SB-525 Gene Therapy Phase 1/2 Trial Begins for Hemophilia A Patients

The first patient in a Phase 1/2 clinical trial (“the Alta trial”) designed to assess safety and tolerability of SB-525 gene therapy has received treatment. Sangamo Therapeutics, in a collaboration with Pfizer, is developing  the SB-525 gene therapy to correct the Factor VIII (FVIII) defect in hemophilia A patients.

The Alta trial (NCT03061201) is currently recruiting up to 20 male patients with severe hemophilia A, as evidenced by a circulating FVIII activity that is less than 1% of normal. This dose-ranging study, taking place in Seattle and Duarte, California, will assess SB-525 adverse events and the levels of circulating FVIII for up to three years after a single SB-525 infusion.

Hemophilia A patients need to repeatedly receive FVIII blood infusions to replace defects in blood clotting Factor VIII and prevent bleeding. Now, a single SB-525 administration may enable patient’s own cells to constantly produce the same amino acid sequence used in replacement therapy (Refacto and Xyntha).

SB-525 relies on a genetically engineered virus, recombinant adeno-associated virus (rAAV), carrying a “healthy” FVIII gene construct. The rAAV is harmless for humans, and it delivers the corrected gene to cells in tissues. SB-525 rAAV is designed to restrict FVIII gene expression to the liver, a strategy intended to increase FVIII long-term hepatic production in hemophilia A patients.

This potential therapy results from a global collaboration and license agreement between Sangamo and Pfizer to develop and commercialize gene therapies for hemophilia. “We are excited to see progress in our partnership program for SB-525 with Sangamo,” said Greg LaRosa, chief scientific officer, Pfizer Rare Disease, in a press release issued by Sangamo. “[W]e are advancing the promise of gene therapy with the hope of making a meaningful impact for people living with Hemophilia A.”

Earlier this year, the U.S. Food and Drug Administration granted Orphan Drug and Fast Track designations to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency.

Sangamo is also conducting a Phase 1 trial (NCT02695160) of a gene therapy, SB-FIX, in males with severe hemophilia B. This study is currently recruiting up to 12 patients at sites in California and Michigan, and more information is available on its clinical trials.gov webpage.