The U.S. Food and Drug Administration (FDA) has approved teplizumab, marking a historic milestone as the world's first disease-modifying therapy for type 1 diabetes. The groundbreaking immunotherapy has demonstrated the ability to delay disease onset by an average of three years in individuals at high risk of developing the condition.
Mechanism and Clinical Significance
Teplizumab is a monoclonal antibody that specifically targets and weakens the immune cells responsible for destroying insulin-producing beta cells in the pancreas. By addressing the autoimmune root cause of type 1 diabetes, the drug represents a paradigm shift in treatment approach.
"This decision represents a turning point in the field," said Professor Kevan Herold, a JDRF-funded researcher who has been developing teplizumab for nearly 30 years. "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 of type 1 since now there is a therapy that can change its course."
The FDA approval allows teplizumab to be prescribed to people aged eight and older who do not yet have type 1 diabetes but are at high risk of developing the condition. This preventive approach could transform how the disease is managed.
Clinical Trial Results
The landmark trial that led to FDA approval involved 76 participants aged between eight and 49 years who were identified as high-risk for type 1 diabetes. Those who received teplizumab were significantly less likely to develop the condition during the study period compared to those given a placebo. For those who did eventually develop type 1 diabetes, diagnosis came approximately three years later than in the placebo group.
This delay is particularly meaningful for children approaching adolescence, as it allows the pancreas to grow to adult size, potentially leading to better long-term outcomes. Additionally, the treatment may help prevent diabetic ketoacidosis (DKA), a potentially fatal complication that affects one in four children in the UK at diagnosis.
Beth Baldwin, whose son Peter died of DKA at age 13, emphasized the significance: "The potential for a ground breaking new drug to delay the onset of type 1 diabetes will be life changing for so many. The ripple effect this will have will improve diagnosis outcomes and even buy precious time whilst the search for a cure is ongoing – a hopeful reality in our lifetime."
Development Journey and Research Support
The development of teplizumab represents decades of collaborative research, with JDRF playing a pivotal role in funding initial exploratory research, trial recruitment networks, and clinical trials.
"The story with the clinical use of teplizumab began with a JDRF grant to support a trial in patients with new onset type 1 diabetes more than two decades ago," Professor Herold explained. "The success of this initial study planted a seed that led to further studies and support from the National Institute of Health. Over the years the payback on this initial investment has been enormous."
Karen Addington, CEO of JDRF UK, added: "This landmark approval is tremendously important and we, JDRF, are proud to have funded the research into teplizumab from its start nearly thirty years ago. The world now has a drug which is proven to effectively tackle the root causes of type 1 diabetes, delaying the onset of the condition and slowing down disease progression."
Implications for Screening Programs
The approval of teplizumab underscores the importance of screening programs to identify individuals at risk of developing type 1 diabetes before symptoms appear. With a simple blood test, it's possible to detect early signs of immune attack against pancreatic cells, opening a window for preventive intervention.
Professor Colin Dayan, who leads the UK Type 1 Diabetes Immunotherapy Consortium, noted: "This is very exciting news and a key first step in transforming how we care for type 1 diabetes. The introduction of this treatment adds weight to the value of screening for type 1 diabetes. This could prevent up to a thousand people a year from having emergency hospital admissions to start insulin."
A UK-first trial called ELSA (EarLy Surveillance for Autoimmune diabetes), jointly funded by Diabetes UK and JDRF, is currently screening 20,000 children aged three to 13 years to assess their risk of developing type 1 diabetes. This initiative aims to establish the groundwork for routine, widespread screening that would be essential for identifying individuals who could benefit from teplizumab.
Regulatory Status in the UK
While teplizumab has been approved in the United States, it remains under review by the UK's Medicines and Healthcare products Regulatory Agency (MHRA). The drug has received an 'Innovation Passport' under the 'Innovative Licensing and Access Pathway,' designed to accelerate access to promising new medicines in the UK.
This special status means the MHRA will expedite its assessment of teplizumab, with involvement from other key organizations like the NHS and the National Institute for Clinical Excellence (NICE) from the beginning of the process. Though exact timelines for UK approval remain uncertain, the FDA's decision represents a significant step forward.
Future Directions
Beyond its current application in preventing type 1 diabetes, teplizumab is also being investigated for newly diagnosed patients to protect remaining beta cells. Researchers envision that immunotherapies like teplizumab might eventually form part of a comprehensive cure strategy, potentially working alongside beta cell replacement therapies to restore normal insulin production.
The Type 1 Diabetes Grand Challenge, a £50 million partnership between Diabetes UK, JDRF, and the Steve Morgan Foundation, is investing in promising treatments to accelerate breakthroughs and advance the search for a cure.
As Professor Dayan concluded: "Identifying these people will also allow much more rapid testing of other treatments in addition to teplizumab so that we can delay the need for insulin for many more years. Ultimately, I hope it will lead to needing insulin to treat type 1 diabetes in childhood being a thing of the past."
