In groundbreaking results, Vertex Pharmaceuticals presented and published results showing that ten out of twelve patients in a small trial exhibited signs of a cure for their type 1 diabetes after receiving the stem cell therapy Zimislecel.
This is extremely exciting. While still early days for this therapy and there are some caveats (discussed below), my sense is that this therapy is likely on track to gain FDA approval in 2026.
So far Zimislecel appears safe and effective for type 1 diabetes
What is Zimislecel?
Originally called VX-880, it is an investigational stem cell-based therapy consisting of pancreatic progenitor cells.
The cells are delivered by an infusion into the hepatic portal vein, aiming for engraftment.
Here is the clinical trial listing: A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes. The short NEJM report, Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes, has some more details.
All participants:
- “Demonstrated engraftment with glucose-responsive endogenous C-peptide production, which was durable through one year of follow-up.
- Achieved the ADA targets of HbA1c <7% and time in range of >70%.
- Were free of SHEs from day 90 onwards.
- Had a reduction in exogenous insulin use (mean reduction in daily insulin dose: 92%).
- 10/12 (83%) no longer required exogenous insulin at Month 12.
- Achieved the Phase 1/2 primary endpoint of elimination of SHEs with HbA1c <7%.”
These are impressive efficacy outcomes so far.
Some caveats on this investigational Vertex cell therapy
It’s too soon to definitely say that Zimislecel is a cure more generally. As with many things, the full story here is complicated. What do we need to keep in mind?
Small study. More data are needed and this is a small study, but this is about as good as it gets at this stage.
Immunosuppression. The cells are allogeneic so recipients will likely have to take immunosuppressive therapy for the rest of their lives. If the graft is rejected, the benefit will disappear. Knocking down the immune system, especially indefinitely, can make people more prone to infections and cancer.
Unique group of diabetes patients. The dozen participants in this trial are not necessarily representative of type 1 diabetes patients more generally. All in this group had hypoglycemic unawareness. They don’t sense low blood sugar the way many people do.
Still, the data are quite exciting.
The history that led to Zimislecel
Until recently, there were several players in this arena including ViaCyte and Semma Therapeutics, founded by Doug Melton. Vertex acquired both firms and ultimately Melton went to work at Vertex. The different firms had somewhat distinct approaches to making the pancreatic cells from stem cells and delivering them.
For example, for a long time ViaCyte focused on an encapsulated cell therapy. While Vertex continued studying the encapsulation approach (VX-264) for a time, they discontinued that work a few months ago.
Another strong argument against banning hESC research funding
Very importantly, human embryonic stem cells (hESC) are the basis for Zimislecel.
This current promising trial outcome also brings to mind encouraging recent findings from two trials on stem cells for Parkinson’s, one using hIPSCs and one employing hESC. Overall, these three exciting trials highlight the importance of continuing federal funding of hESC research. Both Project 2025 and a group of conservative federal lawmakers have pressed Trump to ban hESC funding. We should advocate for continued research funding. Not everything can somehow simply pivot to hIPSCs.
Congratulations to Doug Melton, Vertex, and the whole team. Melton has been a driving force in this field.
Thanks, Jeanne.
So, Paul, two questions.
Does it have to be hESC cells? I can imagine you wouldn’t want to use some patients’ own iPSCs because their immune systems will kill them (which is, presumably, what caused the type 1 diabetes to begin with). But couldn’t you use someone else’s iPSCs? Of course, if all the research has been done with hESCs, it makes sense to continue with them, and I am NOT arguing for banning hESC research; just curious.
Second, is it possible that there is a sweet spot for iPSCs that are different enough from the patient to avoid auto-immune attack on new cells but similar enough at least to tamp down the regular immune attack on them, requiring less (or maybe ultimately no) immune suppression. Use iPSCs from someone close enough to be, say, a good solid organ donor?
Good questions. It likely does not have to be hESCs. It’s just not possible to pivot to hIPSCs after decades of work.
There is hIPSC-based work ongoing too but not so far along.
There might be a sweet spot like you described, but also using the patient’s own hIPSC might be fine too. The pancreatic cells made from them might not be subject to “regular immune attack” as you said.
Hank, the autoantibodies target proteins that are components of islet cells, not the major antigens that distinguish self from non-self, so using a close donor wouldn’t be better than using a person’s own iPSCs to make the islets.