Novel stem cell-derived therapy for type 1 diabetes shows promising results

Vertex Pharmaceuticals Incorporated has shared results of Phase 1/2 of its clinical trial in which after only 90 days of its ongoing investigational study, the patient's insulin needs were reduced from 34 daily units down to 3 daily units.

The patient was treated with a single infusion of VX-880 at half the target dose in conjunction with immunosuppressive therapy. The patient achieved successful engraftment and demonstrated rapid and robust improvements in multiple measures, including increases in fasting and stimulated C-peptide, improvements in glycemic control, including HbA1c, and decreases in exogenous insulin requirement. VX-880 was generally well tolerated.

"These results from the first patient treated with VX-880 are unprecedented. What makes these results truly remarkable is that they were achieved with treatment at half the target dose," said Bastiano Sanna, Ph.D., Executive Vice President and Chief of Cell and Genetic Therapies at Vertex. "While still early, these results support the continued progression of our VX-880 clinical studies, as well as future studies using our encapsulated islet cells, which hold the potential to be used without the need for immunosuppression."

"As a surgeon who has worked in the field of islet cell transplantation for decades, this approach, which obviates the need for an organ donor, could be a game changer," said James Markmann, M.D., Ph.D., Professor of Surgery and Chief of the Division of Transplant Surgery at Massachusetts General Hospital. "We are excited to progress this unique and potentially transformative medicine through clinical trials and to patients."

"More than a decade ago our lab had a vision for developing an islet cell replacement therapy to provide a functional cure to people suffering from T1D," said Doug Melton, Ph.D., Xander University Professor at Harvard and an Investigator of the Howard Hughes Medical Institute. "These promising results bring great hope that stem cell-derived, fully differentiated islet cells could deliver a life-changing therapy for people who suffer from the relentless life-long burden of T1D."

Efficacy Results

The patient was diagnosed with T1D approximately 40 years ago and has been dependent on exogenous insulin. In the one year prior to treatment, the patient experienced 5 severe, potentially life-threatening hypoglycemic episodes. Prior to treatment with VX-880, the patient's insulin dose was 34 units per day and fasting and stimulated C-peptide levels were undetectable, indicating that the patient was not making their own insulin. Per the study protocol, the patient received half the target dose of VX-880 through a hepatic portal vein infusion in combination with a standard regimen of immunosuppressive agents.

Fasting C-peptide, HbA1c and 7-day average daily insulin dose were measured at various intervals after VX-880 treatment through Day 90. Fasting C-peptide was detected early after treatment with VX-880 and increased rapidly to Day 90. In parallel, HbA1c and daily insulin dose decreased over time.

Islet cell function was evaluated at baseline and at Day 90 using a Mixed Meal Tolerance Test (MMTT) with quantification of C-peptide levels, a direct marker for insulin production. At baseline prior to VX-880 treatment, fasting and stimulated C-peptide levels were undetectable, indicating no endogenous insulin production. At Day 90 after VX-880 treatment, fasting C-peptide was 280 pmol/L, reflecting restored basal insulin production and increased after MMTT stimulation to a peak of 560 pmol/L, indicating that VX-880 restored glucose-responsive insulin production. Also at Day 90, HbA1c improved from 8.6% at baseline to 7.2%, and daily insulin dose decreased from 34 units per day prior to treatment with VX-880 to an average dose of 2.9 units per day over a 7-day period at the Day 90 visit, reflecting a 91% decrease in daily exogenous insulin use.

Safety Results

In this first patient, the safety of VX-880 was generally consistent with the immunosuppressive regimen used in this study. There were no serious adverse events (SAE) considered related to VX-880, and the majority of the adverse events were considered mild to moderate. The most common adverse events were severe hypoglycemic events, which were non-serious, not related to VX-880, and occurred in the perioperative period. Through Day 90, the patient had one SAE; this was a rash that was mild in severity, not related to VX-880, and the majority of the adverse events were considered mild to moderate. The most common adverse events were severe hypoglycemic events, which were non-serious, not related to VX-880, and occurred in the perioperative period. Through Day 90, the patient had one SAE; this was a rash that was mild in severity, not related to VX-880, and resolved.