The U.S. Food and Drug Administration (FDA) announced Thursday it approved a new drug that “can delay” the onset of stage 3 type 1 diabetes, which is the symptomatic stage of type 1 diabetes.
The drug, teplizumab-mzwv, is to be used to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older, who currently have stage 2 type 1 diabetes, the FDA announced.
Made by Provention Bio, in partnership with Sanofi, the new drug will be marketed in the United States under the brand name Tzield.
It is administered by intravenous infusion once daily for 14 consecutive days.
Tzield does not prevent or delay type 1 diabetes, which can appear at any age, but most commonly among children and young adults. This stage is not symptomatic.
Type 1 diabetes occurs when the beta cells that make the insulin hormone is destroyed. This causes the pancreas—where the beta cells reside—to lose the ability to make insulin. Insulin acts to transport glucose out of the bloodstream and into the body’s cells to provide energy for the body while keeping blood sugar levels stable.
People with type 1 diabetes have increased blood glucose levels and require multiple insulin doses to survive. They must also monitor their blood glucose levels closely.
The FDA says Tzield “binds to certain immune system cells and delays progression to stage 3 type 1 diabetes.”
“Tzield may deactivate the immune cells that attack insulin-producing cells, while increasing the proportion of cells that help moderate the immune response,” per the agency.
“TZIELD 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,” Eleanor Ramos, chief medical officer at Provention Bio, said in a statement. “TZIELD leads to an increase in the proportion of regulatory T cells and exhausted CD8+ T cells in peripheral blood.”
Assessing Safety and Efficacy
The drug’s safety and efficacy were assessed in a randomized, double-blind, event-driven, placebo-controlled trial called the TN-10 Study. It included 76 patients with stage 2 type 1 diabetes.
Patients randomly received Tzield or a placebo once daily over the course of 14 days. According to the results, 45 percent of the 44 patients who received Tzield were later diagnosed with stage 3 type 1 diabetes compared to 72 percent of the 32 patients who received a placebo.
The median follow-up time was 51 months. The midrange time from the start of the trial to stage 3 type 1 diabetes was 50 months for patients who took Tzield, compared to 25 months for those to took a placebo, which is a “statistically significant delay,” the FDA stated.
Side Effects
Common side effects include decreased levels of certain white blood cells—lymphocytes and leukocytes—as well as rash and headaches.
The label of the drug advises monitoring for symptoms of Cytokine Release Syndrome (CRS), a condition that “occurred in TZIELD-treated patients during the treatment period and through 28 days after the last drug administration.” It also advises to “premedicate with antipyretics, antihistamines and/or antiemetics” prior to treatment with Tzield.
Other warnings and precautions linked to the drug include the risk of serious infections and hypersensitivity reactions.
The label also advises physicians to “Administer live vaccines at least 8 weeks prior to treatment. Live vaccines are not recommended during treatment, or up to 52 weeks after treatment,” because the safety of immunization with live vaccines in Tzield-treated patients has not been studied.
It also advises physicians to “Administer inactivated (killed) vaccines or mRNA vaccines at least 2 weeks prior to treatment,” adding that inactivated vaccines “are not recommended during treatment, or 6 weeks after completion of treatment.”