ADA 2023 – Vertex raises hopes of type 1 diabetes cure

But it still has a long way to go with its islet cell therapies.

Vertex’s $1bn purchase of Semma Therapeutics four years ago was a bold bet on cell therapies for type 1 diabetes. And the latest results with the most advanced project from the deal, VX-880, have raised hopes of a functional cure.

However, the data presented at ADA over the weekend come from just six patients, and only two of these have been followed for a year or more. Although the results look promising, Vertex will have to replicate them in many more patients, and show that the effect is durable. There is also the question of how VX-880 will fit in as Vertex’s other diabetes cell therapy candidates evolve.

Insulin independent

VX-880 comprises “naked” allogeneic pancreatic islet cells that are said to be able to detect glucose levels and release insulin in response. It requires immunosuppression to prevent rejection of the cells.

The most exciting finding from ADA was that the two patients followed for one year or longer became insulin independent. They also met the primary endpoint, elimination of severe hypoglycaemic events between day 90 and month 12, with HbA1c levels of less than 7%.

HbA1c reductions with VX-880

Source: ADA.

One of these patients was in part A of the phase 1/2 trial, receiving half the target dose of VX-880, while the other was in part B, receiving a full target dose.

However, another patient in part A discontinued after receiving a second half dose at nine months, and was not evaluable for the primary endpoint. Vertex did not say why this patient withdrew, except that this was not down to adverse events.

While this patient showed improvements in HbA1c, they were still taking insulin at the latest assessment.

Insulin reductions with VX-880

Source: ADA.

As for notable side effects, there were two cases of transaminase elevations considered related to VX-880, but both were transient and resolved. There were no treatment-related serious adverse events, Vertex said.

The company is now moving to part C of the trial, which involves concurrent dosing of patients at the full target dose.

SVB analysts flagged several key unknowns for VX-880: the feasibility of large-scale production; how long the project will show an effect; and the path towards FDA filing. On the first point, Vertex today announced a collaboration with Lonza on a dedicated cell therapy manufacturing site.

There is also the question of whether patients will accept long-term immunosuppression and the risks this brings.

Enter Vertex’s second islet project, VX-264, an encapsulated cell therapy designed to avoid the need for immunosuppression, which recently went into phase 1/2.

Vertex also signed up Crispr Therapeutics in March to develop a gene editing method to produce “hypoimmune” cells that do not require encapsulation or immunosuppression. These are still at the research stage, although a hypoimmune cell project being developed by Crispr and Viacyte – which Vertex acquired last year – is in the clinic.

Vertex is not the only one shooting for a functional cure for type 1 diabetes. Sernova also had data at ADA with its islet project, the cell pouch system. The group said the first five patients treated in a phase 1/2 trial had achieved insulin independence, but conceded that subjects had needed "modest islet top-up". A second cohort, using higher-capacity cell pouches, has enrolled five of seven planned patients; more data are expected this year.

And, while Biomea stopped short of claiming that its menin inhibitor BMF-219 was a functional cure, it did suggest at ADA that it was disease-modifying in type 2 diabetes. All these projects will need much more evidence to convince.

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