One challenge of using cell therapy to treat type 1 diabetes is that this approach requires chronic suppression of the immune system to prevent rejection of donor cells. A Vertex Pharmaceuticals therapeutic candidate designed to avoid immunosuppression has fallen short of its efficacy goals in a clinical trial, leading the drugmaker to discontinue the program.
The Boston-based drugmaker’s announcement after the market close Friday offered few details about the missed efficacy in the Phase 1/2 test of the cell therapy, VX-264. However, the cells that make up this cell therapy may yet reach certain type 1 diabetes patients in another way.
In type 1 diabetes, the immune system mistakenly attacks insulin-producing islet cells. With cell therapy, transplanted cells are intended to bring patients some of the insulin production they’ve lost. So far, the only FDA-approved cell therapy for type 1 diabetes is Lantidra, which CellTrans makes with pancreatic cells sourced from deceased donors. While clinical testing showed benefit lasting years, patients treated with the CellTrans therapy must also receive chronic immunosuppression, which introduces problems such as a higher risk of developing infections.
With VX-264, Vertex aimed to replace the insulin production lost to type 1 diabetes with islet cells derived from donor stem cells. The therapy is encapsulated in an implantable medical device that protects the cells from the immune system. Vertex tested this therapy in a Phase 1/2 study with a targeted enrollment of 17 patients.
Vertex said VX-264, was safe and well tolerated by patients. Beyond assessing safety, the main goal of this open-label study was to measure the change in C-peptide, a peptide that is released along with insulin. Measuring C-peptide levels is a way to gauge insulin production. In the VX-264 study, this measure was taken at day 90. Without disclosing specific figures, Vertex said increases in C-peptide “were not observed at levels necessary to deliver benefit.” The company added that it plans further analyses of the results, including examination of the devices removed from 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 a protective medical device. Participants must receive immunosuppression. But this approach, currently in Phase 3 testing, could help patients with more severe disease. Vertex said the pivotal study is on track to complete enrollment and dosing in the first half of this year, potentially positioning the therapy for global regulatory submissions next year. If approved, the company estimates zimislecel could help about 60,000 patients with severe type 1 diabetes.
In a note sent to investors, William Blair analyst Myles Minter said the clinical trial failure of VX-264 is disappointing, as this cell therapy/device combination could have expanded the addressable type 1 diabetes market beyond the severe disease market that Vertex is targeting with naked zimislecel.
“Vertex’s prioritization on the clinical advancement and potential launch of zimislecel for 60,000 severe T1D (type 1 diabetes) patients is prudent given the positive data to date, and approval in the T1D space would serve to further the company’s diversity of commercial assets beyond cystic fibrosis and acute pain,” he said.
Minter acknowledged the excitement earlier this year surrounding UP421, a Sana Biotechnology cell therapy made with hypoimmune technology that engineers cells to avoid detection by the immune system. But the encouraging data reported for this experimental Sana therapy came from a single patient after four weeks of treatment with a very low cell dose, he said. The Sana therapy needs data from more patients and longer follow-up to show whether these cells can provide long-term evasion of the immune system.
VX-264 and zimislecel came from Vertex’s 2019 acquisition of privately held Semma Therapeutics. The $950 million acquisition established Vertex’s presence in type 1 diabetes therapy R&D. In 2022, Vertex spread its bets in the disease with the $320 million acquisition of ViaCyte, which brought three type 1 diabetes programs, including a gene-edited therapy in development under a partnership with CRISPR Therapeutics. Last year, Vertex’s ViaCyte subsidiary opted out of the collaboration with CRISPR Therapeutics to co-develop a gene-edited stem cell therapy for diabetes. Instead, Vertex is focusing on applying CRISPR gene-editing to zimislecel before those cells differentiate into islet cells. This approach, currently preclinical, is intended to cloak the cells from the immune system.
In a regulatory filing, Vertex said it expects to record a $400 million asset impairment charge related to the discontinued VX-264 program. The company plans to disclose results from the impairment analysis in its upcoming report of financial results for the first quarter of 2025.
Photo: David L. Ryan/The Boston Globe, via Getty Images