First Patient Dosed in Pivotal AFFINE Study of Potential Gene Therapy SB-525

David Melamed, PhD avatar

by David Melamed, PhD |

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The first participant was dosed with the investigational gene therapy treatment SB-525 (giroctocogene fitelparvovec) in a Phase 3 clinical trial in men with hemophilia A, according to developers Pfizer and Sangamo Therapeutics.

AFFINE (NCT04370054) is a pivotal trial, which means it is intended to provide enough data to support regulatory approval of SB-525. Trial participants must have completed a minimum of six months of routine prophylaxis (preventive) therapy during the lead-in Phase 3 study (NCT03587116), designed to collect data for efficacy and safety parameters. Enrollment in the lead-in study is ongoing at multiple locations in the U.S. and internationally.

“The initiation of the pivotal Phase 3 dosing study of giroctocogene fitelparvovec [SB-525] is a significant achievement for Pfizer as we continue our longstanding commitment to improving care for the hemophilia community,” Brenda Cooperstone, chief development officer of rare disease at Pfizer Global Product Development, said in a press release.

Originally developed by Sangamo, SB-525 is an experimental gene therapy that uses an adeno-associated viral vector (AAV6) to deliver genetic material to liver cells to enable production of  FVIII protein – the blood clotting factor that is missing or defective in people with hemophilia A — and eliminate the need for a lifetime of replacement therapies.

The AAV6 vector is engineered to be harmless to humans, and also to have a specific affinity for liver cells.

SB-525 is meant to be a one-time treatment, administered directly into the bloodstream. The therapy was granted fast track, orphan drug, and regenerative medicine advanced therapy (RMAT) designations by the U.S. Food and Drug Administration, as well as an orphan medicinal product designation from the European Medicines Agency.

Results of an ongoing Phase 1/2 trial, called Alta (NCT03061201, also still recruiting), showed that treatment over 14 months with the highest dose of SB-525 — 3×1013 vector genomes (vg)/kg body weight — led to sustained elevation in FVIII levels in five patients, with no bleeding episodes or use of replacement therapies.

Data presented recently also showed that those benefits were sustained at 85 weeks of treatment, with FVIII activity reaching a clinically meaningful level.

“We are encouraged that findings from the Phase 1/2 Alta study met two critically important measures for the hemophilia A patient community, showing clinically meaningful factor levels and reduced bleeds,” said Bettina Cockroft, MD, chief medical officer of Sangamo. “The progress of this program, the most advanced of our gene therapy product candidates, into Phase 3 is an important milestone for Sangamo, as it represents our first asset in a registrational trial,” she said.

The Phase 3 AFFINE trial will include more than 60 men with moderately severe to severe hemophilia A, ages 18 to 64.

Patients will be monitored for five years to determine long-term safety and effectiveness data. The primary goal of AFFINE is to assess the annual bleed rate one year after treatment compared to results with replacement therapy in the lead-in period. The secondary goal of the trial is to monitor FVIII protein activity levels both initially after treatment (once a steady state has been reached), and again at one year.

“Given the Phase 1/2 study findings to date, we believe that giroctocogene fitelparvovec has the potential to sustain factor levels and reduce annual bleed rates, suggesting this one-time gene therapy could potentially transform the standard of care for eligible patients worldwide,” Cooperstone added.