Jul 12, 2021

The U.S. Food and Drug Administration (FDA) has placed a clinical hold on Sigilon Therapeutics’ phase 1/2 study of SIG-001 in patients with severe or moderately severe hemophilia A.

SIG-001 is a cell-based therapy, designed to carry significant amounts of synthetic DNA material that can prompt the production of the therapeutic protein factor VIII (FVIII). The therapy includes a “shield” composed of a synthetic biomaterial called Afibromer™ which is designed to effectively block unwanted immune responses such as cell-to-cell interaction with the patient immune system and prevention of fibrosis to biomaterials - in this instance an inhibitor response was actually the impetus for the clinical hold. It was initiated once Sigilon submitted a report of a serious adverse event (SAE) and temporary enrollment halt to the FDA and other regulatory agencies.

Of the three patients who have thus far have been dosed with SIG-001 in the phase 1/2 trial, the one who received the highest dose developed inhibitors to FVIII. According to a Sigilon news release, the patient is responding well to medical treatment, as his “condition continues to improve.” The FDA has requested additional information and data that could help identify potential contributors to the inhibitor response, including family history and immune stimulation from a recent vaccination. All three patients enrolled in the trial will continue to be followed per study protocol, as the company continues to investigate the SAE. 

“Patient safety is our top priority, and we are encouraged that the patient is recovering,” said Rogerio Vivaldi, MD, 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.”

As has been our past practice (and consistent with the principles articulated at the January 2020 Safety Summit), HFA and NHF commit to keeping the bleeding disorders community informed as we gather further information. Community members are encouraged to submit your questions and concerns to our joint Safety Inbox here.

Source: Sigilon Therapeutics news release dated July 9, 2021

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