A clinical trial in Stage 2 type 1 diabetes (T1D) patients showed that Tzield delayed the median onset of Stage 3 T1D by around two years – consequently delaying the burdens, complications and risks associated with Stage 3 T1D: such as life-long insulin injections.
“This approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, M.D., director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research, as the FDA announced the green light for the drug yesterday. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”
Delaying symptomatic Stage 3
Over 1.8 million Americans have T1D. Stage 3 patients can develop diabetic ketoacidosis, which can be life threatening and experienced by up to 50% of Stage 3 patients.
Insulin therapy and glucose monitoring are currently the standard of care for treating clinical-stage, or Stage 3 T1D, and are necessary to keep T1D patients alive. The constant monitoring and administration of insulin represents a significant life-long burden for patients.
T1D diabetes usually develops in children, teens & young adults; although can happen at any age. It is less common than type 2 diabetes (around 5-10% of people with diabetes have T1D) and is thought to be caused by an autoimmune reaction with genetics believed to be a factor. Diet and lifestyle habits don’t cause T1D.
T1D typically takes more than a decade off a person's life, and life expectancy is reduced by 16 years on average for people diagnosed before the age of 10.
T1D starts in the body long before symptoms appear: but those with pre-symptomatic Stage 2 T1D have a nearly 100% risk of going on to develop symptomatic diabetes. A blood test can detest Stage 2 T1D.
Tzield (teplizumab-mzwv) is a CD3-directed antibody for patients with Stage 2 T1D: which binds to certain immune system cells and delays progression to stage 3 type 1 diabetes. The drug may deactivate the immune cells that attack insulin-producing cells, while increasing the proportion of cells that help moderate the immune response.
“It cannot be emphasized enough how precious a delay in the onset of Stage 3 T1D can be from a patient and family perspective; more time to live without and, when necessary, prepare for the burdens, complications and risks associated with Stage 3 disease" said Ashleigh Palmer, Co-Founder and CEO of Provention Bio.
“The onset of Stage 3 T1D is a life-changing moment - once insulin-producing cells are no longer capable of maintaining normal glycemic control, this irreversible condition can lead to the need, in just one year, for a patient, 1,460 finger sticks to check blood glucose levels, around 1,100 insulin injections, and experiencing an average of 127 episodes of hypoglycemia,” added Dr. Eleanor Ramos, Chief Medical Officer at Provention Bio.
“These complications can cause stress, fear, and anxiety in patients as they work to manage their T1D diagnosis and provide perspective on the meaning of a delay in the onset of Stage 3 T1D."
Clinical data backing approval
Tzield’s safety and efficacy were evaluated in a randomized, double-blind, event-driven, placebo-controlled trial with 76 patients with stage 2 type 1 diabetes.
Patients randomly received Tzield or a placebo once daily via intravenous infusion for 14 days.
The primary measure of efficacy was the time from randomization to development of stage 3 type 1 diabetes diagnosis. The trial results showed that over a median follow-up of 51 months, 45% of the 44 patients who received Tzield were later diagnosed with stage 3 type 1 diabetes, compared to 72% of the 32 patients who received a placebo. The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo.
“This represents a statistically significant delay in the development of stage 3 type 1 diabetes,” noted the FDA in announcing Tzield’s approval.
The most common side effects of Tzield include decreased levels of certain white blood cells, rash and headache. The use of Tzield comes with warnings and precautions, including but not limited to avoiding concurrent use of live, inactivated and mRNA vaccines with Tzield.
Tzield received Priority Review and Breakthrough Therapy designations for this indication.
Long term benefits
The American Diabetes Association (ADA), a voluntary health organization which aims to improve the quality of life for the over 133 million Americans living with diabetes or prediabetes, welcomes the FDA approval.
“This is an historic moment for all people affected by type 1 diabetes (T1D). The approval of Teplizumab, the first-ever treatment approved for the delay of T1D, is a significant step forward for everyone impacted by this chronic disease,” said Dr. Robert Gabbay, Chief Scientific and Medical Officer for the American Diabetes Association.
“People with T1D require life-long insulin replacement therapy, so to be able to provide an individual with a 2-year delay from the symptoms and burden of T1D is a tremendous accomplishment as we look towards finding a cure. There will likely be long-term benefits for blood glucose management and the reduction or delay of acute and long-term complications. The immeasurable benefits of improved quality of life will be felt not only by those diagnosed with T1D, but also by their families. Today is a great day for the diabetes community.”
Tzield is indicated to delay the onset of Stage 3 T1D in adults and pediatric patients aged 8 years and older with Stage 2 T1D. Tzield injection is supplied as a sterile, preservative-free, clear and colorless solution in a 2 mg/2 mL (1 mg/mL) single-dose vial for intravenous use. The drug is administered by intravenous infusion (over a minimum of 30 minutes) once daily for 14 days.
In October 2022, Provention Bio announced a co-promotion agreement for the US launch of Tzield with Sanofi. Olivier Bogillot, Head of US General Medicines, Sanofi, stated, "This approval is a profound and long-awaited victory for the diabetes community. We look forward to leveraging Sanofi's established infrastructure and expertise in endocrinology to deliver for individuals in need across the US."