While we look back on 2024, we can reflect upon the incredible progress we’ve made in advancing breakthroughs toward cures and improving everyday life with T1D.
This wouldn’t have been possible without each and every one of you and your continued support of our mission as we drive toward cures for T1D.
Here are the top 11 advances that together, we made happen in 2024:
Breakthrough T1D announced the launch of Project ACT, an initiative aimed at accelerating breakthroughs in T1D cell replacement therapies that do not require broad immunosuppression. Recent advances, such as Vertex’s stem cell-derived islets, have been made possible by Breakthrough T1D’s Cell Therapies program as part of our drive toward cures. The goal of Project ACT is to push research, development, regulatory policies, access, and adoption to increase the rate at which cell therapies without the need for broad immunosuppressants will become available to people with T1D.
Why this matters: Immunosuppressive drugs are a barrier to access to cell replacement therapies because of their toxic side effects, which is why islet transplants are currently only available to people with severe low blood sugar (hypoglycemic) unawareness and episodes. By striving toward a future where we realize the benefits of cell replacement therapies without the downsides of the current regimen of immunosuppressants, we will make islet replacement therapies broadly accessible to the T1D community.
Vertex’s clinical trial of VX-880, a first-generation stem cell-derived islet replacement therapy for people with severe hypoglycemia (requiring the use of immunosuppressants), has transitioned into a phase 1/2/3, or pivotal, trial. This news comes after Vertex shared incredibly promising data in the earlier phases of the trial, including 11 of 12 participants reducing or eliminating the need for external insulin.
The upcoming trial will expand to 50 people who will get a single, target dose of VX-880. The primary endpoint will be insulin therapy independence without severe hypoglycemic events after one year. This is the final clinical testing stage before Vertex can seek FDA approval.
Breakthrough T1D has a decades-long relationship with Vertex and the leading scientists behind stem cell-derived islet therapies, an advancement that would not have been possible without Breakthrough T1D funding and support. The T1D Fund had invested in Semma Therapeutics, which was acquired by Vertex Pharmaceuticals in 2019, eventually leading to the active clinical development of VX-880 in T1D.
Why this matters: This is the first time a scalable cure for T1D is entering phase 3 clinical trials—a significant win and a huge step toward accelerating the delivery of cell therapies to members of the T1D community!
Tegoprubart: Transplant Survival Without Standard Immunosuppressive Drugs
Tegoprubart, an anti-CD40L immunotherapy that limits the immune response, is being tested in a Breakthrough T1D-funded study in people with T1D and severe hypoglycemia who have received deceased donor islets. Eledon Pharmaceuticals announced promising initial results in which two of three people achieved insulin therapy independence. According to the study, tegoprubart is safer for both people and transplanted cells in comparison to broad immunosuppressants, with milder side effects and greater islet survival. To further support this effort, the T1D Fund: A Breakthrough T1D Venture invested in Eledon.
Cell Pouch: A Home for Transplanted Islets
Breakthrough T1D has been supporting the development of Cell Pouch, an implantable device from Sernova that provides a safe, immune-protected environment for transplanted islet cells. In phase 1/2 clinical trials, all six people who received donor islets within the Cell Pouch achieved sustained insulin therapy independence with immunosuppressants, including long-term islet survival and function over five years without harmful side effects.
Why this matters: Standard of care immunosuppressive drugs that help avoid transplant rejection come with unwelcome side effects, such as increased risk of infection and malignancy and toxicity to kidneys, nerves, and islet cells themselves. Breakthrough T1D is focused on finding alternative ways to keep transplanted islet cells alive and healthy so that cell replacement therapies can become more tolerable and accessible.
In a major effort spearheaded by Breakthrough T1D, the first internationally recognized clinical guidelines for those who test positive for T1D autoantibodies have been published. These include guidance on monitoring frequency, education, and psychosocial support in addition to recommended actions for healthcare professionals (HCPs) when the risk of T1D progression is high. The guidelines were cooperatively developed with over 60 international experts spanning ten countries.
Why this matters: Previously, there had been no consensus on monitoring guidelines for people who test positive for T1D autoantibodies. Standardization of clinical recommendations means that individuals, families, and HCPs have tangible next steps to monitor early T1D progression and catch life-threatening complications sooner.
- Breakthrough T1D is leading a campaign to secure a recommendation for T1D screening from the U.S. Preventative Services Task Force (USPSTF), the main authority for preventative care. Approval would require T1D screening to be covered by insurance—an important step forward in expanding access.
- Driven by Breakthrough T1D’s advocacy efforts, The Centers for Medicare and Medicaid Services (CMS) established a unique ICD-10 code for stage 2 T1D. ICD-10 codes are used by HCPs to classify and document diagnoses, symptoms, and procedures. These codes provide a unified way for doctors and providers to indicate what diseases or conditions a person has in their electronic health record (EHR), empowering HCPs to document accurate diagnoses and provide the best possible care.
Why this matters: T1D early detection is critically important to prevent life-threatening complications at diagnosis and to give people necessary resources to make informed decisions about their health. Integrating T1D screening into the U.S. healthcare system will increase access to care.
The past year has seen some important advances in glucose management therapies and devices:
- Cadisegliatin, an activator of a blood sugar regulator in the liver, is being investigated in a phase 3 clinical trial (TTP399) as an adjunct therapy to insulin for people with T1D, although it is currently placed on clinical hold. vTv Therapeutics, the trial sponsor, is also a T1D portfolio company.
- The Omnipod 5 app is now available for the iPhone, making it easier to control the Omnipod without the need to carry a controller. It can also integrate with the Dexcom G6 continuous glucose monitor (CGM).
- Eversense 365 is the first FDA-approved year-round sensor that can easily integrate with automated insulin delivery (AID) systems. Other sensors require replacement after 10-14 days.
Why this matters: While advancements in glucose management have been pivotal in improving health outcomes for people with T1D, access remains a challenge. AID systems are globally underutilized, and not everyone has the necessary technology to connect devices. Breakthrough T1D is working to not only support advances in glucose management but also increase access.
Related content: While Breakthrough T1D consistently strives to improve the lives of those living with T1D, as an organization we have made incredible progress in the development of AID systems, also called the artificial pancreas systems. Read a historical perspective written by Breakthrough T1D volunteer Doug Lowenstein that covers conception to FDA approval of the first artificial pancreas systems, which changed the lives of people with T1D.
An inquiry spearheaded by the Breakthrough T1D affiliates in the U.K. uncovered risks of developing T1D eating disorders (T1DE), including bulimia, anorexia, or insulin restriction to lose weight. There is a significant gap in education and clinical guidelines for HCPs, a lack of internationally recognized criteria for T1DE diagnosis, and insufficient care integration, leading to preventable complications and healthy years of life lost. Breakthrough T1D recognizes the importance of spreading awareness and support for T1DE, and much work is needed to improve the lives of those living with T1DE.
Why this matters: There is an urgent need to change the way T1DE is approached, including integrated physical care with mental health services to get people with T1DE the access to care that they need.
In a study that included people with T1D, finerenone (Kerendia®) has been shown to improve cardiovascular outcomes in adults with heart failure. The drug is already approved in the U.S. to treat kidney and cardiovascular disease in people with T2D. Based on these results, Breakthrough T1D is supporting a clinical trial (FINE-ONE) in conjunction with Bayer to investigate the use of finerenone for T1D with the hopes of reducing kidney complications.
Why this matters: Kidney and cardiovascular disease remain significant challenges for those with T1D, especially given the FDA’s recent rejection of an SGLT inhibitor to lower blood glucose in people with T1D and chronic kidney disease. Yet, a new clinical trial (SUGARNSALT) will better assess the benefits versus risks.
Breakthrough T1D is advocating for the regulatory approval of C-peptide, a biomarker for insulin production by beta cells, to be used as an endpoint in clinical trials. An endpoint can accurately predict a meaningful benefit in clinical trials for disease-modifying therapies (DMTs; treatments that can slow, halt, or reverse T1D). To support this endeavor, Breakthrough T1D scientists and an expert consensus panel published research with evidence supporting C-peptide as an endpoint. Breakthrough T1D is continuing to engage with regulators, coordinate with industry, and assess more clinical trial data to drive this effort forward.
Why this matters: Current clinical trial endpoints (HbA1c, hypoglycemia, and complications) are not the best way to gauge the clinical benefits of T1D therapies. If C-peptide gets regulatory approval to be used as an endpoint, clinical trials could be smaller and shorter while still accurately assessing the advantages of a DMT. This means that drug development can move more quickly, and people with T1D will be able to access therapies sooner.
Related content: Two years ago, the T1D community received the incredible news that Tzield® had become the first FDA-approved disease-modifying therapy that can significantly delay T1D onset. Breakthrough T1D volunteer Doug Lowenstein recounts the life-changing drug’s journey nearly 100 years after the discovery of insulin.
The T1D Index is a data simulation tool that measures the global health impact of T1D, bridging gaps in our knowledge of public health statistics. T1D Index 2.0 has new and improved functionality, including advanced simulation capabilities, validation of data, and enhanced user experience. Breakthrough T1D contributed to both the development and improvement of the T1D Index.
Why this matters: The T1D index is critical in defining the intercontinental scope of T1D, driving us toward country-specific solutions and improved global health outcomes.
Earlier this year, JDRF rebranded to Breakthrough T1D. While our mission remains the same, our name needs to better reflect who we are and where we’re going. Our new brand aligns with our mission to accelerate life-changing breakthroughs for those of every age living with T1D as we work toward a world without it.
Why this matters: The proof is in the name—each day we strive to increase and accelerate breakthroughs in T1D, and it’s critical for our brand to accurately reflect our mission.
It’s certainly been an exciting year! While we still have more work to do, it’s crucial to celebrate our wins, both big and small, to see how far we’ve come in our push to make T1D a thing of the past.
Together, we’re accelerating breakthroughs for people with T1D, and the support of the T1D community drives our mission forward every single day, leading the way to lifechanging therapies and cures. Let’s see what 2025 has in store!
In the past year, we’ve seen a turning point for type 1 diabetes (T1D) treatments and technologies. In improving lives, we have new artificial pancreas systems and continuous glucose monitors (CGMs), which make living with T1D more manageable and convenient. In the area of cures for T1D, we have—in a historic moment for T1D—the first disease-modifying therapy, Tzield (teplizumab-mzwv), for use in delaying the onset of clinical disease in at-risk individuals.*
But what about the approximately 60,000+ people in the United States who are diagnosed each year with new-onset T1D?
Results from a new clinical trial suggest that Tzield has the potential to slow the progression of T1D for them.
Presented by Kevan Herold, M.D., and published in the New England Journal of Medicine, the PROTECT clinical trial investigated whether Tzield can slow the loss of beta cells and preserve beta cell function as measured by C-peptide in newly diagnosed (stage 3 T1D) children and adolescents ages 8-17. Per the study results just announced, it can.
In a press release issued by Sanofi (who acquired Provention Bio in April 2023), the data showed that:
- Tzield met the study’s primary endpoint, significantly slowing the decline of C-peptide levels, compared to placebo
- C-peptide is a biomarker for beta cell function
- Numerical trends favoring Tzield were seen in key secondary endpoints, whilst statistical significance was not achieved
- On average, people on Tzield required numerically fewer insulin units and had numerically higher time in range, compared to those on placebo
- Tzield has the potential to slow the progression of Stage 3 T1D in newly diagnosed individuals
“Tzield demonstrating effectiveness in a study of newly diagnosed children and adolescents is outstanding news,” said Sanjoy Dutta, Ph.D., Breakthrough T1D chief scientific officer. “Preserving beta cell function in individuals diagnosed with type 1 diabetes is a critical step towards cures and, crucially, is helpful in type 1 diabetes management in these people. Breakthrough T1D has believed in this therapy for decades and is continuing to study its potential uses in type 1 diabetes.”
“Thanks to Provention Bio and Sanofi’s ongoing commitment and dedication to individuals with type 1 diabetes, we now know that Tzield can benefit a new subset of the T1D population. Breakthrough T1D applauds all efforts aimed at finding cures and improving therapies for individuals with type 1 diabetes.”
Tzield is not yet FDA approved for individuals with stage 3 T1D. In Sanofi’s press release they say that they look forward to discussing this new data with the scientific community and regulatory authorities around the world.
Breakthrough T1D has supported the development of teplizumab for nearly 30 years, which includes contributions through research grants, federal funding via the Special Diabetes Program, a strategic investment by the Breakthrough T1D T1D Fund that brought Provention Bio into T1D for the first time, and more.
Breakthrough T1D is also currently pursuing multiple therapeutic approaches to cure T1D, and the T1D Fund has over 20 active cures programs in development.
*At-risk, or stage 2 T1D, means that a person exhibited 2+ T1D-related autoantibodies—antibodies against one’s own self—and their blood glucose is starting to be abnormal, but they are not yet insulin dependent. When someone becomes insulin dependent, they are in stage 3 T1D.
JDRF’s vision is a world without type 1 diabetes (T1D) and in the past fiscal year, through many top type 1 diabetes advances, we’ve made incredible progress toward that goal.
Your support of our efforts is inseparable from the top type 1 diabetes advances we’ve seen in accelerating cures, improving lives, and advocacy wins for people with T1D and their loved ones.
As we approach the end of fiscal year 2023 (FY23), let’s highlight the many top type 1 diabetes advances we’ve seen.
Top Type 1 Diabetes Advance 1: First T1D Disease-Modifying Therapy
In a historic moment for T1D—and one that Breakthrough T1D had a hand in from the beginning, supporting research from the 1980s on—the U.S. Food and Drug Administration (FDA) approved Tzield™ (teplizumab-mzwv) for use in delaying the onset of clinical disease in at-risk individuals aged 8+.
For the first time in history, Tzield will treat the autoimmune process behind T1D, not the symptoms, altering the course of the disease.
Among our top type 1 diabetes advances, this is the first disease-modifying therapy—treatments that can slow, halt, or reverse the course of the disease—for T1D to be approved, but it won’t be the last.
Additionally, months after Tzield’s FDA approval, Sanofi acquired Provention Bio, the manufacturer of Tzield.
The acquisition brings the first T1D disease-modifying therapy available in the U.S. into the portfolio of a global leading pharmaceutical company, representing an endorsement of the potential of these types of therapies and, we hope, the opportunity to bring this life-changing therapy and others in the pipeline to more people faster.
Tzield and breakthroughs like it put us on the pathway to finding cures and, one day, preventing T1D entirely.
Top Type 1 Diabetes Advance 2: A Blood Pressure Drug Preserves Beta Cell Function
A Breakthrough T1D-funded study found that children and teens newly diagnosed with T1D who took verapamil—a drug already approved to treat high blood pressure—were making more insulin one year after diagnosis than those on placebo. In other words, in the children and teens who took verapamil, more beta cells were healthier one year post T1D diagnosis than those in the children and teens who took the placebo.
This was the second trial that found the drug can preserve beta cells in the newly onset period.
Additional studies may be needed to further validate the results, as well as identify all benefits and potential side effects of the drug. Breakthrough T1D has the strategy to answer these and other questions.
The finding brings us closer to our goal of having numerous disease-modifying therapies widely available for people with type 1 diabetes.
Top Type 1 Diabetes Advance 3: Affordable Insulins for Everyone
Breakthrough T1D and partnering organizations are supporting nonprofit pharmaceutical manufacturer Civica Rx to produce biosimilar insulin that will cost no more than $30 a vial/$55 a box of five pens, regardless of insurance status.
One year after the Civica announcement, Eli Lilly, Novo Nordisk, and Sanofi all announced reductions to the prices of their insulins—including the most used insulins, such as Humalog, NovoLog, and Lantus.
Another big win for insulin affordability was the $35 monthly out-of-pocket co-pay cap for those on Medicare included in the Inflation Reduction Act that Breakthrough T1D fought hard to secure.
In April, the Senate Diabetes Caucus Co-Chairs, Jeanne Shaheen (D-NH) and Susan Collins (R-ME), introduced the INSULIN Act of 2023, another key step toward achieving affordable insulin for all who need it.
The bill seeks to limit out-of-pocket insulin costs by ensuring that people with commercial insurance pay no more than $35 or 25 percent of the net price per month for at least one insulin of each type and dosage form, and includes other important provisions to help make insulin more affordable and accessible.
You can contact your members of Congress and encourage them to support the INSULIN Act of 2023.
Top Type 1 Diabetes Advance 4: Turbo Boosting Cell Therapies
Breakthrough T1D is working to develop and deliver life-changing therapies that place healthy, insulin-producing beta cells back into the bodies of people with T1D. There was a lot of progress in FY23.
Vertex, which previously acquired Semma Therapeutics, also acquired ViaCyte, bringing together the leading companies developing stem cell-based therapies for diabetes.
Vertex is advancing a stem cell-derived islet replacement therapy for T1D. It’s in human clinical trials and showing amazing results, with one participant being off insulin entirely.
Vertex also started a trial with a new product using encapsulated stem cell-derived islets as replacement therapy, and is exploring gene-edited stem cell-based therapies—both with the goal of eliminating the need for immunosuppressive drugs.
Just this past April, Aspect Biosystems—an industry leader in 3D bioprinting technology—and Novo Nordisk announced a partnership to expand the development of a new class of treatments for diabetes and obesity, using Aspect’s bioprinting technology and Novo Nordisk’s expertise in stem cell and cell therapy development.
The Aspect-Novo Nordisk partnership’s initial focus will be on developing bioprinted therapies for transplant that would be designed to maintain normal blood-sugar levels without the need for immunosuppression. This could represent a transformative treatment for people living with T1D.
Additionally, the U.S. Food and Drug Administration (FDA) approved CellTrans’s Lantidra™, the first cell therapy to be authorized in the United States, for use in adults unable to approach average blood glucose levels due to current, repeated episodes of severe low blood sugar. This therapy, which requires the use of immunosuppressive drugs, takes deceased donor islets and places them into people with T1D suffering from repeated severe low blood-sugar, called hypoglycemia, events. This is an exciting first.
Approved! Numerous T1D Management Technologies
Breakthrough T1D funds research to facilitate the development of new therapies and technologies to make day-to-day life with T1D easier, safer, and healthier. In the past year, we saw:
Newly-Approved Artificial Pancreas (AP) Systems and Algorithms
- iLet® Insulin-Only Bionic Pancreas System for ages 6+
- Medtronic MiniMed™ 780G AP system for ages 7+
- Tidepool Loop, an algorithm that will allow for interoperability of continuous glucose monitors (CGMs) and insulin pumps
Newly-Approved Continuous Glucose Monitoring (CGM) Systems
- Dexcom G7® CGM system for ages 2+
A New Tool to Accurately Diagnose Type 1 in Adults
Misdiagnosing adults with T1D as having T2D is an all-too-common problem that can have tragic consequences. Breakthrough T1D and IQVIA teamed up to develop an algorithm using artificial intelligence to examine medical records and identify individuals who were diagnosed with T2D but actually have T1D. This could be used in real time to correct misdiagnoses, offering the potential for future development into a clinical decision support tool.
A First-of-its-Kind Lifesaving Tool: The T1D Index
Breakthrough T1D and other T1D-related organizations launched the T1D Index, a first-of-its-kind data simulation tool that offers the most accurate estimate of T1D ever created. The Index measures and maps how many people live with this condition in every country, the healthy years of life it takes from people living with T1D, the number of people who would still be alive today if they hadn’t died prematurely from T1D complications, and our global strategy to reduce the impact of T1D.
Go Forward
Your partnership has been crucial to these advances and many more. On behalf of our community, thank you for moving us forward and ever closer to a world without T1D.
We are excited for the top type 1 diabetes advances that fiscal year 2024 (FY24) will bring!
Read Past Blogs about Top Type 1 Diabetes Advances:
What We Can Be Proud of in 2022
What We Can Be Proud Of in 2020
Top 10 T1D Breakthroughs of 2019
Breakthrough T1D is funding work on multiple ways to delay or prevent the onset of type 1 diabetes (T1D), and Breakthrough T1D-funded researchers may have found a clue.
A publication with lead author Kacey Prentice, Ph.D., and her colleagues in the Hotamisligil Lab at the Sabri Ülker Center of Harvard T.H. Chan School of Public Health, has found that targeting a new hormone complex can enhance beta cell function and prevent T1D. The FABP4 and nucleoside kinase complex, labeled Fabkin, could be a promising therapeutic target, according to the researchers, as it is found at high levels in people with T1D, and targeting it preserves beta cell function and survival.
“Breakthrough T1D was instrumental in supporting this project. Financially in terms of project grants and my own Postdoctoral Fellowship, as well as building a community of researchers with a common goal,” says Dr. Prentice. “Breakthrough T1D facilitated our connection with clinicians and biobanks, allowing us to gain access to patient samples to provide human relevance for our findings. This diverse community of researchers provides great perspective into all aspects of this disease and gives a greater meaning to our own work—not only to gain understanding of the biological processes, but also actively think about how we can make a real difference in the lives of patients.”
“We a very grateful to Breakthrough T1D, whose goal is not just financial support, but to really home in on identifying an important problem, getting researchers and collaborators to focus on it, and asking ‘How is the project going? Is there anything we can do to tackle these problems?’,” says Gökhan S. Hotamisligil, M.D., Ph.D., JS Simmons Professor and the director of the Sabri Ülker Center for Metabolic Research at Harvard, a senior author of the publication, and a mentor to Dr. Prentice. “In fact, it is through Breakthrough T1D that we were introduced to Dr. Anette-Gabriele Ziegler and colleagues—our valuable collaborators in this study to explore the human relevance of our findings. This should be a model for supporting science to tackle challenging problems.”
Dr. Prentice shares how she and her colleagues hope to make prevention of T1D a possibility sooner rather than later:
Funding prevention research is critical in our mission to find cures for T1D. Please consider donating today, and Breakthrough T1D will help turn type 1 into type none, with your support.
In addition to Drs. Prentice and Hotamisligil, Breakthrough T1D has also given support, either now or in the past, for Peter Achenbach, M.D., Anette-Gabriele Ziegler, M.D., and Feyza Engin, Ph.D.
Citation: Prentice, K.J., Saksi, J., Robertson, L.T. et al. A hormone complex of FABP4 and nucleoside kinases regulates islet function. Nature (2021). https://doi.org/10.1038/s41586-021-04137-3
Wouldn’t it be nice if you could take a vaccine as a child—like you do for mumps, polio, and measles—and type 1 diabetes (T1D) would not develop? This could be a real option for families in the not-too-distant future.
The viral hypothesis posits that a viral infection may be partly responsible for T1D. The main culprit appears to be coxsackie B—a common pathogen where, in most circumstances, the infection is asymptomatic or results in mild symptoms. (Coxsackie B, however, in rare cases, may also lead to viral meningitis, heart or brain infection, and hand, foot, and mouth disease.)
There have been no vaccines against coxsackie B, until a year ago, when the company Provention Bio started a clinical trial to test its vaccine against coxsackie infection.
This is a first-in-human study of PRV-101, and positive interim results are out. Not only was it well tolerated, but it induced high concentrations of anti-coxsackie B antibodies.
A Breakthrough T1D Story
Breakthrough T1D has been studying viral vaccines for T1D for decades, and so has the Breakthrough T1D Fund, our venture philanthropy started in 2016:
- Breakthrough T1D has been funding viruses in the development of T1D since the late 1970s and demonstrated that several common viruses known to infect humans can attack islet cells and induce symptoms resembling diabetes. But what virus? Mumps, Epstein-Barr, rubella?
- In 1994, Breakthrough T1D funded a postdoctoral fellowship for Heikki Hyöty, M.D., Ph.D., working in the lab of Michael Knip, M.D., Ph.D. The project title: “The Role of Coxsackie B and Other Enteroviruses in the Pathogenesis of Insulin-Dependent Diabetes Mellitus.” He went on to show that enteroviruses—of which coxsackie B is a member of—are the main culprit for the development of T1D. We have gone on to fund Dr. Hyöty with more than 10+ grants since, and Dr. Knip with more than 20 grants since 1997.
“One of the most critical steps was a postdoctoral grant I received from Breakthrough T1D in 1994. This grant made it possible to continue in science instead of clinical work, which I was considering at that time. I established my own research group, studying the role of virus infections in T1D, and have continued this work since then.”
– Heikki Hyöty, M.D., Ph.D.
- Hyöty and Knip co-founded Vactech in 2001, who developed PRV-01, a vaccine candidate targeting coxsackie B virus, and licensed it to Provention Bio in 2017.
- In 2017, Provention Bio* got an investment from the Breakthrough T1D T1D Fund, to get their coxsackie B vaccine into clinical trials, the start of which happened in December 2020.
Next Steps
This was only the interim results; the final results will be revealed next year. But, if they are the same as the interim results, continued development of the vaccine and its use to reduce the burden of T1D will be under way.
This vaccine is the result of decades’ long support from Breakthrough T1D and is part of the many approaches Breakthrough T1D is taking to create a world with T1D. Will you join us?
*Provention also has teplizumab, the first drug to delay the onset of T1D for nearly 3 years, under review by the FDA. Breakthrough T1D had a hand in the development of teplizumab from almost the beginning. We gave a Career Development Award to Kevan Herold, M.D., who had just started his faculty-level career at The University of Chicago, in 1988-1990. He showed, in an early animal study, that he could prevent autoimmune diabetes with an anti-CD3 antibody (which, later, became a humanized version, teplizumab). He has gone on to receive more than 15 grants from Breakthrough T1D, and was the lead on the clinical trial that demonstrated that it could delay the onset of T1D for nearly three years.
Citation: Honkimaa A, Kimura B, Sioofy-Khojine AB, Lin J, Laiho J, Oikarinen S, Hyöty H. Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells. Microorganisms. 2020 Nov 15; 8 (11): 1790. doi: 10.3390/microorganisms8111790.
On July 2, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter to Provention Bio for the use of teplizumab to delay clinical type 1 diabetes (T1D) in at-risk individuals, meaning teplizumab has not been approved for use in delaying clinical T1D in at-risk individuals at this time.
I know. It’s disappointing. But it was expected, as Provention Bio has reported that FDA raised questions about the comparability between the commercial product and the drug used in the clinical trial. Importantly, per Provention Bio’s press release, the Complete Response Letter “did not cite any clinical deficiencies related to the efficacy and safety data packages submitted.”
There is a great unmet need for disease modifying therapy for T1D; it is one of the few autoimmune diseases that still does not have a disease-modifying therapy approved.
Recently published data in the at-risk setting showed teplizumab has been able to delay the clinical diagnosis of T1D for three years in participants with a high risk of developing the disease. This was the first ever study in humans to show a delay in clinical T1D in at-risk individuals.
An Advisory Committee recommended that the Food and Drug Administration (FDA) approve teplizumab on May 27, 2021, based on data of clinical safety and efficacy, as well as unmet need in T1D. The FDA has designated teplizumab as a breakthrough therapy, indicating its potential to address a significant unmet clinical need.
It is unfortunate that the FDA has not approved teplizumab at this time. However, Breakthrough T1D is thankful for the FDA’s consideration and review of this drug and looks forward to Provention Bio addressing the issues outlined in the Complete Response Letter and working with the FDA to bring this therapy to market safely.
Breakthrough T1D’s Role
As part of our mission to accelerate life-changing breakthroughs, Breakthrough T1D played a key role in funding early-stage research, facilitating regulatory pathways, and advancing commercial development of teplizumab.
- Breakthrough T1D was one of the first to support preclinical and early clinical trials to see if the drug worked for people with type 1 diabetes.
- Breakthrough T1D gave a Career Development Award to Kevan Herold, M.D., who had just started his faculty-level career at The University of Chicago, in 1988-1990. He showed, in an early animal study, that he could prevent autoimmune diabetes with an anti-CD3 antibody (which, later, became a humanized version, teplizumab).
- Breakthrough T1D funded clinical trials in recent-onset disease, which were published in 2002, 2005, and 2013, and a phase III trial run by MacroGenics, who received a Breakthrough T1D Industry Discovery and Development Program grant from 2006-2011.
- In 2012-2019, Breakthrough T1D funded, with the National Institutes of Health (NIH), the Immune Tolerance Network—an international clinical research consortium—which did a clinical trial of teplizumab and identified who is likely to respond to the drug. We also funded, with the NIH (using funds from the Special Diabetes Program) and the American Diabetes Association, TrialNet—the largest clinical network for T1D—who ran the clinical trial in at-risk individuals, led by Dr. Kevan Herold.
- Herold currently receives Breakthrough T1D funding to investigate the mechanisms through which teplizumab delays T1D development.
- In 2017, the Breakthrough T1D T1D Fund invested in Provention Bio to facilitate the acquisition and clinical development of T1D relevant assets. The T1D Fund no longer has any financial interest in the company.
Teplizumab is the first disease-modifying therapy for T1D to be reviewed by the FDA, but it is one of many such potential therapies Breakthrough T1D is seeking to advance through its research, investment, and regulatory leadership.
Breakthrough T1D and IBM Research are collaborating to develop and apply world-class computing power to analyze years of global type 1 diabetes (T1D) data and identify factors leading to the onset of type 1 diabetes in children, and a breakthrough publication is just out. Published in Diabetes Care, it is the first major clinical paper from this collaboration on identifying people at high risk for the disease.
The Type 1 Data Intelligence (T1DI) Study—the largest one of its kind for predictors of childhood T1D, created by IBM Research—combined the data from 5 studies in 4 countries. The datasets included measurements of autoantibodies—markers that are specific to T1D.
By analyzing the data, IBM Research found that the number of autoantibodies present in blood—the earliest time point in autoimmunity development—can reliably predict risk of T1D onset in young children for periods up to 10 to 15 years into the future.
For children with multiple autoantibodies, the risk of developing T1D is very high, about 90% over a 15-year period. Also, the younger the age at which children develop multiple autoantibodies, the greater the risk, peaking between 2-4 years of age.
Breakthrough T1D-IBM Research has also shed new light on risk of T1D in single autoantibody-positive children. Their 15-year risk of T1D onset is markedly lower, just 30%, especially for children with only a single autoantibody and those remaining single after that.
Children who remain positive for only a single autoantibody, as well as having a low-risk genotype for T1D, have a substantially lower risk: Just about 12% overall, or about one third lower than those with high-risk genotypes.
Helping Identify At-Risk Children
These results not only pave the way for better understanding of risk factors for T1D, but may also help to develop guidelines for routine screening, monitoring, and management of at-risk children.
As well, T1D onset and initial diagnosis is often associated with life-threatening complications of diabetic ketoacidosis (DKA), increasing the importance of early detection. This is particularly valuable since research has shown reduced DKA rates in study participants who were routinely tested for development of autoantibodies and followed.
Our findings should also help inform screening programs—like the Breakthrough T1D initiative, T1Detect—to identify high-risk individuals early as potential candidates for clinical trials, such as in the TrialNet consortium. This could benefit not only the children who participate, but also the entire T1D research community.
Two of the participating centers in the T1DI collaboration are in the United States: DAISY at the University of Colorado, Denver, and DEW-IT at the Pacific Northwest Research Institute in Seattle. The other three centers are in Europe: DiPiS, in Sweden at the Department of Clinical Sciences Malmö at Lund University CRC, and Skåne University Hospital in Malmö. The DIPP study was conducted at multiple locations in Finland: the Institute of Biomedicine and Centre for Population Health Research at the University of Turku, Department of Pediatrics at Turku University Hospital in Turku, University of Oulu and Oulu University Hospital, Department of Pediatrics, PEDEGO Research Unit, in Oulu; and in Germany, the BABYDIAB and BABYDIET studies were conducted at Helmholtz Zentrum München in Munich.
Image credit: Artwork created by 16-year-old Sophia V. who has been living with T1D since she was five years old. See more of her work on artbymophree.com and follow her @artbymophree.
T1D doesn’t discriminate. It affects people of all races, ethnicities, ages, and socioeconomic backgrounds.
While some people are fortunate enough to be able to identify symptoms early, others learn of a T1D diagnosis during dangerously high or low blood sugars that result in hospitalization or even diabetic ketoacidosis (DKA).
In others still, T1D can be misdiagnosed as type 2 diabetes (T2D) because of implicit bias.
The risks of an emergency or incorrect diagnosis are amplified for members of underserved populations. These individuals often experience significant differences in health outcomes, due to gaps in access to adequate health care and therapies.
For instance, compared to their white peers, Black youth are more likely to experience DKA at the time of T1D diagnosis, which can contribute to a higher risk of long-term complications. According to the Centers for Disease Control’s latest report about the prevalence of diabetes in the United States, among youth under the age of 20, the rate of newly-diagnosed T1D is increasing most sharply in Hispanic and Black populations.
Learn more about T1D and health equity.
T1Detect
T1Detect, Breakthrough T1D’s screening education and awareness program, helps people in the U.S.—even those who do not have a family connection to T1D—get the information they need to determine whether they or a loved one are at risk for T1D.
T1Detect helps families understand the importance of screening, how to get screened, and what to do after they receive their results.
Knowing your T1D autoantibody status is an important first step towards determining your risk of T1D. If you don’t know your T1D autoantibody status, visit our screening education resource to learn about your options.
Learn more about type 1 diabetes screening.
When it comes to understanding your risk, knowledge is power.
Screening: A Crucial Element of Cures Research
Screening education and awareness through T1Detect is not only about preventing DKA. Screening will also accelerate the identification of people at risk of developing T1D, the development of therapies that can slow down the progression of T1D and, one day, cure T1D.
Learn more about the important role screening plays in achieving a world without T1D.
The U.S. Food and Drug Administration (FDA)’s regulatory review is now under way for teplizumab to delay clinical type 1 diabetes (T1D). Today, an FDA Advisory Committee weighed the evidence, and the vote was positive: The advisory committee recommended that the FDA approve teplizumab for at-risk individuals, with 10 members voting yes and 7 members voting no. (At-risk means that they exhibited abnormal glucose levels and at least 2 T1D-related autoantibodies, but who have not been diagnosed with the disease.)
The advisory committee heard from Aaron Kowalski, Ph.D., CEO of Breakthrough T1D, who stressed the unmet need for disease-modifying therapies—which can slow, halt, or reverse the course of the disease—for T1D. Breakthrough T1D also submitted a letter to the committee in advance of the meeting.
“A delay in onset of clinical type 1 diabetes will have long-term benefits for blood-sugar control, and the reduction in acute and long-term complications would have a tremendous impact on the daily lives of people with type 1 diabetes, their families, and our overall health system,” said Dr. Kowalski. “Beyond the important and significant clinical benefits, any person with type 1 diabetes and their family can convey the profoundly positive impact a delay in onset would have on their daily lives, and how they feel, function, and survive. It would free them from the constant burden and stress of glucose monitoring and insulin administration. It would free them from the worry and fear of short- and long-term complications while giving them the opportunity to learn more about disease management. And it would allow them to live life like those of us without type 1 diabetes are able to do. That is clinically meaningful.”
If determined by FDA to be safe and effective, teplizumab can aid in addressing the stark unmet need for disease-modifying therapies and provide people at-risk for type 1 diabetes and their families at least two more years without the burden and complications this disease brings. Disease-modifying therapies put us on the critical pathway to preventing and ultimately curing T1D.
Breakthrough T1D thanks the committee for their thorough and considerate review of the evidence and future impact of teplizumab. If approved, teplizumab will be the first disease-modifying drug for individuals at-risk for developing T1D. The target action date by the FDA is July 2, 2021, however the sponsor, Provention Bio, has stated it will likely be delayed.
Breakthrough T1D had a hand in the development of teplizumab from nearly the beginning:
- Breakthrough T1D was one of the first to support preclinical and early clinical trials to see if teplizumab worked for people with T1D.
- We gave a Career Development Award to Kevan Herold, M.D., who had just started his faculty-level career at The University of Chicago, in 1988-1990. He showed, in an early animal study, that he could prevent autoimmune diabetes with an anti-CD3 antibody (which, later, became a humanized version, teplizumab). He has gone on to receive more than 15 grants from Breakthrough T1D, and was the lead on the clinical trial that demonstrated that teplizumab could delay the onset of clinical T1D for nearly three years in people almost certain to develop the disease. This was the first ever study in humans to show a delay in the onset of T1D.
- We funded clinical trials in recent-onset disease, which were published in 2002, 2005, and 2013, and a phase III trial run by MacroGenics, who received a Breakthrough T1D Industry Discovery and Development Program grant from 2006-2011.
- In 2012-2019, we funded, with the National Institutes of Health (NIH), the Immune Tolerance Network—an international clinical research consortium—which did a clinical trial of teplizumab and identified who is likely to respond to the drug. We also funded, with the NIH (using funds from the Special Diabetes Program) and the American Diabetes Association, TrialNet—the largest clinical network for T1D—who ran the clinical trial in at-risk individuals, led by Dr. Kevan Herold.
- In 2017, the Breakthrough T1D T1D Fund invested in Provention Bio to facilitate the acquisition and clinical development of T1D relevant assets. The T1D Fund no longer has a financial interest in the company.
If successful, and the FDA review results in approval, we will be moving ever closer to a world without this disease.
Breakthrough T1D is honored to celebrate National DNA Day, to commemorate the day in 1953 when the structure of DNA was published. We have learned a great deal about type 1 diabetes (T1D) DNA in the 65 years since that publication. We know that genes can influence someone getting T1D. And we know what genes are responsible. A major component is the group of human leukocyte antigen (HLA) genes. HLA genes account for more than half of the genetic risk of developing T1D. Other responsible genes include the genes for insulin, and CTLA-4, which has a regulatory role in the immune response. There are still other genes that play a minor part.
HLA genes have an enormously crucial role in the immune system. They encode molecules that allow the immune cells to decide if a cell is good (i.e., self cells) or bad (non-self cells, like viruses, bacteria, or tumor cells). Unfortunately, inheriting certain versions of the HLA genes increases the probability that immune cells will attack the body’s healthy cells. When this happens, an autoimmune disorder will develop. HLA genes are associated with a number of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, celiac disease, and T1D.
For T1D, HLA variants can increase the risk or offer protection. Let’s take the HLA gene called HLA-DQ. In T1D, HLA-DQ6 is protective. But HLA-DQ8 puts one at risk. About 50 to 60 percent of people with T1D have the HLA-DQ8 variant. The dichotomy of risk between the two variants highlights the importance of the immune system within T1D development.
A Blood Pressure Drug for T1D?
It’s one thing to understand genes, but quite another to develop a treatment that will either enhance or limit the genes’ behavior, hopefully making a difference in the lives of people with T1D. That’s what Breakthrough T1D researcher Aaron Michels, M.D., from the University of Colorado, is trying to do.
HLA-DQ8 is an attractive treatment target, and Dr. Michels hypothesized that blocking the HLA-DQ8 would represent a novel pathway for treating T1D. He discovered that methyldopa—a therapy that has been used for 50 years to treat high blood pressure—could have a role in impeding HLA-DQ8 and subsequent immune destruction of beta cells.
In the clinical trial, Dr. Michels recruited people who had newly onset T1D and were HLA-DQ8-positive and gave them methyldopa for six weeks. The results were exciting (although there were only 20 people to weigh in!). Methyldopa caused a reduction in immune cell responses toward insulin, suggesting that it may limit beta cell destruction and preserve function.
Breakthrough T1D not only funded the clinical trial, but also funded the investigations by Dr. Michels that uncovered the role that methyldopa might have in delaying the onset of T1D.
In 2017, Dr. Michels and Peter Gottlieb, M.D., started ImmunoMolecular (IM) Therapeutics, and, in 2019, the Breakthrough T1D T1D Fund—BreakthroughT1D’s innovative venture philanthropy fund—made a catalytic investment in IM Therapeutics, to bring the company to clinical trials of IMT-002, which is based on methyldopa.
To read more about Dr. Michels’s research, go to the Breakthrough T1D blog here.
