FDA Places Clinical Hold on Sigilon’s Phase 1/2 Study in Hemophilia A

U.S. Food and Drug Administration has placed a hold on Sigilon Therapeutics’ phase 1/2 study of SIG-001 in patients with severe or moderately severe hemophilia A after the company reported a serious adverse event and temporarily halted enrollment in the trial.

Photo: Rogerio Vivaldi, president and CEO of Sigilon

Hemophilia A, also called Factor VIII deficiency or classic hemophilia, is an X-linked genetic disorder caused by missing or defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a new mutation that was not inherited. Approximately 1 in 10,000 people have Hemophilia A.

People living with hemophilia A lack sufficient functioning Factor VIII protein to help their blood clot and are at risk for painful and/or potentially life-threatening bleeds from even modest injuries. Additionally, people with the most severe form of hemophilia A, approximately half of sufferer, often experience painful, spontaneous bleeds into their muscles or joints.

The standard of care for individuals with severe hemophilia A is a prophylactic regimen of replacement Factor VIII infusions administered intravenously up to two to three times per week or 100 to 150 infusions per year. Despite these regimens, many people continue to experience breakthrough bleeds, resulting in progressive and debilitating joint damage, which can have a major impact on their quality of life.

Sigilon’s SIG-001 is a non-viral engineered cell-based therapy designed to produce Factor VIII and be a functional cure for hemophilia A. The engineered cells are protected by a proprietary biomaterials matrix, which shields them from immune rejection and fibrosis.

Sigilon said that to date, three patients have been dosed with SIG-001. The third patient, who received the highest dose of study drug, developed inhibitors to Factor VIII—a well-known complication of FVIII therapy. The patient is responding well to medical treatment and his condition continues to improve.

Among other things, the FDA has requested additional information or data on factors potentially contributing to the development of inhibitors in this patient, such as family history and immune stimulation from a recent vaccination. All three patients enrolled in this study will continue to be followed per study protocol, while the company investigates the serious adverse event (SAE). 

“Patient safety is our top priority, and we are encouraged that the patient is recovering,” said Rogerio Vivaldi, president and CEO of Sigilon. “In collaboration with the regulatory agencies and our advisors, we are conducting a thorough investigation of this event to confirm whether there was a causal relationship between the development of inhibitors and SIG-001. We are committed to working with the FDA to resolve the clinical hold.”

Sigilon said the status of the SAE investigation will continue to be reviewed by the Safety Review Committee for SIG-001 and the company will provide additional data when available.

Author: Rare Daily Staff