Vertex Pauses Diabetes Cell Therapy Trial After Unrelated Patient Deaths

Vertex Pharmaceuticals has placed its diabetes type 1 cell therapy program on a protocol-specified pause following 2 patient deaths that occurred in the phase 1/2 clinical trial (NCT04786262). Vertex has stated that the deaths were unrelated to VX-880 therapy.¹

VX-880 is an allogeneic, stem cell-derived, fully differentiated, insulin-producing islet cell therapy designed to be used in conjunction with standard immunosuppression to reduce recurrent hypoglycemia events. The company also shared updates on the program, including the completion of enrollment in the trial. All 14 patients have demonstrated islet cell engraftment and endogenous insulin production. All patients in parts A and B have demonstrated glycemic control to target ADA recommended levels with HbA1C <7% except 1 patient who withdrew consent from the study. Apart from the reported deaths, the safety profile has been consistent with immunosuppressives, the perioperative period and past medical history.

The latest full data update on VX-880 was presented at the Annual Meeting of The European Association for the Study of Diabetes (EASD), held October 2-6 in Hamburg, Germany, by Professor Trevor Reichman, MD, transplant surgery, Toronto General Hospital, Canada.2Out of the 6 participants from which data were presented, 2 with over a year of follow-up met the primary endpoint of eliminating severe hypoglycemic events as well as a secondary endpoint of insulin independence. No serious adverse events were related to VX-880 therapy; 2 transient transaminase elevations were related and resolved.

“These results are truly remarkable and offer hope of a life-changing therapy for people who suffer from the relentless life-long burden of T1D”, Reichman said in a statement.³ “All patients who have been treated with VX-880 have shown improvement across all measures of glucose control, including reduction or even elimination of external insulin use.”

READ MORE: CGTLive's Pillars of Progress 2023: Top News in Endocrinology

The VX-880 trial was previously placed on hold by the FDA in May 2022, after the FDA determined there was insufficient information to support dose escalation, despite an Independent Data Monitoring Committee’s recommendation to advance patients to part B of the study and full dosing. The FDA later lifted the hold in July 2022.⁴

The news puts a bit of a damper on Vertex’s 2024, as opposed with its groundbreaking 2023 approval of exagamglogene autotemcel (exa-cel) for sickle cell disease (SCD) treatment, the first approved gene editing therapy developed in collaboration with CRISPR Therapeutics.⁵ The therapy, marketed as Casgevy, was approved in patients aged 12 years and older with SCD with recurrent vaso-occlusive crises.

“We continue to reach more patients than ever before with our CF medicines; we’ve launched CASGEVY™ in the U.S., UK and Bahrain following the historic approvals of this gene editing therapy late last year, and we are well positioned to advance our mission of bringing additional transformative medicines to people with serious diseases,” Reshma Kewalramani, MD, chief executive officer and president, Vertex, said in a statement.¹

REFERENCES

1. Vertex provides pipeline and business updates in advance of upcoming investor meetings. News release. January 7, 2024. https://www.businesswire.com/news/home/20240107188174/en/Vertex-Provides-Pipeline-and-Business-Updates-in-Advance-of-Upcoming-Investor-Meetings
2. Reichman TW, Ricordi C, Naji A, et al. Glucose-dependent insulin production and insulin independence in type 1 diabetes from stem cell-derived, fully differentiated islet cells: Updated data from the VX-880 clinical study. Presented at: EASD Annual Meeting, October 2-6, 2023.
3. New stem cell-derived islet therapy improves blood sugar control in all treated patients, with three achieving insulin independence. News release. Vertex Pharmaceuticals.
4. Vertex announces FDA has lifted the clinical hold on VX-880 phase 1/2 clinical trial for the treatment of type 1 diabetes. News release. Vertex Pharmaceuticals. July 5, 2022. https://www.businesswire.com/news/home/20220705005299/en/Vertex-Announces-FDA-Has-Lifted-the-Clinical-Hold-on-VX-880-Phase-12-Clinical-Trial-for-the-Treatment-of-Type-1-Diabetes
5. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. News release. FDA. December 7, 2023. Accessed December 7, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease