treatment, we are researching whether it may be possible for haemophilia A patients to reduce or eliminate factor VIII treatment over an extended timeline.

lead researcher K. John Pasi, MD, professor of haemostasis and thrombosis at Barts and the London School of Medicine and Dentistry and haemophilia clinical director at Barts Health NHS Trust.