Type 1 Diabetes Drug Tzield Under Expedited Review Through New FDA Program

The FDA has accepted for expedited review Sanofi’s supplemental biologics license application for Tzield (teplizumab-mzwv) to delay the progression of stage 3 Type 1 diabetes (T1D) in recently diagnosed adults and pediatric patients eight years of age or older. Stage 3, also known as the clinical stage of the disease, is typically when a diagnosis is made after people start showing symptoms.

Type 1 diabetes is a disease where the immune system destroys insulin-producing beta cells in pancreatic islets. About 2 million Americans have Type 1 diabetes. Tzield is a CD3-directed monoclonal antibody that was approved in 2022 as a therapy for adults and children eight years of age and older with stage 2 Type 1 diabetes to delay progression to stage 3. Stage 2, also called presymptomatic disease, is when blood sugar is abnormal and patients have two or more diabetes-related autoantibodies.

The expedited review is part of the recently announced National Priority Voucher pilot program based on its potential to address a large unmet medical need. The pilot program aims to shorten the review process from what normally takes 10 months to 12 months to between 1 month and 2 months. This program uses a collaborative tumor board-style review process to accelerate approvals.

The sBLA for Tzield is supported by the results from the PROTECT phase 3 study, which were presented recently at the Annual ISPAD Conference in Rotterdam, The Netherlands. The study enrolled 217 patients who were randomized to receive Tzield, and 111 patients were randomized to placebo. Participants received a first course of 12 daily infusions, followed by a second course of 12 daily infusions after 26 weeks.

In the study, Tzield was able to slow the loss of beta cells and preserve beta cell function as measured by C-peptide in children and adolescents aged 8 to 17 years diagnosed in the preceding six weeks with stage 3 autoimmune Type 1 diabetes. C-peptide is a biomarker for beta cell function.

Although the study’s key secondary endpoints did not meet statistical significance, numerical trends favoring Tzield were seen in relevant clinical parameters, including the need for fewer insulin units and a higher in-range.

“These new results build on the findings from multiple studies across different stages of the disease process, further supporting Tzield’s potential to modulate the progression of T1D,” Kevan Herold, M.D., C.N.H. Long Professor of Immunobiology and of Medicine (Endocrinology), Yale School of Medicine and Primary Investigator of PROTECT, said in a news release.

Safety was consistent with previous data, and adverse events include headache, nausea, rash, lymphopenia, leukopenia, and gastrointestinal symptoms. The most common serious adverse event was cytokine release syndrome. In PROTECT, 1.8% of those who received Tzield developed cytokine release syndrome possibly or probably related to Tzield.

An observational extension study following patients for another 42 months is ongoing, Sanofi said.

Tzield’s sBLA is also being reviewed under the accelerated approval program, which allows developers to use a surrogate endpoint that is thought to predict clinical benefit but is not itself a measure of clinical benefit. This program requires a confirmatory study for full FDA approval.

Sanofi officials said a phase 3 confirmatory trial, the BETA-PRESERVE study, was recently initiated and is currently enrolling patients.