Did Vertex stir up the situation in type 1 diabetes?

As semaglutide and tirzepatide, under the halo of "miracle weight - loss drugs", sweep the global market with continuous upgrades in targets, dosage forms, and efficacy, the plight of another group of diabetes patients seems to be overshadowed by this "technological carnival" —

There are approximately 9.15 million type 1 diabetes (T1D) patients globally. They have to be accompanied by insulin injection pens and blood glucose monitors every day. A slight negligence may endanger their lives due to severe hypoglycemia or hyperglycemia - related complications.

It was not until a few months ago that a set of data presented by Vertex at the ADA annual meeting brought this field into the spotlight: In the phase 1/2 clinical trial of its stem - cell therapy Zimislecel for T1D, 83% (10 out of 12) of the patients were completely free from insulin dependence one year after injection, and no fatal hypoglycemia occurred.

More importantly, this therapy does not rely on scarce donated islets. Instead, it generates islets through in - vitro differentiation of stem cells. If it is successfully submitted for market approval in 2026, it may completely rewrite the treatment landscape of T1D.

Although it remains to be confirmed by the final clinical data, and there are safety issues associated with the long - term combined use of Zimislecel and immunosuppressants, it is still a direct challenge to a century - old treatment dilemma, giving patients a glimmer of hope for "functional cure".

So, can this highly anticipated therapy really overturn the old treatment model of T1D?

01 The Clinical Dilemma of 9.15 Million Patients

When we talk about diabetes, the focus in recent years has almost entirely been on the "miracle weight - loss drugs" for type 2 diabetes. Semaglutide quickly became a "phenomenal product" after its launch. Novo Nordisk even restricted the supply due to insufficient production capacity at one point. Eli Lilly's tirzepatide, with its stronger weight - loss effect, triggered a rush for purchase upon its launch, vying for the throne of the new drug king.

This popularity of "consumer - level healthcare" makes the T1D field seem particularly deserted.

However, the lack of attention does not mean the demand is not urgent. According to the 2024 data from the "IDF Global Diabetes Map", there are approximately 9.15 million T1D patients globally, among which nearly 20% (1.81 million) are under 20 years old, and there are 599,000 patients in China.

Different from type 2 diabetes, T1D is caused by the autoimmune destruction of insulin - producing β - cells in the islets. Patients have to rely on exogenous insulin to sustain life from the onset of the disease, and the longer the course of the disease, the more complete the decline of islet function.

Since the discovery of insulin in the 1920s, insulin replacement therapy has been the standard treatment for T1D. Millions of patients need to supplement insulin multiple times a day through insulin pumps or injections. However, even with continuous upgrades of the equipment, the existing treatment methods still cannot solve the core pain points of T1D.

Even with the most advanced insulin pumps and continuous glucose monitoring systems, patients still face two major challenges: Firstly, the risk of hypoglycemia. Approximately 40% of T1D patients experience at least one severe hypoglycemic event each year, which may lead to coma, brain damage, or even death. Secondly, complications caused by long - term hyperglycemia. Among patients with a disease course of more than 20 years, the incidence rates of retinopathy, renal failure, and cardiovascular diseases are as high as 70%, 40%, and 30% respectively.

From a market perspective, the "niche" nature of T1D is only relative. Currently, the average annual treatment cost for global T1D patients is approximately $40,000, and the market size in the United States alone exceeds $8 billion. With the extension of patients' lifespan and the increase in the incidence rate, the rigid demand in this field is continuously expanding.

Therefore, what truly restricts the development of T1D treatment is the technological bottleneck rather than the market scale. Although traditional islet transplantation therapy can achieve insulin independence, it is limited by the shortage of donated organs, and patients need to take immunosuppressants for a long time after transplantation, which further restricts its popularization.

This supply - shortage dilemma has put T1D patients in an awkward situation of "having drugs (insulin) but not being able to cure the disease", leaving a huge breakthrough space for innovative technologies such as stem - cell therapy.

02 The "Terminator" Zimislecel?

The reason why Vertex has caused a stir in the T1D field is that Zimislecel solves the "bottleneck" problem of traditional therapies. It does not rely on donated islets but generates functional islet cells through in - vitro differentiation of stem cells, fundamentally breaking through the limitation of donor shortage.

Starting from induced pluripotent stem cells (iPSCs), through specific molecular induction steps, the stem cells are directionally differentiated into fully mature islet cells, which are then infused into the patient's liver through the hepatic portal vein. After these "artificial islets" are implanted in the liver, they can sense blood - glucose changes like healthy islets and secrete insulin autonomously, thus restoring the patient's blood - glucose regulation mechanism.

Clinical data further verify the subversiveness of this therapy. In the phase 1/2 clinical trial, all 12 patients who received the full - dose (0.8×10⁹ cells) treatment met the standards set by the ADA, with glycated hemoglobin (HbA1c) < 7% and time in the glucose target range (TIR) > 70%. Moreover, 10 of them completely stopped using insulin one year later, with an average daily insulin dose reduction of 92%.

Furthermore, no severe hypoglycemic events occurred in all patients 90 days after treatment, and the level of C - peptide (a core marker reflecting endogenous insulin secretion) in their bodies increased significantly, indicating that the stem - cell - derived islets were successfully implanted and functioning stably.

In terms of safety, neutropenia is the most common serious adverse event. In addition, two patients died. One died of cryptococcal meningitis, and the other died of severe dementia with agitation caused by the progression of pre - existing neurocognitive impairment. Vertex claims that the deaths were not related to the drug.

This means that if the subsequent phase 3 clinical trial is successful, patients will bid farewell to frequent insulin injections. This will undoubtedly subvert the treatment logic of T1D. In the past, the core of treatment was exogenous supplementation, controlling blood glucose through insulin injection or pumping, which was essentially "symptomatic treatment". However, Zimislecel achieves functional replacement by transplanting new islet cells to restore the patient's own insulin - secreting ability, taking a crucial step towards "functional cure".

Vertex stated in its second - quarter earnings conference call that the enrollment and dosing of the pivotal study of Zimislecel are about to be completed. If the data are supportive, it will submit a global application in 2026. Moreover, it emphasized that according to the current clinical data, approximately 60,000 severe T1D patients (with severe hypoglycemia and islet - function failure) in the United States and Europe alone meet the treatment indications for Zimislecel. Overseas analysts predict that if the problem of immunosuppression dependence is solved, its peak sales could exceed $5 billion.

03 The Dawn and Shadows of Cure

Although the clinical data of Zimislecel are encouraging, for Vertex to truly "eliminate" T1D as Gilead did with its miracle hepatitis C drug, it still has several hurdles to overcome.

The biggest drawback is that Zimislecel requires long - term immunosuppressive treatment to prevent the rejection of transplanted cells. Although Vertex uses a glucocorticoid - free immunosuppressive regimen, patients still need to take immunosuppressants for a long time, which weakens the immune system and makes them more vulnerable to immune - system diseases and cancer.

This limitation directly affects the applicable scope and long - term safety of the therapy. For many patients, the risks associated with long - term immunosuppression may be no less than the disease itself.

To solve this problem, Vertex is trying different strategies to "disguise" Zimislecel cells to avoid immune - system attacks, including improving the immunosuppressive regimen, using gene editing to produce low - immunogenicity islet cells, and developing new immune - protection technologies for cell encapsulation.

Unfortunately, in March this year, the phase 1/2 clinical trial of VX - 264 (which aims to develop encapsulation technology to wrap islet cells and isolate them from immune - system attacks, thus avoiding the use of immunosuppressants) was terminated due to failure to meet the expected efficacy. The gene - editing approach is still in the pre - clinical stage and is difficult to implement in the short term.

Of course, Zimislecel is just the vanguard in the "functional cure" field of T1D. Currently, many pharmaceutical companies around the world have laid out in this field. For example, CTX211 of CRISPR Therapeutics uses gene - editing technology to modify stem - cell - derived islet cells, knocking out the HLA gene to avoid immune rejection, and it has now entered the phase 1/2 clinical trial.

OPF - 310 of Otsuka attempts the xenotransplantation approach, transplanting processed pig islet cells into the human body to solve the problem of donor shortage, and it has also entered the phase 1/2 clinical trial.

Clinical exploration is also accelerating in China. The "Allogeneic Human Regenerative Islet Injection" developed by the team of Professor Yin Hao from Shanghai Changzheng Hospital obtained the clinical - trial approval in April 2025, becoming the second allogeneic universal regenerative islet product in the world to enter the clinical - trial stage after Zimislecel.

In addition to allogeneic stem - cell therapy, another approach is to use "autologous stem cells". Its advantage is that it can avoid rejection reactions, but the drawback is also obvious. It requires real - time collection and preparation of the patient's autologous stem cells, resulting in relatively high costs.

Since the discovery of insulin to the present, the treatment of type 1 diabetes has gone through a century - long journey. In the past, patients faced the fate of lifelong injections. Whether Vertex can overturn the old treatment model of type 1 diabetes depends on the subsequent clinical trials and technological iterations. But at least now, the 9.15 million patients have finally seen the dawn of hope.

More importantly, in the future, with the solution of the immune - rejection problem, "functional cure" may become the norm, truly changing the fate of patients.

This article is from the WeChat official account "Amino Observation" (ID: anjiguancha), author: Amino Jun, published by 36Kr with authorization.