Vertex T1D Trial Paused After 2 Unrelated Patient Deaths, CRISPR Collab Ends Next Day

January 16, 2024

Vertex Pharmaceuticals has garnered much attention in the news over the past couple of days, following its January 7 press release that announced program updates the day before its presentation at the 42nd Annual J.P. Morgan Healthcare Conference. These statements were primarily positive, detailing the projected future success of its FDA-approved drug developed with CRISPR Therapeutics, Casgevy.

The T1D news was mixed.

The press release provided an update on Vertex’s phase I/II human clinical trials of VX-880, which has been placed on a protocol-specified pause after the unrelated deaths of two study participants. This trial has been noteworthy over the past several years as the first proof of concept of the potential impact of stem cell-derived beta cells (sBCs). One of the participants who sadly passed was a lifelong member of the T1D community: Brian Shelton. Brian was featured in various national publications (i.e., the New York Times) after becoming the first insulin-independent patient following the treatment.

The following day, CRISPR Therapeutics published a press release regarding strategic priorities moving into 2024, including Vertex’s (via ViaCyte) decision to opt out of their agreement to co-develop and co-commercialize gene-edited therapies for diabetes. This decision will have immediate effect on the T1D clinical trial VCTX-211, renamed “CTX-211.” 

The upcoming hurdles are to be expected. The questions of if and when VX-880 will resume testing and why Vertex prematurely ended its agreement with CRISPR, are heavy in the air. Most importantly, how will these developments affect Vertex’s ability to advance research toward a Practical Cure?

This report will provide a quick update on the VX-880 trial, address the impact on a concurrent T1D trial called VX-264, and detail how the change in Vertex’s relationship with CRISPR Therapeutics will impact future collaborations.

Vertex VX-880

Vertex is renowned for its multi-faceted pipeline of research projects developing therapies for serious, chronic diseases. One branch of this pipeline is dedicated to type 1 diabetes, and its most promising therapy is VX-880, now placed on a protocol pause following the unrelated deaths of two study participants. The cause of death for both patients is unknown at this time, but the company is adamant that these deaths are unrelated to the trial.

This pause was implemented by Vertex and will proceed with data collection and reviews of the study by the independent data monitoring committee and global regulators, assessing safety and efficacy of the drug. This is a typical action after facing this type of issue, and although we expect this will not be permanent, the expected duration of the pause is still uncertain.

What Is VX-880?
VX-880 is a phase I/II study testing Vertex’s proprietary line of insulin-producing sBCs that are infused into the body’s liver. Lifelong immunosuppression is required to protect the cells from the body’s immune attack. Currently, there are three parts of this trial: A, B, and C, beginning at staggering times. To date, all 17 enrolled participants can produce some level of their own insulin, and all participants in A and B (omitting one who withdrew from the study) no longer require insulin injections and hit HbA1C levels <7%. According to Vertex's press release, "The safety profile of VX-880 to date is consistent with immunosuppressives, the perioperative period and past medical history."

VX-264
Vertex's VX-264 is another T1D therapy that began testing in March 2023, utilizing the same sBCs as VX-880. VX-264 is an early-stage investigational therapy in phase I/II clinical trials, differing from VX-880 in that the cells are placed in a protective encapsulation device and surgically implanted into the body. The goal of this trial is to eliminate the need for a patient to take chronic immunosuppressants to keep transplanted beta cells alive, as antirejection drugs put patients at risk of serious adverse side effects. This trial has the potential to be a Practical/Functional Cure for T1D.

Vertex stated by email that the trial VX-264, a project on our 2023 Practical Cure list, will not be impacted by the VX-880 pause.

CRISPR Therapeutics

CRISPR Therapeutics is a leader in scientific research for its novel CRISPR/Cas9 gene-editing technology and has been collaborating with Vertex on several facets of its pipeline since 2015. One high-profile outcome of that partnership produced Casgevy: a gene-edited cell therapy for the treatment of sickle-cell disease and TDT. Casgevy was FDA-approved on December 8, 2023, taking the limelight in Vertex’s presentation at the J.P. Morgan Health Care Conference.

At the same time, CRISPR Therapeutics announced that Vertex prematurely ended their agreement to co-develop specific cell protection solutions for T1D. This agreement was initially made between ViaCyte and CRISPR in 2018 to develop an immune-evasive stem cell line (PEC), later inherited and upheld by Vertex upon ViaCyte’s 2022 acquisition.

Because Vertex opted out of the agreement, any and all ongoing assets of the collaboration, including VCTX-211, are now wholly owned by CRISPR Therapeutics, subject to paying royalties on future products. Since this arrangement was held by the subsidiary ViaCyte, this decision should have no impact on Vertex’s clinical trials or research listed under the Vertex name.

Separate from Vertex’s collaboration via ViaCyte, Vertex entered into a $170 million deal with CRISPR Therapeutics in March 2023 to create hypoimmune cells that evade autoimmune attack. Vertex is continuing its non-exclusive rights to CRISPR Therapeutics’ CRISPR/Cas9 gene-editing technology to accelerate a potential cure for T1D, and this is not affected by the end of the ViaCyte collaboration.

VCTX-211 = CTX-211
VCTX-211, renamed “CTX-211,” is now wholly owned by CRISPR Therapeutics. It is a phase I clinical trial studying the safety and efficacy of gene-edited sBCs that are placed into an encapsulation device and transplanted into the body. This aims to eliminate required immunosuppression during islet transplantation, as the regiment of anti-rejection drugs is unreasonable for the majority of the T1D community. CRISPR Therapeutics stated it remains “committed to its goal of developing a beta-cell replacement product that does not require chronic immunosuppression,” leaving optimism that, for now, the company intends to continue dedicating resources to T1D.

There is no clarification as to why Vertex decided to opt out of its agreement with CRISPR Therapeutics. However, it is arguable that Vertex may have seen VCTX-211 as more of a liability than a gilded research avenue. VX-880 began clinical trials a year before VCTX-210a (the precursor to VCTX-211/CTX-211). In that time VX-880 has made continued measurable progress, whereas VCTX-210a has had no coverage updating the public on positive advancements, even upon trial completion.

Note: Vertex acquired ViaCyte in July 2022. Today, ViaCyte is a subsidiary of Vertex and cannot act independently. Intellectual resources and assets under the name “ViaCyte” are considered separate from those owned directly by Vertex in collaborative agreements.