As the leading global type 1 diabetes (T1D) research and advocacy organization, Breakthrough T1D helps make everyday life with the condition better while driving toward cures. We won’t stop until the condition is a thing of the past.

That means powering research to cure, prevent, and better treat T1D and its complications and ensuring that the entire T1D community has access to the tools they need to thrive.

Explore our research.

Breakthroughs past, present, and future

For more than 50 years, Breakthrough T1D has played a pivotal role in nearly every major T1D breakthrough—from how HbA1c came to be more than 40 years ago to recent advancements like advanced T1D management devices, such as artificial pancreas (AP)/automated insulin delivery (AID) systems. Our work has also ensured that people have access to these advances.

Let’s have a look at some of the biggest breakthroughs we’ve advanced that are improving lives right now and those that promise to improve lives in the future.

The first disease-modifying therapy for T1D

In 2022, the FDA approved Tzield™ (teplizumab-mzwv) for use in delaying the onset of clinical T1D. This was the first disease-modifying therapy (DMT) for T1D to be approved. These are treatments that can slow, halt, or reverse the course of a condition. It took decades of Breakthrough T1D research for Tzield to reach approval.

Beginning with basic research by Kevan Herold, M.D., in the 1980s to preclinical and early clinical trials to a strategic investment from the T1D Fund: A Breakthrough T1D Venture that brought Provention Bio—the company that launched Tzield—into T1D for the first time, in 2017.

“The story with the clinical use of teplizumab began with a Breakthrough T1D grant to support a trial in patients with new-onset type 1 diabetes more than two decades ago. The success of this initial study planted a seed that led to further studies and support from the NIH.”

Kevan Herold, M.D.
Yale School of Medicine

But there’s a personal story, too.

Andy Drechsler and his wife Moira are the parents of four children; three of them have T1D. They have been involved with Breakthrough T1D since their son was diagnosed at the age of 22 months in 2005.

Andy’s professional life intersected with his personal life when he helped start Provention Bio in 2017.

“Everyone living with T1D provides us with great inspiration. We also appreciate the parents and caregivers of T1Ds. We are so happy to see the improvements in pumps and CGMs for those living with T1D. We are also thrilled to see therapies to delay the onset. Ultimately, we are confident that therapies will allow many to live without T1D someday.”

Andy Drechsler
Board of Directors President
Breakthrough T1D New Jersey Metro and Rockland County Chapter

We are moving ever closer to a world without this disease. Tzield is one gigantic step along the way, and others are right behind it. Read about the other disease-modifying therapies in our pipeline to learn about the drugs that could become the “next Tzield.”

T1D management devices—decades in the making

For 20+ years, Breakthrough T1D spearheaded efforts to develop artificial pancreas (AP) systems—also called automated insulin delivery (AID) systems. We would go on to fund more than 150 grants, including 50+ clinical trials, funded by us and backed by our Artificial Pancreas Consortium, to make the artificial pancreas system a reality.

Thanks to Breakthrough T1D research and advocacy efforts, approximately 15 FDA-approved T1D management devices are on the market today—more than half of them AP systems and the remainder, advanced CGMs and insulin pumps.

Read about the different AID systems that the U.S. Food and Druge Administration has approved in recent years.

“Witnessing the progression of T1D breakthroughs over the years has been nothing short of remarkable. When I first started insulin injections, it was a cumbersome routine, requiring multiple injections a day. Today, thanks to advancements in insulin pump technology, managing T1D has become more streamlined and efficient, improving my quality of life.” 

Princess Padmaja Kumari Parmar
Breakthrough T1D Global Ambassador

Early detection empowers families, helps advance research

T1D develops in stages over time. Early detection identifies people who have early-stage T1D, but no symptoms, by a simple blood test. It looks for markers in their blood called autoantibodies. These autoantibodies signal that the body’s immune system is attacking the insulin-producing cells in the pancreas.

Autoantibodies also have value in identifying individuals who would later develop T1D, providing a new staging for presymptomatic T1D. The presence of two or more means that your lifetime risk of getting T1D is nearly 100 percent.

Early detection gives families time to plan and prepare before the onset of the condition, prevents life-threatening complications and hospitalization at the onset of symptoms. Critically, it also identifies at-risk people who can take advantage of preventive therapies—including disease-modifying therapies such as Tzield—or participate in clinical trials for T1D therapies being developed.

NFL Super Bowl Champion Orlando Brown, Jr., knows all too well how dramatically T1D can impact families, as his late father and his younger brother were both diagnosed with T1D.

In his role as Breakthrough T1D ambassador, the Cincinnati Bengals offensive tackle strives to educate people about T1D and the importance of T1D early detection and research. He also uses his platform to advocate for insulin affordability and policies like the Special Diabetes Program (SDP). Last summer, he was one of 10 Celebrity Role Models at Breakthrough T1D Children’s Congress.

Learn about our program, Breakthrough T1D Early Detection.

“The sudden loss of my father to diabetic ketoacidosis and my younger brother’s type 1 diabetes diagnosis at just 11 years old brought us face-to-face with uncertainty and the stigmas surrounding this condition. However, as we learned about diabetes devices and treatments to help manage the disease, we discovered a renewed sense of peace and hope. With more research, we believe we can ultimately end this disease. Knowledge is power and I’m sharing my family’s story to educate and inspire others who are living with type 1 diabetes.” 

Orlando Brown, Jr.
NFL Super Bowl Champion
Breakthrough T1D Ambassador

Breakthrough in progress: stem cell-derived replacement therapies

Cell therapies replace beta cells in the bodies of people with T1D so that they can again produce their own insulin​.

Biotech powerhouse Vertex Pharmaceuticals is making major headway in its goal of developing stem cell-derived replacement therapies for T1D. This work being advanced by Vertex has been supported by Breakthrough T1D for decades.

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. Several people who have received VX-880 have been able to stop taking insulin.

This work was pioneered by Doug Melton, Ph.D., whose years of Breakthrough T1D-funded research led to successfully transforming stem cells into beta cells in 2014. A catalytic investment from the T1D Fund in Semma Therapeutics—the biotech company Melton founded to develop a stem cell-derived islet therapy for T1D—was followed years later by Vertex acquiring Semma. Vertex also acquired ViaCyte, which like Semma, had received support from Breakthrough T1D and the T1D Fund for its cell therapies research.

See the timeline of Breakthrough T1D’s support of stem cell-derived islet replacement therapies.

Douglas Melton Beta Cells

“My lab research has been for more than a decade or two, trying to cure type 1 diabetes. That might sound like an overly ambitious project, but I believe it’s a solvable problem. Our lab worked for years to figure out how to turn stem cells into functional beta cells. We can now make billions of functional beta cells.”

Doug Melton, Ph.D.
Vertex Pharmaceuticals Research Scholar

We are Breakthrough T1D

Breakthrough T1D is knocking on the door of something big. Giant leaps are happening nearly every day. You have gotten us to where we are today—and you can help us get to the finish line faster. So that you, your loved ones, and people everywhere can enjoy a world free from the burden of T1D. A world where people don’t have to manage their diabetes—don’t take insulin, don’t have blood sugar highs and lows, and don’t develop complications. With your ongoing support, we won’t stop until this condition is a thing of the past.  

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Last year, Tzield became the first disease-modifying therapy (DMT) approved for type 1 diabetes (T1D). Breakthrough T1D’s disease-modifying therapy pipeline is stocked with other therapies that have the potential to join it as an approved therapy in the US and worldwide.

Disease-modifying therapies are one of, if not the, top success stories of T1D research in 2023. From CLVer to BANDIT to PROTECT, there have been multiple updates on various therapies that can help people with T1D and those at risk for developing it.

This blog highlights eight disease-modifying therapies, including one that is FDA-approved for those at risk for developing type 1 diabetes, their effect in T1D, current research, and more.

Let’s dive in!

What Are Disease-Modifying Therapies?

Disease-modifying therapies are one of the pillars of Breakthrough T1D’s strategy to accelerate the development of cures for T1D.

A disease-modifying therapy is exactly what it sounds like—a therapy that alters the course of a disease. A DMT for T1D is any therapy that slows down the progression of T1D, halts its progression, or reverses it entirely.

Breakthrough T1D is focused on two main tactics to develop DMTs for T1D:

  1. Stop the immune system from attacking healthy beta cells, preventing T1D from ever occurring.
  2. Spur beta cell growth safely and protect beta cells, so people with T1D can live without life-long external insulin.

If we can discover a therapy, or combination of therapies that prevent T1D onset and, eventually, reverse it altogether, we will have discovered cures for T1D.

“Type 1 diabetes does not happen all at once—it’s a progression,” said Esther Latres, Ph.D., Breakthrough T1D vice president of research. “For some, the autoimmune process has begun but they are asymptomatic. Others have had T1D for decades and make virtually no insulin. Breakthrough T1D is focused on DMTs that can help everyone with T1D, no matter where they are on the disease continuum.”

The Path Toward Disease-Modifying Therapies

Thanks to decades of Breakthrough T1D-funded work, multiple potential disease-modifying therapies have shown efficacy in altering the course of T1D in people—not just in mice. One of them, Tzield, received FDA approval and is being used in individuals at risk for developing T1D.

There’s also, thanks to Breakthrough T1D and our collaborators, a regulatory pathway for DMTs to receive FDA approval.

Right now, there are multiple disease-modifying therapies approved for other diseases that have shown they can protect and preserve beta cell health in people with T1D.

People who receive these therapies after diagnosis continue to make more of their own insulin, measured by the amount of C-peptide in their blood, than those on placebo. This is a significant finding pointing to the potential application of these therapies to T1D.

According to a new publication made possible by Breakthrough T1D support, “modest concentrations of C-peptide in type 1 diabetes are associated with better clinical outcomes including reductions in hypoglycemia, neuropathy, and retinopathy.” More C-peptide, better outcomes.

Here’s a rundown of several DMTs that, through Breakthrough T1D-funded studies, have the potential to join Tzield as an approved DMT for T1D.

Abatacept

Abatacept

What It Is: Abatacept is a drug that reduces inflammation by inhibiting the activity of the T cells. It is currently approved for use in autoimmune disorders, like rheumatoid arthritis.

Effect in T1D: In 2011, a Breakthrough T1D-funded study showed that individuals receiving abatacept had higher levels of C-peptide compared to placebo.

Current Research: Breakthrough T1D is funding a follow-up study in Australia that uses a nasal insulin as a tolerizing agent to see if using tolerizing agents and immunotherapies at the same time can lead to longer-lasting results.

Breakthrough T1D Role: Breakthrough T1D has supported the development of abatacept for over 15 years and is currently funding a follow-up study.

ATG

ATG

What It Is: Anti-thymocyte globulin (ATG) is an FDA-approved drug used to increase white blood cell counts in individuals receiving chemotherapy or transplantation.

Effect in T1D: The Diabetes TrialNet ATG-GCSF New Onset Study found that, after two years, low-dose ATG preserved beta cell function and improved insulin production in individuals newly diagnosed with T1D. People on ATG-alone also had lower A1c levels.

Current Research: There are several Breakthrough T1D-supported studies continuing this research. This includes:

Breakthrough T1D Role: Breakthrough T1D has supported the development of ATG for over 10 years and is currently funding follow-up studies.

Baricitinib

Baricitinib

What It Is: Baricitinib is a JAK inhibitor currently approved for use in autoimmune disease, including rheumatoid arthritis and alopecia.

Effect in T1D: In a Breakthrough T1D-funded clinical trial published in the renowned New England Journal of Medicine, investigators demonstrated that baricitinib—a JAK inhibitor, which is critical to signaling pathways within both immune cells and beta cells in T1D—preserved beta cell function in the disease.

Current Research: There are several clinical trials to see if JAK inhibitors, like baricitinib, can be effective if used in conjunction with other therapies, such as Tzield or verapamil, in presymptomatic disease, or in longer duration.

Breakthrough T1D Role: Breakthrough T1D, along with Breakthrough T1D Australia, funded the seminal BANDIT study which showed that baricitinib can preserve insulin production in adolescents and teens recently diagnosed with T1D.

Diamyd

Diamyd

What It Is: Diamyd is an antigen-specific immunotherapy, directed toward the autoantigen GAD, to stop the autoimmune destruction of insulin-producing cells. Based upon strong clinical evidence, this therapy is the first to be targeted to a specific T1D sub-population: individuals with the HLA DR3-DQ2 gene, a genetic risk factor for T1D, and presence of antibodies to the GAD antigen. Collectively, this accounts for almost 40% of people with newly diagnosed T1D.

Effect in T1D: In a Phase I/II study, Diamyd demonstrated statistically significant and clinically meaningful beneficial effects on preservation of insulin production and blood glucose control.

Current Research: Diamyd is conducting the DIAGNODE-3 Diabetes Study which will test the safety and efficacy of the therapy in approximately 330 adolescents and young adults aged 12-29 recently diagnosed with T1D.

Breakthrough T1D Role: Breakthrough T1D is funding the DIAGNODE-3 Diabetes study.

Golimumab

Golimumab

What It Is: A monoclonal antibody that inhibits TNF alpha, a chemical messenger that leads to inflammation and increases the immune response to beta cells.

Effect in T1D: Results published in the New England Journal of Medicine in 2020 demonstrated children and adolescents newly diagnosed with T1D who received golimumab produced more insulin compared to placebo.

Current Research: Breakthrough T1D is pursuing this class of drugs to see potential future uses in DMT.

Breakthrough T1D Role: Breakthrough T1D has partnered with other funders to validate the results of this study in combination with another therapy that also preserves C-peptide.

Rituximab

Rituximab

What It Is: Rituximab is a monoclonal antibody medication used to treat certain autoimmune diseases, like rheumatoid arthritis, and types of cancers. It is the only one of the DMTs discussed in this piece that target B cells, the cells that activate the cells that destroy the beta cells.

Effect in T1D: A study by TrialNet showed that rituximab preserved beta cell health in individuals recently diagnosed with T1D.

Current Research: TrialNet is conducting the T1D RELAY study to see if two immune therapies that have shown benefit in T1D—rituximab-pvvr, followed by abatacept—can together preserve insulin production in people recently diagnosed with T1D.

Breakthrough T1D Role: Breakthrough T1D’s work is closely aligned with TrialNet in efforts to develop DMTs for T1D. Breakthrough T1D is currently supporting research into B cells, which is what rituximab targets.

Tzield

Tzield

What It Is: Tzield (teplizumab-mzwv) is an anti-CD3 monoclonal antibody, FDA approved to delay onset of T1D in at-risk (stage 2) individuals.

Effect in T1D: Tzield delays the progression of T1D by a median of 2.7 years in individuals with multiple autoantibodies and abnormal blood sugar levels. Tzield is the first FDA-approved DMT for T1D.

The results of the PROTECT study, which were recently published in the New England Journal of Medicine, showed that newly-diagnosed individuals can also benefit from this therapy.

Current Research: There are multiple studies, including the Ver-a-T1D trial, to see if Tzield can be used in combination with other therapies to delay T1D progression.

Breakthrough T1D Role: Breakthrough T1D has supported the development of teplizumab for more than 30 years.

Verapamil

Verapamil

What It Is: Verapamil is a generic calcium channel blocker used primarily to treat high blood pressure.

Effect in T1D: Multiple Breakthrough T1D-funded studies, including the CLVer study, have shown that verapamil can preserve beta cells in newly diagnosed individuals.

Current Research: Breakthrough T1D is currently funding a follow-up study for three years to see if C-peptide benefits persist. Additionally, Breakthrough T1D is funding several clinical trials to validate the results of this study and see if verapamil is effective when used in conjunction with other disease-modifying therapies, such as Tzield.

Breakthrough T1D Role: Breakthrough T1D has supported research into verapamil for more than 20 years.

What Comes Next for Disease-Modifying Therapies?

The journey from discovery research to regulatory approval and global access to a drug is long and expensive. Very few therapies make it all the way through because of the vast evidence and resources required.

“Breakthrough T1D wants new therapies to prove safe and effective and get through the regulatory process as efficiently as possible,” said Campbell Hutton, Breakthrough T1D vice president, regulatory and health policy. “We have a team at Breakthrough T1D that works with regulators and industry to ensure this happens. We help establish regulatory pathways, update regulators on the state of T1D science so they are ready to review these new therapies, make sure there is a common understanding of the risks and benefits of new therapies, and more.”

The clinical data reviewed above is critically important for future regulatory approvals. Thanks to dedicated researchers and the contributions of the Breakthrough T1D community, we have significant amounts of data that show the promise of these therapies for people with T1D or at-risk for developing it. However, to achieve regulatory approval, the data, in some cases, will need to be replicated with more people for a longer time.

Even after having the clinical trial data needed, a sponsor, or the company who makes the drug, needs to submit the data and other information, like on the manufacturing of the drug, to FDA (the regulatory agency in the U.S.) for it to be reviewed. If a drug is owned by a single pharmaceutical company, they are responsible for submitting the application as the sponsor. If a drug’s patent has expired and is made by multiple companies, it can be challenging to find a company willing to engage in the long and expensive regulatory process.

Breakthrough T1D plays a key role here, encouraging industry to support clinical research and take the necessary steps to get these therapies to market.

As you can see, this is a complicated process, which is why Breakthrough T1D has filled the pipeline with therapies that all have a decent shot of making it to market.

Breakthrough T1D Enabling Progress in Disease-Modifying Therapies

Breakthrough T1D is the only organization that supports therapy development at every stage—from discovery research all the way through to people with diabetes receiving these therapies—with healthcare coverage paying for them. This is a lengthy and expensive process; success requires many stakeholders to come together toward a common goal. Breakthrough T1D plays a crucial role here to ensure this collaboration happens and everyone, from researchers to regulators to payers—are all pulling in the same direction.

Breakthrough T1D is committed to having multiple shots on goal to cure T1D. The DMT pipeline, as evidenced by the eight DMT candidates above, is proof of that commitment.

Hopefully in the future one of these, or other therapies, will join Tzield and give the T1D community another option for delaying, halting progression, or eventually reversing this disease.

Key Terms to Know

We know type 1 diabetes research has its own language. Here’s a quick refresher on frequently-used terms.

Antibody – blood protein created in response to an antigen

Antigen – something that causes an immune response

Beta cells – cells in the pancreas that produce insulin. These are the cells destroyed by the immune system in people with T1D.

C-peptide – a biomarker that indicates the presence of insulin production. When the body produces insulin, it also creates C-peptide.

HbA1c – a blood test used to measure average blood glucose levels over the past three months.

Immunotherapy – drug aimed at altering the body’s immune system. Specifically, immunotherapies for T1D are intended to disrupt the autoimmune attack behind T1D. Also called “immune therapies.”

Placebo – A treatment, such as a dummy pill, that does not contain any of the drug being tested.

In a Breakthrough T1D-funded clinical trial, published in the renowned New England Journal of Medicine, Thomas Kay, M.B.B.S., Helen Thomas, Ph.D., and others demonstrated that baricitinib—a JAK inhibitor, which is critical to signaling pathways within both immune cells and beta cells in type 1 diabetes (T1D)—preserved beta cell function in the disease.

In 60 newly diagnosed children and young adults, baricitinib:

The effect of baricitinib was achieved using a single daily oral tablet, and it’s the first immunotherapy trial to suggest a benefit on CGM measures. (Verapamil, a once-a-day tablet, also preserved beta cell function, but without improvement in CGM measures or insulin requirement.)

What Comes Next?

Baricitinib is not an FDA-approved therapy for people with T1D, but Breakthrough T1D has multiple lines of inquiry to make sure that this and other disease-modifying drugs get to the hands of people with the disease. There are several clinical trials that Breakthrough T1D is exploring to see if baricitinib can be effective if used in conjunction with other therapies, such as Tzield™ (teplizumab-mzwv) or verapamil, in presymptomatic disease, or in longer duration.

But this adds to the armamentarium of potential curative therapies, and Breakthrough T1D is excited to be a part of the team that made this advance possible.

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 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 

 Newly-Approved Continuous Glucose Monitoring (CGM) Systems  

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 

Celebrating the Best of 2021 

What We Can Be Proud Of in 2020 

Top 10 T1D Breakthroughs of 2019 

There are many unique challenges that need to be addressed to cure type 1 diabetes (T1D). For example, it’s incredible that, thanks to years of Breakthrough T1D funding, stem cell-derived insulin-producing beta cells created in a lab are in human clinical trials. However, this won’t translate into a cure for everyone with T1D until those cells can thrive inside the body to fully regulate blood-glucose levels without the use of broad immunosuppression. It’s an incredibly complex engineering and immune challenge, which is why Breakthrough T1D and the National Institutes of Health (NIH) brought together the top minds in these fields to discuss new technologies, approaches, and strategies.

Over two days, from July 27-28, nearly fifty scientists from a variety of scientific disciplines, including transplant immunology and bioengineering, assessed the scientific landscape, identified knowledge gaps and barriers, and outlined a roadmap to achieving localized immune modulation and immune tolerance key to implanted beta cells thriving in the body.

“We are very excited about the potential for cutting-edge research at the intersection of immunology and bioengineering,” said Jaime Giraldo, Ph.D., Breakthrough T1D Associate Director, Research. “It’s critical that Breakthrough T1D provides the opportunity to explore unique approaches for protecting transplanted cells, allowing for the next generation of beta cell replacement therapies to benefit a broad patient population. While we remain enthusiastic about the progress made with encapsulation technologies and their potential to address the challenges we face in creating beta cell replacement therapies, we are also encouraged at the prospect of next-generation technologies that can enable cell survival and function, without the need for physical barriers to protect the cells.”

Different Approaches, Same Goal

In order to protect the beta cells put into people to cure their T1D, they must be kept safe from the immune system. This can be done through localized immune modulation and induced immune tolerance.

Localized immune modulation creates small areas in the body that are immune privileged, which means they can tolerate the introduction of antigens—the alarm sirens secreted by beta cells—without eliciting an inflammatory response. This could be accomplished by:

Inducing immune tolerance means teaching the body’s immune system to ignore and not mount an attack against certain stimuli. In T1D, people are missing immune tolerance to some of their beta cell proteins, which allows the body’s immune system to destroy their beta cells, giving them T1D.

These approaches have the potential to create an environment that allows a transplanted beta cell to flourish in an individual with T1D—safe from the autoimmune attack that created T1D in the first place.

Breakthrough T1D’s Strategy: Get the Top Minds Together

Breakthrough T1D’s approach to solving complex problems involves bringing a diverse set of experts to explore myriad solutions. This workshop featured immunologists, material scientists, biomedical engineers, and transplant specialists, among others, to brainstorm potential solutions and collaborations that have not been possible before.

“It was a great pleasure to work with Dr. Giraldo and the Breakthrough T1D team in the organization of this successful workshop that attracted an outstanding group of speakers, moderators and participants who discussed current therapeutic barriers and how to tackle them with immuno-engineering solutions enabling more effective and durable interventions in the context of cell replacement therapies for immune mediated diabetes,” said Dr. Guillermo Arreaza-Rubín, M.D. Director, Clinical Immunology and Diabetes Technology Program. “Workshops like this one allow our agencies to better coordinate and catalyze efforts to promote cutting edge and translational research in key priority areas”

This group came to the consensus that, while this technology has come a long way in recent years, there is still some work to be done before it becomes a commercially available therapy. Breakthrough T1D plans to take this information and create funding opportunities aimed at addressing fundamental gaps in knowledge needed to move forward, while continuing to push on other key approaches in cell replacement therapy such as encapsulation, oxygenation, gene modification, clinical development and others.

Not only was the workshop a productive two days of information sharing and brainstorming, but it was also a return to normalcy for Breakthrough T1D research. Interdisciplinary workshops have been key in forming the relationships and partnerships that produce solutions to complex problems which have brought T1D science to where it is today. This workshop was the first Breakthrough T1D hosted since the pandemic began in 2020.

Learn more about Breakthrough T1D’s work in cell therapies here.

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.

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.

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:

If successful, and the FDA review results in approval, we will be moving ever closer to a world without this disease.

Did you know that people with type 1 diabetes (T1D) are more likely to have a coexisting autoimmune disease? And someone with T1D is at a more than 3-fold increased risk of developing multiple sclerosis, as compared to someone who does not have type 1? And, if you have T1D and lupus, you are more likely to develop kidney complications, as opposed to people with just one disease.

That’s why Breakthrough T1D partnered with the Lupus Research Alliance and the National Multiple Sclerosis Society to advance the understanding of autoimmunity and to obtain more specific insights into commonalities and differences of immune pathways that govern these disease processes.

With the recent advances in immunology and the advent of innovative technologies, including advanced machine learning capabilities, autoimmune communities can now ask new questions or revisit old ones with new tools and for deeper, new insights.

“As far as technologies and methodologies go, we are in unprecedented times,” said Simi Ahmed, Ph.D., director of disease-modifying therapies at Breakthrough T1D and the architect behind this initiative. “The depth of information these tools can generate is remarkable and can shed light on key questions that remain unanswered for autoimmune diseases.”

“The best part is that three research organizations have joined forces to address knowledge gaps of mutual relevance for mutual benefit,” she adds. “This really is a fitting example of team science.”

The researchers will get a maximum of $450,000 for up to 2 years to generate the first tranche of results from their projects, which are outlined below.

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling, to mobility challenges, blindness, and paralysis. An estimated 1 million people live with multiple sclerosis in the United States.
Lupus (systemic lupus erythematosus) is a debilitating condition in which the immune system mistakenly attacks the tissues in the body, such as your tendons, skin, internal organs, bones, and joints. An estimate suggests 322,000 Americans have definite or probable lupus.

Researchers Funded

Amit Bar-Or, M.D., University of Pennsylvania
Linking multiple disease compartments in T1D and multiple sclerosis
Dr. Bar-Or’s study will provide immune cell profiles in three distinct sites: target organ-associated immune cells, tissue-draining lymphatic immune cells, and circulating blood—the first to be able to do so—in type 1 diabetes and multiple sclerosis, with the goals of exploring hidden immune compartments, determining blood measures that better correspond with what is happening in the tissue being injured, and targeting them therapeutically.

Chris Cotsapas, Ph.D., Yale University
Identification of pathogenic pathways through genomic engineering to identify shared genetic effects on people with T1D, SLE, and MS
Dr. Cotsapas has developed a set of diagnostic tools to compare genetic information from different diseases and identify the regions in the genome (DNA) associated with the disease risks. He will use genome engineering—a way to make changes in the DNA—to determine the effect of a specific alteration of the DNA on the function of immune cells and uncover the biological basis for risk shared across autoimmune diseases, and find specific pathways that can be targeted for drug development.

Kevan Herold, M.D., Yale University
Analysis of antigen specific T cells in response to immune therapies in MS and T1D
Dr. Herold will study the immune cells that have been activated for target-organ molecules, in type 1 diabetes and multiple sclerosis, to identify features that account for their ability to cause autoimmunity, and will use anti-CD20 antibodies—an immunotherapy that targets immune cells called B cells—to find out how they change immune cells called T cells.

Thomas Pieber, M.D., University of Graz, Austria
COMET common mechanisms in autoimmunity
Dr. Pieber will apply advanced machine-learning approaches on existing data from people with type 1 diabetes, lupus, multiple sclerosis, and rheumatoid arthritis and healthy volunteers, to identify the shared or differential characteristics of their immune cells, which could uncover important pathways to be targeted for potential therapies.

William Robinson, M.D., Ph.D., Stanford University
Dissecting the genetics and host interactions of EBV-related autoimmunity
Dr. Robinson’s study will apply next-generation technologies to determine how Epstein-Barr virus (EBV) can trigger autoimmunity in multiple sclerosis and lupus. Understanding the mechanism underlying EBV’s role in autoimmunity could lead to the development of targeted therapies for these diseases.

Ansuman Satpathy, M.D., Ph.D., Stanford University
3D and single-cell epigenome technologies for autoimmune disease
Dr. Satpathy will use the latest technology that can obtain genomic information at a single cell level to identify the molecular pathways that cause autoimmune disease—including type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis. He anticipates that these studies will provide novel insights into the shared and disease-specific mechanisms governing each disease that could lead to new therapeutic intervention.

Alexandra-Chloé Villani, Ph.D., Massachusetts General Hospital/Harvard Medical School
Single-cell genomics dissection of common immune networks driving autoimmunity
Using new state-of-the-art technologies called single-cell multi-omics, which combines the comprehensive nature of genomics with the microscopic resolution required to reveal distinct insights in the molecular make-up of every single cell comprised in tissues, Dr. Villani will compare the cell type and characteristic of each single cell from blood and tissue samples collected from healthy people and people with autoimmune diseases. Identifying the composition, state of the cells, and transcriptional programs making up the tissues and blood specimens obtained from different diseases will enable to pinpoint the biological processes and pathways shared between diseases that could be targeted for therapeutic potential.

Julie Zikherman, M.D. (with Samuel Pleasure, M.D., Ph.D., Michael Wilson, M.D., Judith Ashouri, M.D., Joseph Derisi, Ph.D., who will serve as co-investigators), University of California, San Francisco
NR4A family as markers and mediators of B cell tolerance across autoimmune diseases: From antigen discovery to treatment
Self-reactive B cells can produce autoantibodies that mistakenly tag the body’s own cells as foreign and trigger an attack by the immune system. Dr. Zikherman and co-investigators will take advantage of the unique expression of genes in the NR4A family to identify these cells, and will couple this approach with a novel high-throughput phage-display platform to identify autoantigens and autoantibodies in people with type 1 diabetes, multiple sclerosis, and lupus.

A lot of autoimmune diseases have disease-modifying therapies, which are treatments that can slow, halt, and reverse disease progression. Rheumatoid arthritis. Lupus. Multiple sclerosis.

What isn’t on the list? Type 1 diabetes (T1D). T1D remains one of the only major autoimmune diseases that does not have a licensed disease-modifying therapy.

A Breakthrough T1D-funded clinical trial is aiming to change that.

Clinical Trial Overview

The investigators will test the hypothesis that simultaneous inhibition of two immune cell pathways—interleukin-17 and interferon-gamma, which are thought to drive T1D—will halt the progression of, or reverse, disease in participants with recent-onset T1D.

The hope is that, if the drug can block immune cells soon after the development of diabetes, any remaining insulin-producing cells may be protected and regenerate, producing more insulin so that people with T1D may be insulin free or require less insulin for a longer period of time.

How will they do that?

With a drug called ustekinumab (oos·teh·KIN·yoo·mab). Ustekinumab—made by Janssen and sold under the name Stelara® for the treatment of psoriasis (which affects the skin), Crohn’s disease (an inflammatory bowel disease), and other autoimmune conditions—is a monoclonal antibody that inhibits two molecules that regulate the immune system.

It’s already approved, meaning that, if the clinical trial results are positive, translation to clinical use would not only be feasible, but rapid.

Where will it take place and how many will be recruited?

The phase II/III trial is taking place at BCDiabetes in Vancouver, under the leadership of Tom Elliott, MBBS, and the University of Toronto, under Bruce Perkins, M.D., MPH, both in Canada. There will be a total of 60 participants, ages 18-25, enrolled.

There is also a trial testing ustekinumab in teens, aged 12-18, within 100 days of diagnosis, in various locations of the United Kingdom, and a Breakthrough T1D grant to Megan Levings, Ph.D., at the BC Children’s Hospital Research Institute, will harmonize the biomarkers of response in both of the clinical trials, thereby increasing the sample size and more rapidly identifying whether or not this is an effective therapy for T1D.

What were the results of other clinical trials of ustekinumab in T1D?

The pilot study by Jan Dutz, M.D.—who is also the lead on the phase II/III study—showed that ustekinumab is safe in the treatment of participants with recent-onset T1D.

How will I learn more?

You can contact Marla Inducil, B.Sc. Pharm, M.D., CCRP, at 604-628-7253 ext. 7011 or [email protected]. She is responsible for managing and executing all clinical trials at BCDiabetes located in Vancouver.