This content material initially appeared on diaTribe. Republished with permission.
By Anna Brooks & Andrew Briskin
Key takeaways:
- VX-880 is an investigational stem cell remedy by Vertex that reveals promise as a purposeful “treatment” for kind 1 diabetes.
- New information reveals that examine members skilled vital enhancements in A1C, glucose management, and a lowered want for insulin.
- The VX-880 trial was placed on maintain earlier in 2024 as a result of two participant deaths. The deaths are actually believed to be unrelated to the examine drug.
Vertex introduced new information this week at EASD 2024 in Madrid on its intently watched scientific trial VX-880, hailed as a probably revolutionary therapy for folks with kind 1 diabetes. The trial, which was paused earlier this 12 months following the deaths of two members, has now resumed and is actively recruiting.
Although the examine continues to be in its early phases, the outcomes have been promising. All 12 members who acquired a full dose of VX-880 noticed a discount in A1C of lower than 7% and not skilled extreme hypoglycemia (low blood sugar). Eleven of the 12 members had both a lowered want or full elimination of exogenous insulin (that means injectable insulin not naturally produced by the physique). As well as, all members skilled vital enhancements in A1C, time in vary, in addition to a lowered want for insulin injections.
“At baseline, all enrollees had pretty poor management with a time in vary of lower than 50%,” mentioned Dr. Trevor Reichman, surgical director of pancreas and islet cell transplantation on the Ajmera Transplant Heart in Toronto. “You possibly can see in a short time after a full dose of VX-880 all recipients had enhancements. And as far out as one 12 months, we see larger than 90% time in vary with once more no proof of any extreme hypoglycemic episodes.”
Of the 4 members who handed the one-year mark following therapy, all achieved insulin independence and maintained an A1C of lower than 7%. This means that VX-880 could possibly be a much-awaited purposeful “treatment” for kind 1 diabetes.
Earlier than therapy with VX-880, all examine members produced zero insulin and had a historical past of extreme, recurring episodes of hypoglycemia. Three months after cell transplantation, members exhibited insulin manufacturing that efficiently responded to glucose.
Participant deaths: what occurred?
Regardless of constructive leads to the early phases of the VX-880 trial, Vertex halted the examine in January 2024 after two members died. Neither loss of life is believed to be associated to VX-880.
One participant died of meningitis after a sinus surgical procedure unrelated to the examine. Reichman defined that the participant had been given a excessive dose of steroids earlier than and after the process (steroids are poisonous to islets aka insulin-producing cells within the pancreas). The participant was additionally on immunosuppressants, which is critical following VX-880, however since excessive dose steroids additionally decrease the immune system, it may have left them weak to an infection.
The opposite participant died from a traumatic mind harm following a motorbike accident brought on by a extreme episode of hypoglycemia.
One participant stays unknown however the different, Brian Shelton, 66, was mentioned to be the primary individual “cured” of kind 1 diabetes with VX-880. Shelton efficiently began producing his personal insulin in 2021 six months after the investigational therapy.
Although the trial is again on monitor, it’s unclear if the three-month pause will have an effect on Vertex’s timeline for finishing the scientific trial.
What’s VX-880 remedy?
A kind of experimental stem cell remedy, VX-880 goals to revive pure insulin manufacturing in folks with kind 1 diabetes. This may end in a drastic enchancment in high quality of life as these with the illness would not require insulin or expertise extreme, typically life-threatening, episodes of hypoglycemia.
Stem cell therapies like VX-880 work by transplanting wholesome insulin-producing cells into the physique. If profitable, the brand new cells would change non-functioning ones and in the end restore insulin manufacturing.
Much like individuals who obtain organ transplants, these handled with VX-880 should take immunosuppressants to forestall the immune system from rejecting new beta cells.
Due to the chance of an infection related to immunosuppressants, solely these with extreme hypoglycemia unawareness have been eligible for Vertex’s trial. It is because these candidates have essentially the most to realize from this kind of remedy, given the dangers related to hypoglycemia unawareness.
The historical past behind VX-880
Vertex first introduced the event of VX-880 in 2021. Information from the primary two members within the trial had been introduced by Dr. James Markmann, chief of the division of transplant surgical procedure at Massachusetts Common Hospital, on the 2022 American Diabetes Affiliation (ADA) convention.
Within the first part of the trial, every participant was given half the dose of beta cells estimated to be required. A standard apply in these kind of research is beginning with half the anticipated dose and rising it because the trial progresses.
The next outcomes present astonishing enhancements in A1C, time in vary, and lowered insulin wants for every participant. For reference, the ADA Requirements of Care recommends a goal time in vary of 70% (70-180 mg/dL). There isn’t any “commonplace” insulin dose, as each day insulin doses are decided by a healthcare supplier based mostly on the wants of every particular person. To place this in perspective, right here’s a more in-depth take a look at a number of the information from two members.
Participant 1
| Research day | Day 0 (baseline) | Day 121-150 | Day 241-270 |
| Each day Insulin dose | 34 models | 2.6 models | 0 models |
| Time in Vary | 40.1% | 81.4% | 99.9% |
| A1C | 8.6% | 6.7% | 5.2% |
Participant 2
| Research day | Day 0 (baseline) | Day 121-150 |
| Each day Insulin dose | 25.9 models | 18.2 models |
| Time in Vary | 35.9% | 51.9% |
| A1C | 7.5% | 7.1% |
The way forward for VX-880
Whereas there was preliminary concern concerning the two participant deaths being associated to the VX-880 process, Reichman mentioned that no extreme antagonistic occasions had been associated to the islet cells themselves.
To this point, the security profile of VX-880 is just like what can be anticipated given using immunosuppressants, the surgical process to implant the cells, and the members’ medical historical past.
Following the current constructive outcomes introduced at EASD 2024, the examine will not be solely ongoing however is recruiting extra members. Proper now, there are 14 members within the VX-880 trial and Reichman mentioned they’re seeking to up the quantity to 37 (see right here for particulars on the best way to enroll).
The info additionally reveals promise for VX-264, one other new Vertex stem cell therapy that doesn’t require immunosuppression presently being investigated in scientific trials.
When will this turn into accessible to extra folks with kind 1 diabetes?
In contrast to different interventions, corresponding to pancreas transplants or beta cell islet transplants from human donors, VX-880 has the potential for use on a a lot bigger scale.
“Proper now within the U.S., there are solely about 1,000 pancreas transplants accessible, so provide is a major downside,” Markmann mentioned. “Probably the most vital features of this work is that there will be an infinite provide of beta cells for transplantation going ahead.”
Whereas the outcomes to date are thrilling, analysis continues to be within the early phases. The present trial is anticipated to wrap up in 2030, and extra research with bigger pattern sizes would wish to observe. After the entire research are accomplished, Vertex must submit an software to the FDA earlier than it may be accepted to be used.
“That is groundbreaking work and an actual leap ahead for the sphere,” mentioned Markmann. “Whereas we can’t say precisely when this can turn into accessible, we’re a lot nearer to a purposeful treatment for kind 1 diabetes than we had been earlier than this method.”
