19 October 2021 - - US-based biotechnology company Vertex Pharmaceuticals Inc. (NASDAQ: VRTX) has posted positive Day 90 data for the first patient from the Phase 1/2 clinical trial of VX-880, an investigational stem cell-derived, fully differentiated pancreatic islet cell replacement therapy for people with type 1 diabetes.

This is the first demonstration of a patient with T1D achieving robust restoration of islet cell function from such a cell therapy, the company said.

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.

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 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.

Based upon these data, Vertex plans to continue to progress the Phase 1/2 program for VX-880. There are multiple active sites in the US, and the Clinical Trial Application has been approved in Canada.

Vertex is also progressing IND-enabling studies for its encapsulated islet cell program, which would potentially eliminate the requirement for immunosuppression, and plans to file an IND for this program in 2022.

VX-880 is an investigational allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy manufactured using proprietary technology.

VX-880 is being evaluated for patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia.

According to the company, VX-880 has the potential to restore the body's ability to regulate glucose levels by restoring pancreatic islet cell function, including glucose responsive insulin production. VX-880 is delivered by an infusion into the hepatic portal vein and requires chronic immunosuppressive therapy to protect the islet cells from immune rejection.

The clinical trial is a Phase 1/2, multi-center, single-arm, open-label study in patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia.

This study is designed as a sequential, multi-part clinical trial to evaluate the safety and efficacy of VX-880. The first two patients will be treated with half the target dose, followed by dose escalation to the target dose in the subsequent patients.

Approximately 17 patients will be enrolled in the clinical trial. Enrollment is ongoing in this study.

T1D results from the autoimmune destruction of insulin-producing islet cells in the pancreas, leading to loss of insulin production and impairment of blood glucose control.

The absence of insulin leads to abnormalities in how the body processes nutrients, leading to high blood glucose levels. High blood glucose can lead to diabetic ketoacidosis and over time, to complications such as kidney disease/failure, eye disease (including vision loss), heart disease, stroke, nerve damage and even death.

Due to the limitations and complexities of insulin delivery systems, it can be difficult to achieve and maintain balance in glucose control in patients with T1D.

Hypoglycemia often results because of the difficulty in balancing the different factors that impact glucose levels, including insulin, diet and exercise.

Hypoglycemia remains a critical limiting factor in glycemic management, and severe hypoglycemia can cause loss of consciousness, coma, seizures, injury, and can be fatal.

Over time, patients with T1D can develop impaired awareness of hypoglycemia, meaning they are no longer able to perceive the early signs of a hypoglycemic event, which can be dangerous and result in life threatening events.

Current standards of care do not address the underlying causes of the disease, and there are limited treatment options beyond insulin for the management of T1D.