The FDA ( Food and Drug Administration ) has approved the Biologics License Application ( BLA ) for Tzield ( Teplizumab-mzwv; Teplizumab ), an anti-CD3-directed antibody, for intravenous use, as the first and only immunomodulatory treatment to delay the onset of stage 3 type 1 diabetes ( T1D ) in adult and pediatric patients aged 8 years and older with stage 2 T1D.
The most common adverse reactions ( more than 10% ) that occurred during treatment and through 28 days after the last study drug administration from the TN-10 study were lymphopenia ( Tzield 73%, Placebo 6% ), rash ( Tzield 36%, Placebo 0% ), leukopenia ( Tzield 21%, Placebo 0% ) and headache ( Tzield 11%, Placebo 6% ).
The progression of type 1 diabetes can be particularly onerous; patients who progress from stage 2 to stage 3 type 1 diabetes can develop diabetic ketoacidosis, which can be life threatening and is experienced by up to 50% of stage 3 patients at the time of presentation.
The onset of stage 3 type 1 diabetes 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.
These complications can cause stress, fear, and anxiety in patients as they work to manage their type 1 diabetes diagnosis and provide perspective on the meaning of a delay in the onset of stage 3 type 1 diabetes.
Teplizumab binds to CD3 ( a cell surface antigen present on T lymphocytes ) and its mechanism is believed to involve partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes.
Teplizumab leads to an increase in the proportion of regulatory T cells and exhausted CD8+ T cells in peripheral blood.
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 premedicating and monitoring for symptoms of cytokine release syndrome ( CRS ); risk of serious infections; decreased levels of a type of white blood cell called lymphocytes; risk of hypersensitivity reactions; the need to administer all age-appropriate vaccinations prior to starting Tzield; as well as avoiding concurrent use of live, inactivated and mRNA vaccines with Tzield. ( Xagena )
Source: FDA, 2022