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 exhibits promise as a practical “remedy” for sort 1 diabetes.
- New information exhibits that examine contributors skilled important enhancements in A1C, glucose management, and a diminished want for insulin.
- The VX-880 trial was placed on maintain earlier in 2024 resulting from two participant deaths. The deaths at the moment are believed to be unrelated to the examine drug.
Vertex offered new information this week at EASD 2024 in Madrid on its carefully watched scientific trial VX-880, hailed as a doubtlessly revolutionary therapy for folks with sort 1 diabetes. The trial, which was paused earlier this 12 months following the deaths of two contributors, has now resumed and is actively recruiting.
Although the examine remains to be in its early phases, the outcomes have been promising. All 12 contributors who obtained 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 contributors had both a diminished want or full elimination of exogenous insulin (that means injectable insulin not naturally produced by the physique). As well as, all contributors skilled important enhancements in A1C, time in vary, in addition to a diminished 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 Middle in Toronto. “You’ll be able to 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 better than 90% time in vary with once more no proof of any extreme hypoglycemic episodes.”
Of the 4 contributors 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 practical “remedy” for sort 1 diabetes.
Earlier than therapy with VX-880, all examine contributors produced zero insulin and had a historical past of extreme, recurring episodes of hypoglycemia. Three months after cell transplantation, contributors 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 contributors died. Neither dying 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 important following VX-880, however since excessive dose steroids additionally decrease the immune system, it might 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 particular person “cured” of sort 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 observe, 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 sort 1 diabetes. This could 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 finally 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 achieve from any such 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 contributors within the trial had been offered by Dr. James Markmann, chief of the division of transplant surgical procedure at Massachusetts Basic Hospital, on the 2022 American Diabetes Affiliation (ADA) convention.
Within the first section of the trial, every participant was given half the dose of beta cells estimated to be required. A standard follow in a majority of these research is beginning with half the anticipated dose and growing it because the trial progresses.
The next outcomes present astonishing enhancements in A1C, time in vary, and diminished 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 a “customary” insulin dose, as every day insulin doses are decided by a healthcare supplier primarily based on the wants of every particular person. To place this in perspective, right here’s a better have a look at a few of the information from two contributors.
Participant 1
| Examine day | Day 0 (baseline) | Day 121-150 | Day 241-270 |
| Day by 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
| Examine day | Day 0 (baseline) | Day 121-150 |
| Day by 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.
Thus far, the protection profile of VX-880 is much like what could be anticipated given the usage of immunosuppressants, the surgical process to implant the cells, and the contributors’ medical historical past.
Following the current constructive outcomes offered at EASD 2024, the examine shouldn’t be solely ongoing however is recruiting extra contributors. Proper now, there are 14 contributors within the VX-880 trial and Reichman mentioned they’re seeking to up the quantity to 37 (see right here for particulars on enroll).
The info additionally exhibits promise for VX-264, one other new Vertex stem cell therapy that doesn’t require immunosuppression at the moment being investigated in scientific trials.
When will this change into obtainable to extra folks with sort 1 diabetes?
In contrast to different interventions, comparable 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 obtainable, so provide is a major drawback,” Markmann mentioned. “One of the crucial necessary points of this work is that there might be a limiteless provide of beta cells for transplantation going ahead.”
Whereas the outcomes up to now are thrilling, analysis remains to be within the early phases. The present trial is anticipated to wrap up in 2030, and extra research with bigger pattern sizes would want to observe. After all the research are accomplished, Vertex must submit an utility to the FDA earlier than it may be permitted to be used.
“That is groundbreaking work and an actual leap ahead for the sector,” mentioned Markmann. “Whereas we can’t say precisely when this may change into obtainable, we’re a lot nearer to a practical remedy for sort 1 diabetes than we had been earlier than this method.”
