Today, the U.S. Food and Drug Administration (FDA) weighed the evidence for teplizumab to delay type 1 diabetes (T1D) in at-risk individuals, and the T1D community got a big win: Approved, under the brand name Tzield™! Tzield (teplizumab-mzwv) is the first disease-modifying therapy for individuals at-risk for developing T1D. (At-risk means that they exhibited 2+ T1D-related autoantibodies—antibodies against one’s own self—and their blood glucose is starting to be abnormal, but they have not yet become insulin dependent.)
For the first time in history, there is an approved therapy that addresses the autoimmunity behind T1D—not just the symptoms that it causes in 1.4 million Americans.
Aaron Kowalski, Ph.D., CEO of Breakthrough T1D, celebrated the decision—the first approved therapy that can slow, halt, or reverse the course of the disease—for T1D.
“A delay in the onset of type 1 diabetes will have a tremendous impact on the daily lives of people at risk for diabetes, their families, and the overall health system,” said Dr. Kowalski. “It would free them from the constant burden and stress of blood-sugar 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. That is clinically meaningful.”
Tzield can start to address the stark unmet need for disease-modifying therapies and provide people at-risk for T1D and their families at least without the burden and complications this disease brings. Tzield and multiple potential disease-modifying therapies that Breakthrough T1D has invested research into put us on the critical pathway to finding cures and, one day, preventing T1D entirely.
Breakthrough T1D thanks the FDA for their thorough and thoughtful review of the evidence and data, showing that the benefits outweigh the risks to delay clinical T1D in at-risk individuals.
What It Means for the Community
A delay in onset will be a gamechanger for at-risk individuals. Dr. Cory Wirt has experienced this firsthand. She enrolled her daughter, Claire, who had biomarkers and was at-risk for developing T1D, in a clinical trial for Tzield 7 years ago. Today, she has yet to progress into clinical T1D.
“As a mom, I appreciate 83 months of not checking blood-sugars multiple times per day, worrying about life threatening lows, and balancing my child/teen’s independence with the importance of tight medical control,” said Dr. Wirt. “Not to mention the significant cost of supplies, office visits, and emotional stress. We don’t know how long the effects of the treatment will last, but every day without insulin has been a gift!”
Tracy Olsten is another parent who made the decision to enroll her daughter, Mikayla, in clinical trials for Tzield. “We know Mikayla has the biomarkers,” said Olsten. “We know the probability is high that she will develop T1D in her life. But a little bit more time to live her teenage, young adult, and adult years without injections and finger pokes.”
A Day Decades in the Making
Today’s decision would simply not have been possible without decades of Breakthrough T1D work, from funding discovery research to clinical development to work with regulators. Breakthrough T1D had a hand in the development of Tzield from the very beginning:
- 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 study, that he could prevent autoimmune diabetes with an anti-CD3 antibody (which, later, became a humanized version, Tzield). He has gone on to receive more than 15 grants from Breakthrough T1D and was the lead on the clinical trial that demonstrated that Tzield could delay the onset of T1D 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 (it was called MGA031 at the time). MacroGenics 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—that did a clinical trial of Tzield and identified who is likely to respond to the drug.
- Breakthrough T1D has also been a longstanding and passionate advocate for the Special Diabetes Program (SDP), an NIH program funded by Congress that enabled the creation of TrialNet—the largest clinical network for T1D. In 2010, with NIH, Breakthrough T1D, and the American Diabetes Association funds, TrialNet ran the clinical trial of Tzield in at-risk individuals, led by Dr. Herold.
The Breakthrough T1D T1D Fund made a strategic investment in Provention Bio in 2017 that brought the company into T1D for the first time. That investment has helped catalyze hundreds of millions of dollars toward clinical development, regulatory work, and launch preparation that made this moment possible.
Dr. Kevan Herold is one of the pioneers who began this research. Here are his thoughts on this momentous day:
“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 2 decades ago,” said Dr. Kevan Herold, Yale School of Medicine. “The success of this initial study planted a seed that led to further studies and support from the NIH.
“The recent decision represents a turning point in the field. First, it identifies a way in which an immune therapy to stop the disease process might be combined with cell replacements in those with type 1 diabetes. It also suggests that it is time to more broadly screen to identify those at risk for type 1 diabetes, since now there is a therapy that can change its course.”
The success of Tzield—the first disease-modifying drug for T1D—is something that the T1D community, Breakthrough T1D, and other like-minded nonprofits, companies, consortia, and regulators should be gratified and proud of—but our work to find cures continues full steam ahead. We have multiple cures therapies in the pipeline today whose path to market became a little clearer with this approval. We are moving ever closer to a world without this disease, and Tzield receiving approval is one gigantic step along the way.
