Vertex T1D Trial Moves into Phase III

November 21, 2024

Earlier this month during an earnings update, Vertex Pharmaceuticals announced that its phase I/II T1D clinical trial, VX-880, was approved by the FDA to move into phase III. Phase III is often the last—or one of the last—regulatory approval steps before attaining market approval.
 
This is significant news.
 
Although VX-880 is not a Practical Cure project, Vertex is uniquely positioned to tackle the cell supply issue head-on if the therapy is successful and sent to market. Furthermore, these same cells are being tested in two other T1D projects, one qualifying as a Practical Cure. The following provides a quick review of VX-880 and a point of view about the potential and challenges of this news.
 

Brief Background on VX-880

The VX-880 trial utilizes a proprietary line of stem cell-derived (sBC) islets that are infused into the patient’s liver to replace insulin-producing cells lost following the T1D autoimmune attack. The cell line is derived from a single embryonic stem cell that can be replicated indefinitely. Semma Therapeutics, founded by Harvard professor Doug Melton, was the original developer of this cell line before Vertex acquired the company in 2019.
 
Vertex has distributed positive, regular updates on VX-880 since its inception. This is notable, as many trials go years without publicizing interim results. The news surrounding VX-880 has been both groundbreaking and somewhat controversial. On one hand, the cells have been proven safe and effective at establishing insulin independence in several patients, earning expanded enrollment.
 
On the other hand, patients in this study are required to take broad immunosuppressive drugs that weaken the overall immune system. To this point, the FDA temporarily placed the trial on clinical hold in January of this year after two patients died. Within a few months, the FDA determined that the deaths were unrelated to transplanted cells and the trial was cleared to resume. However, one death was due to Cryptococcal Meningitis, an infection affecting those with compromised immune systems, underscoring the heavy risk of broad immunosuppression.
 

Is It a Practical Cure?

This phase III trial is not a Practical Cure for T1D. As long as broad immunosuppression is required, it is not an option that most people with T1D would choose. Broad immunosuppression, which must be taken daily, weakens the immune system and reduces a person’s resistance to disease and infection, including an increased risk of cancer. Even if there was an ample supply of insulin-producing cells for transplant and it was affordable, most would not take the risk.
 
Although VX-880 is not a Practical Cure, these same cells are being tested in two other research initiatives on the road to a Practical Cure. In both initiatives, the VX-880 cells act as the foundation, and the viability of these cells should translate. If the cells continue successfully producing insulin and are protected from the immune system’s attack without broad immunosuppression, we could see a Practical Cure.

VX-880 in Three Research Initiatives 
There are currently three Vertex research initiatives utilizing VX-880 islet cells.

1. VX-880 (phase III): Infusion of stem cell-derived islets into the liver. The cells are protected by immunosuppression and the treatment is intended for patients with established T1D and severe hypoglycemia.
2. VX-264 (phase I/II): The same cells used in VX-880 are protected by an encapsulation device—without immunosuppression—and transplanted into the body. This qualifies as a Practical Cure project. Initial results are expected in 2025.
3. Hypoimmune Cells (in development): In collaboration with CRISPR Therapeutics, Vertex aims to use gene-editing techniques to cloak VX-880 cells from the immune system, negating the need for immunosuppression.

VX-880: Can It Solve Cell Supply?

Although not a Practical Cure, moving Vertex’s cell line to market may solve the cell supply problem.
 
There are two hurdles that must be overcome: Cell supply and cell protection. Without protection, transplanted cells will die. Without sufficient cell supply, transplantations are limited and expensive.
 
These limitations also impact researchers who have difficulty getting healthy human islet cells for autoimmune resistance testing. Today, the only source of islets for research comes from the limited supply of recently deceased cadavers. The process of harvesting, preparing, and transporting cells is not only expensive and time consuming, but is completely reliant on donor availability.   
 
If the VX-880 cells are made at scale, the rigid limitations of cadaverous sourced cells would be a thing of the past. The cells would be widely available for anyone willing to purchase them. Significantly more researchers, from graduate assistants to seasoned principal investigators, would be able to use functional, insulin-producing islet cells to solve the autoimmune attack. Available supply could be the catalyst to a wave of increased autoimmune testing and cure research.
 
Vertex is positioning itself to manufacture VX-880 cells on an industrial scale if the therapy gains FDA approval. It has two complementing partnerships dedicated to manufacturing the company’s proprietary line of sBCs on a commercial level:

1. Lonza Bioscience: Broke ground in August 2023 on a New Hampshire facility dedicated to mass-producing Vertex’s sBCs.
2. TreeFrog Therapeutics: Began collaboration in April 2024. TreeFrog’s C-Stem technology will be used to “produce and amplify cells for Vertex’s T1D therapies,” which they hope will enable faster manufacturing speed while maintaining quality and consistency.

What Are the Next Steps?

Vertex has just announced the phase III trial, and much is still unknown. The official start and end dates of the trial have not been disclosed, but we can expect the timing to move quickly, and Vertex will likely continue sharing regular interim results as it has done in the past.
 
The trial will include fifty patients, and the primary endpoints of the new trial will be 1) the proportion of patients who achieve insulin independence (at the twelve-month appointment), and 2) the absence of severe hypoglycemic events.
 
One encouraging factor is that Vertex, as a private company, has regular pressure from its investors to deliver an economic return on investment, which means the company has ample incentive to demonstrate progress quickly.
 
JDCA will keep you posted on the latest T1D developments as they progress.