The patient’s daily insulin requirement went from 34 units a day at baseline to 2.9 units a day 90 days after treatment.
VX-880 has restored insulin production in the first patient with type 1 diabetes dosed in a phase 1/2 trial (NCT04786262) of the stem cell-derived therapy, according to 90-day data announced by Vertex, who is developing the therapy.
The patient experienced a 91% decrease in their daily insulin requirement and robust improvements in glucose control as measured by HbA1c. After a Mixed Meal Tolerance Test (MMTT) at 90 days post-treatment, the patient achieved a C-peptide of 560 pmol/L.
“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, PhD, executive vice president and chief, cell and genetic therapies, Vertex, in a statement. “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.”
VX-880 is an investigational, stem cell-derived, fully differentiated pancreatic islet cell replacement therapy. It is designed to restore islet cell function to be able to regulate glucose levels and insulin production. It is infused into the hepatic portal vein and treated patients require chronic immunosuppressive therapy.
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The open-label, single-arm, multi-center trial plans to enroll 17 patients with type 1 diabetes with impaired hypoglycemic awareness and severe hypoglycemia as the first part of a multi-part trial evaluating VX-880's safety and efficacy. The first 2 patients (the first of which has been dosed) will be dosed with half the target dose. Subsequent patients will be dose-escalated to the target dose.
“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,” James Markmann, MD, PhD, professor, surgery and chief, transplant surgery, Massachusetts General Hospital, added to the statement. “We are excited to progress this unique and potentially transformative medicine through clinical trials and to patients.”
The first participant was diagnosed with type 1 diabetes around 40 years ago and has depended on exogenous insulin. In the year before treatment, the patient experienced 5 severe hypoglycemic episodes. Ninety days after treatment, the participant’s daily insulin dose decreased from 34 units per day at baseline to 2.9 units per day. The participant’s fasting C-peptide levels went from being undetectable at baseline to 280 pmol/L with peak levels of 560 pmol/L after MMTT stimulation. HbA1c also improved from 8.6% at baseline to 7.2%.
“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,” Doug Melton, PhD, Xander University Professor, Harvard and investigator, Howard Hughes Medical Institute, said in the statement. “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.”
Adverse events (AEs) in the trial were generally related to the type 1 diabetes and immunosuppressive regimen. No serious AEs were deemed related to treatment. Most AEs were mild to moderate and severe hypoglycemic events in the perioperative period were the most common AEs. A mild rash was the only serious AE and this resolved.
Vertex plans to continue the phase 1/2 program based on these positive data. Their clinical trial application has been approved in Canada and the trial is currently being conducted across multiple sites in the US. Vertex also has an encapsulated islet cell program in investigational new drug (IND)-enabling studies. They plan to file an IND in 2022 for the program, which could eliminate the need for immunosuppression in treatment.