Breakthrough T1D joined thousands within the diabetes community at the American Diabetes Association’s (ADA) 83rd Scientific Sessions, where hundreds of experts presented significant advancements in diabetes research that may prove to be pivotal in improving lives and finding cures for T1D.
Held June 23-26 in San Diego, the ADA Scientific Sessions is one of the most prominent opportunities for researchers, healthcare professionals, and industry members to learn about the latest in diabetes research, treatment, and care. JDRF-supported research has been highlighted at the annual event since Breakthrough T1D started funding research nearly 50 years ago. This year, scientists presented 140+ studies—with Breakthrough T1D-funding at present or in the past—to encompass breakthrough clinical trials and significant research studies that are paving the way to novel treatments and technologies for T1D.
The ADA Standards of Care for Diabetes has been updated to include Tzield™ (teplizumab-mzwv) to delay T1D in at-risk individuals. Read more about Breakthrough T1D’s work—funding discovery research to clinical development to work with regulators—that brought Tzield to FDA approval.
There were many fantastic results that came through the ADA’s Scientific Sessions. Here is Aaron J. Kowalski, Ph.D., CEO of Breakthrough T1D, with the key takeaways from the conference, and there is a written summary of Breakthrough T1D highlights below.
Cures
Stem Cell-Derived Islet Replacement Therapy: Update on Vertex’s VX-880
Breakthrough T1D Research Area: Cell Therapies
Cell replacement therapies, including stem cell-derived islet therapy, were on fire, with Vertex Pharmaceuticals leading the way in clinical trials. Vertex launched its clinical trial of VX-880, a stem cell-derived islet therapy in T1D for individuals with hypoglycemia unawareness, in combination with immunosuppressive therapy to protect the cells from rejection, in the summer of 2021. To date, six participants have received this therapy, and two are now insulin independent, have met the primary endpoint of eliminating severe hypoglycemia events, and have exceeded the ADA target time-in-range (>70%). Based on these data, the phase I/II study advanced to Part C in full target dose.
In summary: VX-880 has the potential to achieve insulin independence, as well as eliminate severe low blood-sugar events and significantly improve blood-sugar control.
Breakthrough T1D Leadership: Vertex’s phase I/II clinical trial of VX-880 was pioneered by Doug Melton, Ph.D., whose years of JDRF-funded research led to successfully transforming stem cells into beta cells in 2014, and a catalytic investment from the T1D Fund in Semma Therapeutics—a biotech company founded by Melton to develop a stem cell-derived islet therapy for T1D, which was acquired by Vertex Pharmaceuticals.
Islet Replacement Therapy: Update on Sernova “Cell Pouch” Therapy
Breakthrough T1D Research Area: Cell Therapies
Breakthrough T1D also heard from Sernova, who provided an update on the phase I/II clinical trial of their Cell Pouch™—an implantable device designed to form a natural environment and allow the survival and function of insulin-producing (islet) cells. This device uses islets from deceased donors. In the first cohort, six individuals have received the therapy, and five have remained insulin independent, going from 6 months to more than 3 years. Observations from the first cohort led to a higher-capacity Cell Pouch, which provides up to 56% more volume to accommodate more islets, and 5 of the 7 planned participants have been enrolled in the second cohort.
Breakthrough T1D continues to support Sernova to make their Cell Pouch part of the cures portfolio.
TYK2 Inhibitors: Not for Psoriasis Anymore
Breakthrough T1D Research Area: Disease-Modifying Therapies
TYK2 is a crucial signaling pathway that has a role in autoimmune diseases, including psoriasis, Crohn’s disease, and lupus. Moreover, a TYK2 inhibitor—which works by blocking the TYK2 protein and the inflammation that it brings—was FDA-approved in September 2022 for moderate-to-severe psoriasis. But, researchers asked, would a TYK2 inhibitor have similar effects on the development of T1D?
The study showed that a TYK2 inhibitor reduced diabetes incidence by up to 80%, decreasing the immune cells that cause T1D and increasing the immune cells that signal tolerance. Taken together, their findings demonstrate that TYK2 inhibition protects against beta cell stress and T1D development, in multiple preclinical models.
Breakthrough T1D Leadership: The results were presented by Breakthrough T1D-funded researcher Farooq Syed, Ph.D., who was a Breakthrough T1D fellow working with Breakthrough T1D grantee Raghu Mirmira, M.D., Ph.D., the ADA’s 2023 Albert Renold Award recipient. Co-authors on the abstract are Breakthrough T1D-funded researchers Decio Eizirik, M.D., Ph.D. and Carmella Evans-Molina, M.D., Ph.D.—ADA’s 2023 Outstanding Scientific Achievement Award recipient.
General Population Screening: It’s Time
Breakthrough T1D Research Area: Screening and Monitoring
An ADA/Breakthrough T1D symposium, moderated by Sanjoy Dutta, Ph.D., chief scientific officer at Breakthrough T1D, featured an update on screening and monitoring in Europe (Fr1da, Diabetes Prediction and Prevention (DIPP) Study) and the United States (Autoimmunity Screening for Kids, or ASK), which are now expanding globally. The session highlighted the progress we have made, such as the benefits of screenings, including a decrease in DKA at diagnosis and lower HbA1c levels versus children who had not been screened. The gaps to move general population screening into state and federal guidelines: Cost-effectiveness of screening, at what age(s) do you screen, and how do you monitor when a person has 2+ autoantibodies. Research in all of these is under way.
2+ autoantibodies—antibodies that are directed toward your own body—means you have an almost 100% chance of developing T1D in your lifetime.
Breakthrough T1D Leadership: As a result of decades of Breakthrough T1D-funded research, we can identify those at highest risk for developing T1D—2+ autoantibodies—and we have funded screening programs since they were first introduced in the late 1980s. More recently, Breakthrough T1D launched the T1Detect screening education and monitoring program to broaden screening awareness and access to the general population. The goal: Global universal screening, which is key to developing disease-modifying therapies—like Tzield™ (teplizumab-mzwv), FDA-approved to delay T1D in at-risk individuals—and, ultimately, preventing it entirely.
Improving Lives
Lower Your HbA1c Levels + Reduce Insulin Use ≠ DKA = Success!
Breakthrough T1D Research Area: Glucose Control
SGLT therapies can lower HbA1c levels but increase the risk of diabetic ketoacidosis (DKA). So far, they are only approved for type 2 diabetes. But what if you combined an SGLT therapy with another drug that could improve blood-sugar levels AND potentially reduce ketones? A JDRF-funded phase I/II clinical trial wanted to find out if this combo could work for people with T1D. The results? Pretty amazing.
Diabetic ketoacidosis (DKA)—a life-threatening complication, typically resulting from not enough insulin in the body—is an abundance of ketones in the blood, which typically also happens when blood sugar is very high. With SGLT therapy, however, DKA presents with blood-sugar levels at normal or near it. Because of this, there will be a need to counteract the risk if SGLT is going to be approved for T1D.
The combination therapy of an SGLT inhibitor (dapagliflozin) and a glucagon receptor inhibitor (volagidemab) reduced average blood sugars, reduced total insulin use, and increased time-in-range (by >3.8 hours a day!), and there was no DKA or severe low blood sugar. This led Schafer Boeder, M.D., presenter on the clinical trial, to conclude: “This therapeutic combination has the potential to improve glycemic control and reduce insulin use, while mitigating ketogenesis in T1D.”
Breakthrough T1D Leadership: This study involved numerous Breakthrough T1D-funded researchers: Dr. Boeder, as well as Jeremy Pettus, M.D., and Justin Gregory, M.D.—two of his authors on the abstract.
Breakthrough T1D is now funding REMD Biotherapeutics, to run a clinical trial investigating the impact of volagidemab on rescue glucagon to treat severe low blood-sugar events.
“I literally wouldn’t be here doing what I’m doing if I didn’t have funding from Breakthrough T1D. I feel like I’m making a difference, and that’s huge. So having this funding has allowed me to focus on exactly what I want to do and keep doing it thanks to their support.”
– Jeremy Pettus, M.D.
Endocrinologist and Assistant Professor of Medicine
University of California, San Diego
Technology Updates
Breakthrough T1D Research Area: Artificial Pancreas / CGMs
A ton of presentations focused on the artificial pancreas, or automated insulin delivery (AID), systems and continuous glucose monitors (CGMs). Real-world results on two artificial pancreas systems—Omnipod 5 and Medtronic 780G—demonstrated that they significantly improved time-in-range, with averages of 69% and 70% for Omnipod 5 (using the most aggressive target, internationally and in the United States) and 80% and 86% for the Medtronic 780G (for all of the United States users and those with Medtronic’s recommended settings). Time-below-range was 1% for Omnipod 5, and 2.3% for the Medtronic 780G. iLet insulin-only bionic pancreas showed that it improved blood-sugar management independent of how much users interact with the automated insulin delivery (AID) device. And Senseonics presented data from its 365-day implantable CGM, showing that it performed as well as the 180-day sensor.
Breakthrough T1D Leadership: The iLet presentation involved research from several former Breakthrough T1D-funded scientists: Ed Damiano, Ph.D., CEO of Beta Bionics; Firas El-Khatib, Ph.D., co-founder and vice president, research & innovation, at Beta Bionics; and Steven Russell, M.D., Ph.D.
The First Study to Show Correlation Between Time-in-Range and Complications
Breakthrough T1D Research Area: Complications
Continuous glucose monitoring (CGM) metrics, such as time-in-range, have been proposed as new metrics to assess diabetes management. No longitudinal studies, however, have placed time-in-range and diabetic eye disease…until now.
Viral N. Shah, M.D., in a study funded by Breakthrough T1D, analyzed up to 7 years of retrospective CGM data; 92 of people were without a diagnosis of diabetic eye disease and 71 of them were. HbA1c of the diabetic eye disease was significantly higher than those without a diagnosis. But people with diabetic eye disease had an average time-in-range of 52%, while the control group had a time-in-range of 62%—meaning that every 5% point decrease in time-in-range was associated with a 16% risk increase in diabetic eye disease. Time-in-tight target range (70-140 mg/dL) and time above range (>180 mg/dL) were also associated with the disease.
What does this mean? 1. It’s the first longitudinal study to demonstrate the association between CGM metrics and complications. 2: Time-in-range could become closer to realizing its potential application in T1D management and clinical trials.
Breakthrough T1D Leadership: Dr. Shah is an important part of the University of Colorado-JDRF-scientist atmosphere, which goes back to the 1980s. From George Eisenbarth, M.D., Ph.D., who came up with the staging system in 1986, and Kevin Lafferty, Ph.D., who had demonstrated that a second signal is required to activate immune cells, to the next generation of researchers. Co-authors of the abstract include Gregory Forlenza, M.D., who is an expert on artificial pancreas systems in youth, Sarit Polsky, M.D., MPH, a specialist in T1D and pregnancy, and Halis Akturk, M.D., an authority on checkpoint—the “brakes” of the immune system—inhibitor-induced T1D.
We also had the opportunity to hear about the Mary Tyler Moore Vision Initiative (MTM Vision), with S. Robert Levine, M.D., the husband of the late Mary Tyler Moore and creator of MTM Vision, Jennifer Sun, M.D., MPH, and Patrice Fort, M.S., Ph.D. The first part of this initiative is a new Diabetic Retinal Disease Staging System, to update the grading system that has not been changed for 50 years, despite the advancement of our understanding the disease and its presentation.
Dr. Fort is collecting and characterizing different stages of the disease, to do in-depth analysis of those tissues to identify new potential targets to be developed. Dr. Sun presented work to identify new clinical endpoints and biomarkers for better characterization of the progression of the disease. She is spearheading clinical trials that will take place at the beginning of next year.
Breakthrough T1D Leadership: Breakthrough T1D has supported eye disease research since its beginning, and has driven discoveries that have reduced the risk of blindness by 95%, including laser therapy and anti-VEGF treatments. In 2018, Breakthrough T1D and the Mary Tyler Moore and S. Robert Levine, MD, Foundation launched MTM Vision, an ambitious initiative to reverse diabetes-related blindness and vision-threatening eye disease, which afflicts millions of individuals worldwide, held in honor of Mary Tyler Moore’s contributions to diabetes awareness and research.
Novel Interventions for the Most Vulnerable
Breakthrough T1D Research Area: Psychosocial
Many Breakthrough T1D-funded researchers presented on psychosocial issues, including the stigma associated with diabetes, telehealth and diabetes distress, depression, and anxiety, and social inequities—economically vulnerable, minorities, food insecurity—in diabetes care, including Michael Harris, Ph.D., whose Novel Interventions in Children’s Healthcare (NICH) was among the winners of the Innovation Challenge.
The inaugural ADA Innovation Challenge was designed to connect diabetes leaders with investors to move the field forward.
Funded by the Helmsley Trust, Breakthrough T1D, and other like-minded organizations, NICH is an innovative program designed to integrate medical care with behavioral therapy to support at-risk youth and their families. It deploys interventionists to address social determinants of health for the most vulnerable, highest need youth with T1D—the 1% who are responsible for 25% of cost. They had fantastic results over the past years, significantly reducing DKA and diabetes-related admissions to the hospital and a drop in HbA1c.
You can view all of the oral and poster presentations on the Diabetes journal website.
