Nov 29, 2021

Sigilon Therapeutics today reported a new development in the company’s phase 1/2 clinical study of SIG-001 in individuals with severe or moderately severe hemophilia. This follows the events of this past summer when the U.S. Food and Drug Administration (FDA) placed a clinical hold on the trial due to an unwanted inhibitor response in one of the three patients participating in the study. In a new press release, Sigilon stated that “fibrosed spheres” were observed during a retrieval procedure in this same patient.

These encapsulating spheres represent a key component of SIG-001, a cell-based therapy developed to carry significant amounts of synthetic DNA material that can illicit production of the therapeutic protein factor VIII. They are composed of a shielding outer layer made up of a synthetic biomaterial called Afibromer™ designed to block unwanted immune responses such as cell-to-cell interaction with the patient’s immune system and to prevent fibrosis (formation of excessive fibrous tissue) to biomaterials.

According to the Sigilon release, the patient underwent a laparoscopic procedure prescribed by the investigator to retrieve the implanted spheres. An examination of the spheres showed them to be fibrosed and the cells within to be “no longer viable.”

The company has signaled that it will continue to investigate the fibrosed spheres in this patient and to monitor all three trial participants as per study protocol. In the meantime, the FDA’s clinical hold remains in place pending a review by the Safety and Review Committee for SIG-001 this December.

“Patients’ safety and welfare are our highest priority. We are gathering information in order to understand these observations,” said Rogerio Vivaldi, MD, President and CEO of Sigilon. “We will be working closely with the FDA, other regulators, and advisors to determine the impact of these observations on our programs.”

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 press release dated November 29, 2021