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 minducil@bcdiabetes.ca. She is responsible for managing and executing all clinical trials at BCDiabetes located in Vancouver.

The U.S. Food and Drug Administration (FDA) regulatory review is now under way for teplizumab—a therapy that blocks the blood marker CD3, which activates immune cells—to prevent or delay type 1 diabetes (T1D) in at-risk individuals. The target action date is July 2, 2021.

Teplizumab could become the first disease-modifying therapy approved for T1D.

Breakthrough T1D had a hand in the development of teplizumab from nearly the beginning:

Teplizumab, now called PRV-031, is also being tested in a phase III clinical trial in people who have been recently diagnosed, headed by Provention Bio, a company with an investment from the Breakthrough T1D T1D Fund.

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

Many scientists enter their fields hoping that their work will directly impact people’s lives. That is exactly what Thomas Kay, M.B.B.S., and Helen Thomas, Ph.D., at the St. Vincent’s Institute of Medical Research (SVI), in Australia, wanted to do for type 1 diabetes (T1D).

Through their research, they discovered that inhibition of a protein, called JAK, may work in slowing down or preventing beta cell loss.

JAK—otherwise known as Janus kinase—is critical to signaling pathways within both immune cells and beta cells in T1D. It is therefore a very attractive target for the correction of both immune and beta cell defects in T1D.

Kay and Thomas now have a clinical trial, funded by Breakthrough T1D, to find out if a JAK inhibitor, called baricitinib, will preserve beta cell function in children and young adults with recently diagnosed T1D. (It’s called BANDIT, which stands for BAricitinib in New-onset type 1 DIabeTes.)

“It is tremendously exciting for us to be the first group anywhere in the world to test the efficacy of baricitinib as a potential type 1 diabetes treatment,” says Dr. Kay. “Our BANDIT trial will determine if the treatment can protect insulin-producing cells of people recently diagnosed with type 1 diabetes from further immune attack. If it proves successful, production of insulin will be maintained and people with type 1 diabetes will be significantly less dependent on insulin treatment. Making more insulin after diagnosis of diabetes has benefits that are increasingly recognised.”

JAK inhibitors are a type of therapeutic that do what the name says—stop or inhibit the activity of a JAK protein in your body.

It is a bench-to-bedside research project—that has gone from basic research at the laboratory through a clinical trial in people with T1D—that Breakthrough T1D has had a hand in for more than a decade.

“We are very excited to support this trial, led by Dr. Thomas Kay and colleagues,” says Simi Ahmed, Ph.D., director of research at Breakthrough T1D. “We are grateful to Eli Lilly and company for providing the investigational drug, and to our colleagues at Breakthrough T1D Australia for their partnership in launching this trial.”

Preservation of a Body’s Own Beta Cells

The trial aims to recruit approximately 85 participants, aged 12-30 years, who have been recently diagnosed with T1D and will test if baricitinib can slow the loss of insulin-producing beta cells in people with the disease.

Baricitinib is already approved for the treatment of rheumatoid arthritis and is currently in clinical trials for other autoimmune diseases (T1D is an autoimmune disease, too). This is because JAKs are often associated with over-reactive immune systems. Recently, the FDA approved it in combination with remdesivir for the emergency treatment of people who have been hospitalized with severe COVID-19 and whose immune systems are on over drive.

Other JAK inhibitors have been approved for treating blood cancer, which is a cancer of the immune system. This is the first time, however, that a JAK inhibitor is being tested in T1D.

A Reversal of T1D. Wait…What?!?

One might say that T1D can’t be reversed. Well, that’s not true now.

On October 8, a letter to the New England Journal of Medicine revealed that doctors had reversed T1D in a young man. This was a precision medicine treatment that corrects the effect of a mutation of a gene product that is directly activated by JAKs, and he has been off insulin treatment for more than 2 years.

What drug was it? Another JAK inhibitor. (This time, it was ruxolitinib.)

We don’t know whether JAK inhibition will help others with T1D, who don’t have this genetic mutation. However, we do know that cell pathways that involve the JAKs are aberrant in T1D and in many other diseases. We’ll have to see the results of this clinical trial to know.

“Breakthrough T1D remains very hopeful that the results will propel future commercial development of this class of therapies for type 1 diabetes,” says Ahmed.

Stay tuned.

Clinical Trial Information

If you are interested in participating in the BANDIT (BAricitinib in New-onset type 1 DIabeTes) trial, contact the trial coordinator via email at bandit@svi.edu.au or by mobile on +61 3 0450 323 962 in Australia.