Hemophilia A Gene Therapy Candidate SB-525 Posts Good Early Trial Results

The investigational gene therapy SB-525 is tolerated well by patients, and dose-dependent responses are positive, according to preliminary results of a Phase 1/2 clinical trial of hemophilia A.

The potential gene therapy is being developed as a partnership between Sangamo Therapeutics and Pfizer. It consists of fragments of genetic material containing the information to produce factor VIII, the protein missing in hemophilia A.

SB-525 treatment hopes to reduce or even eliminate patients’ need for factor VIII replacement therapy by inducing cells to produce its own protein.

2017 was particularly eventful in the clinical development of SB-525 therapy. In May, the two companies announced a collaboration to develop the gene therapy product to treat hemophilia A, and the U.S. Food and Drug Administration (FDA) granted it fast track designation days later.

The European Medicines Agency (EMA) also gave the investigational therapy orphan medicinal product status for hemophilia A in Europe.

Sangamo began the Phase 1/2 Alta study (NCT03061201) to investigate the safety, tolerability and time-course profile of factor VIII levels in hemophilia A patients infused with escalating doses of SB-525.

Two outcomes of the treatment are being evaluated as primary goals in the study — the number of treatment-related adverse events, and changes in circulation levels of factor VIII. Both will be monitored up to three years. The trial is still recruiting male participants.

Preliminary data from the Alta trial show that, to date, five patients were treated at three dose levels and a sixth patient will start the treatment later this month. The study enrolls two patients per dose group, in this initial dose-escalation phase.

So far, SB-525 has been generally well-tolerated with no observed treatment-related serious adverse side effects. There also was no need for tapering courses (reducing doses) of oral steroids.

The fifth participant, the first at the highest dose level, was treated in June and achieved therapeutic levels of factor VIII activity, meaning an increase of at least 12 percent in factor VIII activity, the level associated with substantial reduction or elimination of spontaneous bleeding and factor usage.

Importantly, researchers found a dose-dependent response in participants, with patients in the second dose group reporting reduced use of factor replacement therapy.

“We have made good progress with dose escalation in this study and are encouraged by the safety and tolerability profile to date and by the attainment of therapeutic factor VIII activity levels in the first patient in the third dose cohort,” Edward Conner, MD, chief medical officer of Sangamo, said in a press release.

“We look forward to generating additional data to assess the consistency and sustainability of the factor VIII expression observed,” Conner said.

Detailed data from the Alta study is expected to be presented at a hematology conference later this year.