Apex Cell Therapy Missed the Clinic, but there are other shots on the Target of Type 1 Diabetes
One challenge in the use of cell therapy for type 1 diabetes is that this approach requires chronic inhibition of the immune system to prevent the inhibition of donor cells. The candidates for treatment of Vertex Pharmaceuticals, designed to avoid immunosuppression, failed to meet their efficacy goals in clinical trials, resulting in the drug manufacturer halting the program.
The Boston-based drugmaker’s announcement after the market closure on Friday provided details about the efficacy of the 1/2 phase of cell therapy testing, VX-264. However, the cells that make up the cell therapy may reach certain types of patients with type 1 diabetes in another way.
In type 1 diabetes, the immune system mistakenly attacks the islet cells that produce insulin. Through cell therapy, transplanted cells are designed to cause the patient to lose some of the production of insulin. So far, the FDA-approved cellular therapy for type 1 diabetes is Lantidra, which is performed through pancreatic cells produced from the deceased donor. While clinical testing has shown lasting benefits, patients treated with cell therapy must also undergo chronic immunosuppression, which introduces problems such as higher risk of developing infection.
Using VX-264, the apex was designed to replace insulin production lost to type 1 diabetes with islet cells derived from donor stem cells. The therapy is encapsulated in an implantable medical device to protect cells from the immune system. Vertex tested the therapy in a Phase 1/2 study with targeted enrollment in 17 patients.
Vertex says the VX-264 is a safe and well-tolerated VX-264. In addition to assessing safety, the main goal of this open-label study was to measure changes in C peptide, a peptide released with insulin. Measuring C peptide levels is one way to measure insulin production. In the VX-264 study, the measure was conducted on day 90. Without disclosing specific numbers, Vertex said the increase in C peptide was “not observed at the necessary level to provide benefits.” The company added that it plans to further analyze the results, including examining the devices removed from the study participants.
The cell therapy in VX-264 is Zimislecel (formerly VX-880). A separate vertex program is evaluating Zimislecel as a “naked” cell therapy without encapsulation in protective medical devices. Participants must undergo immunosuppression. However, the method currently underway for the third phase of testing can help patients with more serious illnesses. Vertex said the key study is being planned for completion and administration in the first half of this year, and it is possible to target treatment in next year's global regulatory introduction. If approved, the company estimates that Zimislecel can help about 60,000 people with severe type 1 diabetes.
William Blair analyst Myles Minter said in a note sent to investors that the failure of the VX-264 clinical trial is disappointing because this combination of cellular therapy/device could expand the addressable type 1 diabetes market beyond the severe disease market, while Vertex's exposed Zimislecel targeting.
“Given the positive data to date, Zimislecel's clinical advancement and potential priority of potential rollouts in 60,000 patients with severe T1D (type 1 diabetes) is prudent, and the approval of the T1D space will further promote the company's diversity beyond cystic fibrosis and acute pain, which will further promote the company's diversity,” he said.
Minter acknowledged the excitement surrounding UP421 earlier this year, a SANA biotechnology cell therapy made from low immunity technology that engineers avoid passing immune system testing. But encouraging data on this experimental SANA therapy came from a patient who had been treated with four weeks of cell doses, he said. SANA treatment requires more patient data and longer follow-up to show whether these cells can evade the immune system for a long time.
VX-264 and Zimislecel are from Vertex's 2019 acquisition of privately held Semma Therapeutics. The $950 million acquisition establishes Vertex's presence in the development of type 1 diabetes treatment. In 2022, Vertex bets on the disease with a $320 million acquisition of Viocyte, which brings three type 1 diabetes programs, including gene therapies developed in collaboration with CRISPR Therapeutics. Last year, Vertex's Viocyte subsidiary chose to work with CRISPR Therapeutics to jointly develop stem cell therapies for gene editing of diabetes. Instead, before these cells differentiate into islet cells, the apex was focusing on applying CRISPR gene editing to Zimislecel. Current preclinical approaches aim to mask cells from the immune system.
Vertex said in regulatory filings that it is expected to record $400 million in asset damage allegations related to the terminated VX-264 program. The company plans to disclose the results of the damage analysis in its upcoming financial results report in the first quarter of 2025.
Photo: David L. Ryan/Boston Globe, via Getty Images
