Hemophilia A Cell Therapy Stalls; Sigilon to Shift Focus to MPS and Diabetes Programs

The reprioritization comes as the SIG-001 program remains on clinical hold after scarred and inviable cell spheres were observed in a treated patient.

Sigilon Therapeutics is shifting focus from SIG-001, their hemophilia A cell therapy program currently in phase 1/2 studies (NCT04541628), to their mucopolysaccharidosis type 1 (MPS) and type 1 diabetes programs.1

“There have been key learnings in our phase 1/2 trial of SIG-001 for hemophilia A. While we continue to investigate the findings from our SIG-001 study to help inform our development of the platform, following a review of our programs, we have made the strategic decision to refocus our pipeline. We will be prioritizing MPS-1—a rare lysosomal disease—with our product candidate that is designed to produce the same enzyme as the native human structure, and Type 1 diabetes, alongside our partner, Eli Lilly, with a program that utilizes iPSC-derived islets,” Rogerio Vivaldi, president and chief executive officer, Sigilon, said in a statement.1 

The company announced the reprioritization to SIG-005, theircell therapy program in MPSand SIG-002, theircell therapy program in type 1 diabetes being developed in partnership with Eli Lilly, both of which are in investigational drug application-enabling studies, in a recent statement. Sigilon also announced a workforce reduction of around 38% to accompany the reprioritization, mainly from research, manufacturing, general, and administrative service roles.1

“We believe that prioritizing our MPS-1 and diabetes programs puts Sigilon in the best position for success,” Vivaldi added.1 “I want to thank our valued employees who will be departing Sigilon for their important contributions to the Company.”

WATCH NOW: Addressing Unmet Needs in Hemophilia: Guy Young, MD

The phase 1/2 study of SIG-001, an encapsulated cell therapy, was placed on clinical hold by the FDA in July 2021 after a serious adverse event(AE).2,3The cells in the therapy are encapsulated to protect them from the immune system and prevent scar tissue from forming around them. The patient that received the highest dose of the 3 treated patients so far developed antibodies that inhibit factor VIII, a well-known complication of factor VIII infusions. Enrollment in the study has been halted.

Further complications arose in the SIG-001 program in December 2021 when scarred, fibrosed spheres were observed during a laparoscopic retrieval procedure in a treated patient.2 The cells within the fibrosed spheres were found to be no longer viable. The 3 patients that have been dosed in the trial will continue to be followed, although future dosing in the trial remains uncertain amid the clinical hold and reprioritization.

“Patients’ safety and welfare are our highest priority. We are gathering information in order to understand these observations,” Vivaldi said in an earlier statement.2 “We will be working closely with the FDA, other regulators, and advisors to determine the impact of these observations on our programs.”

REFERENCES
1. Sigilon Therapeutics announces strategic reprioritization. News release. Sigilon Therapeutics. December 13, 2021. https://ir.sigilon.com/news-releases/news-release-details/sigilon-therapeutics-announces-strategic-reprioritization
2. Sigilon Therapeutics Announces Update on SIG-001 Phase 1/2 Study in Hemophilia A. News release. Sigilon Therapeutics. November 29, 2021. https://www.biospace.com/article/releases/sigilon-therapeutics-announces-update-on-sig-001-phase-1-2-study-in-hemophilia-a/?s=68
3. Sigilon Therapeutics announces clinical hold on Sig-001 phase 1/2 study in hemophilia A. News release. Sigilon Therapeutics. July 9, 2021. https://ir.sigilon.com/news-releases/news-release-details/sigilon-therapeutics-announces-clinical-hold-sig-001-phase-12