Vertex Pharmaceuticals has reported breakthrough results from its ongoing Phase I/II clinical trial of VX-880, an investigational stem cell-derived islet cell therapy for type 1 diabetes (T1D). The data, presented at the American Diabetes Association's 84th Scientific Sessions, demonstrated that patients achieved insulin independence and complete elimination of severe hypoglycemic events, marking a potential paradigm shift in T1D treatment.
Trial Design and Patient Population
The FORWARD study is a multicentre, open-label, single-arm Phase I/II trial designed to evaluate the safety and efficacy of VX-880 in adults with T1D who experience impaired hypoglycemic awareness and severe hypoglycemic events (SHEs). The study enrolled patients with particularly challenging disease management, including those with at least two SHEs in the year before screening.
At baseline, all 14 dosed patients had undetectable fasting C-peptide levels, indicating complete loss of endogenous insulin production. Participants had an average age of approximately 44 years, mean HbA1c of 7.8%, and total daily insulin use of approximately 40 units per day. Patients had experienced between two and four SHEs in the year prior to screening, representing a high-risk population with substantial unmet medical needs.
Remarkable Efficacy Outcomes
The results demonstrated unprecedented efficacy for VX-880 across multiple endpoints. All patients showed islet cell engraftment and glucose-responsive insulin production by day 90 post-infusion. The 12 patients who received the full dose in Parts B and C of the study all demonstrated improved glycemic control, achieving the American Diabetes Association's recommended targets for HbA1c below 7.0% and time-in-range above 70%.
Most remarkably, nearly all participants (11 out of 12) had reduced or eliminated their need for exogenous insulin at their last visit. Of the 10 participants who completed the Day 180 visit, seven are no longer using exogenous insulin, while two achieved approximately 70% reduction in their daily insulin use.
All patients experienced complete elimination of SHEs from day 90 onwards, addressing one of the most dangerous complications of T1D. Three patients who completed at least one year of follow-up met both the primary endpoint of SHE elimination with HbA1c below 7.0% and the secondary endpoint of insulin independence. Notably, 100% of patients with greater than one year of follow-up achieved these stringent criteria.
Safety Profile and Tolerability
The treatment demonstrated a favorable safety profile throughout the study period. VX-880 was well tolerated, with most adverse events being mild or moderate in nature. Importantly, no serious adverse events were linked to VX-880 administration. While two patient deaths occurred during the study period, both were deemed unrelated to the investigational treatment.
Clinical Significance and Future Development
The results represent a potential breakthrough in T1D treatment, offering hope for patients who have long relied on exogenous insulin administration. According to recent surveys, approximately 6% of individuals with T1D experience recurrent severe hypoglycemic events and have impaired awareness of hypoglycemia, conditions that can lead to confusion, coma, seizures, cardiovascular events, and even death if left untreated.
"These remarkable data add to the growing body of evidence for VX-880 as a potentially curative therapy for T1D," said Carmen Bozic, executive vice-president and chief medical officer of Vertex Global Medicines Development and Medical Affairs. "As we plan toward pivotal development, we are pleased to have secured regulatory approval to expand study enrolment and look forward to advancing this programme for patients who have long awaited a transformative therapy."
Dr. Piotr Witkowski, Professor of Surgery and Director of the Pancreatic and Islet Transplant Program at the University of Chicago, who serves as one of the study investigators, emphasized the potential impact: "This positive data adds to the growing body of evidence for VX-880's potential to revolutionize the treatment of type 1 diabetes that would give patients an alternative solution other than exogenously administered insulin."
Study Expansion and Next Steps
Based on the positive outcomes observed, Vertex has expanded the study to include approximately 37 patients total. The original study, now fully enrolled with 17 patients, has dosed 14 participants across Parts A, B and C, with the remaining participants set to receive their doses shortly. This expansion aims to generate additional clinical data that will support the goal of making VX-880 available for people living with T1D in the future.
The data indicate that VX-880 stem cell-derived islets function like natural islets and demonstrate the potential to provide profound benefit to patients with this challenging autoimmune condition. As Vertex plans toward pivotal development, these results position VX-880 as a potentially transformative therapy for patients with T1D who continue to face significant unmet medical needs despite advances in diabetes technology.
