Hem A Patient in SIG-001 Trial Had Scarring in Delivery Spheres

Marisa Wexler MS avatar

by Marisa Wexler MS |

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In the first clinical trial of the experimental therapy SIG-001 for hemophilia A, one patient developed scarring in the spheres used to deliver the therapy that rendered the treatment ineffective, its developer, Sigilon Therapeutics, announced.

The Phase 1/2 trial was put on hold by the U.S. Food and Drug Administration (FDA) in July after the agency was informed by Sigilon of safety concerns in a treated patient.

“Patients’ safety and welfare are our highest priority. We are gathering information in order to understand these observations,” Rogerio Vivaldi, MD, Sigilon’s president and CEO, said in a press release.

In hemophilia A, mutations lead to insufficient activity of a clotting protein called factor VIII (FVIII). SIG-001 is composed of human cells that are engineered to produce FVIII. These cells are embedded in a dual-layer sphere made up of Sigilon’s proprietary Afibromer artificial biomaterials matrix, which is designed to allow cells to have access to nutrients while they release FVIII into the body.

Sigilon is sponsoring the Phase 1/2 trial (NCT04541628) to test the safety, tolerability, and early efficacy of SIG-001 in adults with severe or moderately severe hemophilia A.

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One of the three patients dosed with SIG-001, however, developed inhibitors — antibodies made by the immune system that bind to FVIII and block its activity.

At the direction of the study investigator, that patient underwent a surgical procedure to retrieve the SIG-001 spheres. Upon inspection, it was determined that the spheres had fibrosed, or scarred, and that cells within them were no longer viable.

According to Sigilon, the three enrolled patients will continue to be followed according to the study’s protocol. In the meantime, the fibrosed spheres will be investigated.

“We will be working closely with the FDA, other regulators, and advisors to determine the impact of these observations on our programs,” Vivaldi said.

The safety review committee for the SIG-001 trial is meeting in December and will discuss these findings, as well as the FDA’s clinical hold. According to Sigilon, it is possible that these findings will affect plans for a Phase 1/2 trial testing SIG-005, a cell-based experimental therapy that the company is developing to treat mucopolysaccharidosis type I, a rare lysosomal storage disorder.