Vertex’s cell therapy gives early hope for weaning some type 1 diabetes patients from insulin

A radical new way of treating type 1 diabetes keeps producing promising early data, raising hopes that a cell therapy might one day become a cure for the disease.

The data, from a small trial, are the most advanced clinical results yet from Vertex Pharmaceuticals’ VX-880 program, which consists of an infusion of lab-grown, insulin-producing cells made from stem cells. Most notably, the newest results include two patients with over a year of follow-up, each of whom have shown significant drops in their A1C blood sugar levels and no severe hypoglycemic events, and remain free from using insulin as of a May data cut-off. Data from three additional patients, who received the therapy more recently, are following a similar trajectory.

“This data is so clearly outside the range that you would ever see by chance,” David Altshuler, Vertex’s chief scientific officer, told Endpoints News in an advance interview. “That tells you there’s something real here.”

The patients came into the study with a history of recurring hypoglycemic events and requiring regular insulin injections.

David Altshuler

There are significant caveats. The study is small, with only six patients — one of whom withdrew from the study early. And it’s still too early to know how durable the treatment might be.

“It’s early,” Altshuler said. “We only have these six patients, and we need to just collect more data and follow over more time.”

But the results, which were presented Friday at the American Diabetes Association’s annual conference in San Diego, are almost certain to generate excitement, and Vertex said they were enough to move the Phase I/II trial to its third and final part, which will dose patients concurrently with the target dose. The study aims to enroll 17 volunteers in total.

There are more than a million people with type 1 diabetes in the US, and people with the disease are typically dependent on insulin treatments for life. The potential for a durable treatment, or even a cure, has made Vertex’s program one of the most closely followed in all of diabetes, especially after its first study volunteer was able to remain off insulin following a single infusion.

Cell therapy slashed blood-sugar levels as patients stay off insulin

Control of blood sugar levels, measured by A1C levels, is the gold standard of diabetes care. For the two patients treated more than a year ago, both saw their A1C levels fall significantly while remaining insulin independent.

One patient’s A1C level went from 8.6% before treatment to 5.3% after 21 months, while the other trial volunteer saw their A1C decrease from 7.6% to 6.0% at 12 months. In general, the goal for people with diabetes is an A1C level below 7.0%, according to the American Diabetes Association, and a 7.0% range is still elevated and associated with symptoms, Altshuler said. A normal level is below 5.7%.

While the science of turning stem cells into pancreatic cells that pump out insulin is remarkably complex, the premise behind Vertex’s therapy is simple. Type 1 diabetes is an autoimmune disease in which a person’s immune system attacks and destroys its body’s own insulin-making cells. For the last century, routine insulin injections have been the standard. Vertex’s program infuses lab-made, insulin-producing cells, coupled with immunosuppressives to prevent the body from attacking them.

“We’re now able to see with these cells that they work, they work consistently, and the long-term follow-up is very positive,” said Felicia Pagliuca, Vertex’s disease area executive for type 1 diabetes. “It gives us a lot of reason for hope.”

Irl Hirsch, a professor at the University of Washington’s diabetes institute, said immunosuppression is one of his concerns because of heightened risk of infections and long-term malignancies. At the same time, he called Vertex’s data impressive and an “exciting incremental step forward.” While there are roughly 2.5 million people with type 1 diabetes in the US and Europe, Altshuler estimates just 60,000 people, or about 2% of the type 1 population, would meet the criteria for VX-880.

Despite that limitation on VX-880, Vertex hopes to replicate its cystic fibrosis playbook in type 1 by developing a range of medicines to address more and more patients over time.

Kalydeco, Vertex’s first CF drug, initially launched for only 2,000 patients. Vertex now sells a suite of CF drugs that treat about 90% of the population, with an experimental medicine in the clinic for the last 10%.

“VX-880 is like Kalydeco, we hope,” Altshuler said. “It’s the medicine that proves you can do something that no one thought was possible.”

Moving beyond immunosuppressants

Vertex’s other cell therapy programs aim to work without immunosuppressants. One therapy, called VX-264, includes the same cells as VX-880 along with an immune-cloaking device. VX-264 is just now entering the clinic, with the study enrolling volunteers in Canada and US enrollment expected to begin shortly.

Even earlier in development, Vertex is investigating ways to genetically edit cells to hide them from the immune system. Vertex paid $100 million upfront earlier this year to use CRISPR Therapeutics’ gene-editing technology in type 1 diabetes. That research is without a timeline to entering the clinic.

Altshuler, an endocrinologist by training, said he was shocked by how little industry interest there had been historically in new type 1 therapies.

“There seemed to be a disconnect between what companies were thinking was the unmet need — maybe because they were selling a lot of insulin — and what patients were actually experiencing,” he said.

Vertex’s success has also drawn more industry eyes to the cell therapy idea. The startup Sana Biotechnology hopes to file an IND next year for its own type 1 cell therapy program, and the legacy insulin makers Eli Lilly and Novo Nordisk both have ongoing, preclinical projects. While Altshuler acknowledged the increasing competition, he said he’s confident in Vertex’s ability to say ahead.

“The combination of our strategy and our capabilities, but also frankly, our time horizon and our resources and our experience puts us in a unique position compared to someone, for example, who sells insulin,” Altshuler said. “They may have salespeople and stuff like that, but this is an entirely different therapy.”

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