After the trailblazing approval of Sanofi’s Tzield for stage 3 type 1 diabetes, several companies, including SAB Biotherapeutics and Eledon Pharmaceuticals, are vying for a spot in the landscape with innovative approaches—and experts say there’s room for all of them.
Type 1 diabetes is a disease with many faces, giving way to a diverse set of innovative approaches with a common goal among them: insulin independence for patients who have long required daily injections to control the autoimmune condition.
Biopharma companies are closing in on several modalities that could change the way type 1 diabetes (T1D) is treated, from therapies that allow patients freedom from near-constant vigilance to preventive measures that could slow or even halt progression.
The field has come a long way over the course of the last few decades, Michael Haller, professor and chief of pediatric endocrinology at the University of Florida, told BioSpace. Haller has worked professionally in the field for more than 20 years and serves as chair of the NIH-funded type 1 diabetes research network TrialNet. But his personal journey with the disease goes back even further.
“My grandfather had type 1, so I have early childhood memories of the time when just staying out of severe hypoglycemia and hyperglycemic crisis was considered doing well,” Haller said. “To be where we are now from the treatment side of things is remarkable progress.”
Since the discovery of insulin in 1921, continuous glucose monitors and automated delivery systems have made this treatment far less cumbersome. But Haller looks to a point on the horizon “where we’re meaningfully and more durably delaying the disease for a larger number of people than we are now.”
Last month’s expanded approval of Sanofi’s Tzield as the first disease-modifying therapy for pediatric patients with stage 3 type 1 diabetes—the stage at which clinical symptoms appear and a diagnosis is made—is the tip of the spear, according to Haller. Tzield could pave the way for a series of pipeline prospects that offer a wave of new options, he added.
“We’re at the end of the beginning,” Haller said, indicating the close of a long first chapter of solely insulin-based treatments. “The approval of a disease-modifying therapy like [Tzield], and hopefully now these other drugs in the pipeline can achieve a similar regulatory approval process and allow us to use personalized approaches to figure out which therapies are going to work best for individual patients.”
A multi-pronged pipeline
Progress in disease-modifying therapies for type 1 diabetes isn’t an isolated effort. Different stages of the disease require a varied approach, scattering the R&D pipeline over a number of biotechs seeking an individual corner of the market.
In addition to companies like SAB and Eledon, Bodnar noted several biotechs looking at different approaches, such as insulin-adjunct therapies from vTv Therapeutics and stem cell approaches like those from Sana Biotechnology and Century Therapeutics.
“The treatment landscape has broken up into different segments, from the preventative setting to the diagnosed patient population, and more recently in the curative type of treatments that can potentially play a role,” said Emily Bodnar, director and senior healthcare analyst at H.C. Wainwright. “All of these companies occupy a different part of that landscape, and innovation in the field is growing significantly.”
Type 1 diabetes, unlike its type 2 counterpart, is an autoimmune disease in which a patient’s own antibodies attack the beta cells of the pancreas, blocking the production of insulin, which controls levels of glucose in the blood. High blood sugar can damage blood vessels and nerves while low blood sugar can cause dizziness and fainting. The disease is progressive, and some companies, including SAB Biotherapeutics, are trying to keep patients from advancing to the later stages of disease with drugs that adjust the immune system to preserve beta cells.
SAB’s lead drug candidate, SAB-142, combines the broad tolerability of a human antibody with the disease-targeting effectiveness of an animal-derived antibody, SAB CEO Sam Reich told BioSpace. The candidate is a human version of the rabbit antibody thymoglobulin, which has been used historically as an immunosuppressant but comes with severe side effects in its animal form.
In an early-stage study, healthy volunteers receiving SAB-142 did not show signs of serum sickness, a common side effect of animal-derived antibodies. And in a small cohort of patients newly diagnosed with T1D, the drug preserved C-peptide and led to better glycemic control, according to Reich.
Reich looks to Sanofi’s Tzield as a “trailblazer” in the field of disease-modifying therapies and believes SAB-142 could offer a welcome addition to the treatment landscape.
“It’s great Tzield was approved. It’s great for patients and it’s great for us, because they led the way in how to study a drug,” Reich said. “But where Tzield bought the patient two years before they became stage 3, if our drug works, we may be able to extend that two years indefinitely with infusions twice a year, and no insulin.”
Reich called SAB-142 a potential “functional cure.” The company has embarked on a Phase 2b pivotal trial in patients newly diagnosed with stage 3 T1D.
Many of the advances in type 1 diabetes, including Sanofi’s Tzield and SAB-142, have come out of the NIH-funded trial network TrialNet, which is chaired by Haller.
On the other end of the R&D spectrum for T1D is Eledon Pharmaceuticals, which is developing tegoprubart for patients who have undergone cellular transplant surgery and have already progressed to later stages of the disease.
In an investigator-initiated trial, the anti-CD40L antibody led to insulin independence in all 12 patients in the study after eight to 22 months of follow-up. The participants had undergone islet cell transplantation, which introduces donated pancreatic insulin-creating cells into the patient’s liver, allowing them to make their own insulin.
“Our drug is a very targeted drug, and so as a result, we don’t have a lot of the side effects you see with older drugs, including the standard-of-care tacrolimus,” CEO David-Alexandre Gros told BioSpace, referring to the immunosuppressive drug used in allogenic organ transplant. “These are people that haven’t been able to control their diabetes for a very long time, and in four weeks after they get the transplant, they were able to get to good glycemic control and every one of the patients got off insulin.”
There will always be room for myriad approaches to T1D, Bodnar said. “What’s interesting about the different segments is you’re going to have patients in all of them, no matter what.”
The long road
While new treatments and “functional cures” like SAB’s and Eledon’s candidates may potentially fulfill the promise of insulin independence, other companies are on the path to longer-term options. But they aren’t on the immediate horizon, Bodnar said.
“The key innovation patients and physicians are hoping for is a therapy that doesn’t require immunosuppression,” she added. “But that’s a long way down the road.”
Last year, a stem cell-derived therapy from Vertex Pharmaceuticals called zimislecel demonstrated in a Phase 1/2 trial that 83% of patients with type 1 diabetes no longer required injected insulin a year after a single infusion of the drug.
Others like Sana Biotechnology are developing gene-modified islet cells that wouldn’t require immunosuppression and could potentially lead to insulin independence. The company showed in a first-in-human study in March that the cells were safe and continued to produce insulin after 14 months. Sana plans to begin a Phase 1 trial as early as this year.
Even a successful gene therapy wouldn’t fully corner the market and forestall competition, Bodnar noted. Genetic treatments for diseases like sickle cell or beta thalassemia only penetrate about 10% to 20% of their respective patient populations, she said, and T1D will likely follow that playbook.
GLP-1 drugs have opened an enormously lucrative and effective market for pharma giants Eli Lilly and Novo Nordisk in type 2 diabetes and obesity. The diseases themselves vary greatly from T1D, but there’s still some overlap in the patient population that could give rise to combination treatments, Bodnar said.
About one in four patients with T1D also have type 2, she pointed out, making combination studies worth looking into in the same way that GLP-1s have been integrated into early combo trials in areas like neurodegenerative diseases and substance use disorders.
However, the comparatively small size of the type 1 diabetes population next to GLP-1s’ primary populations might not have industry behemoths like Novo and Lilly prioritizing studies on the basis of market potential, Bodnar said.
