Teplizumab Approval Expands to Early Type 1 Diabetes

The FDA expanded the approval of teplizumab (Tzield) to include pediatric patients 8 years and older who have recently been diagnosed with stage 3 type 1 diabetes, the clinical stage where hyperglycemia symptoms emerge and insulin therapy is needed.

An anti-CD3 antibody, teplizumab is indicated to delay the decline of insulin production and is believed to work by deactivating the immune cells that attack insulin-producing beta cells while increasing the proportion of cells that help moderate the immune response.

The new indication was granted under the accelerated approval pathway primarily based on the phase III PROTECT study, which randomized 328 patients with stage 3 type 1 diabetes ages 8 to 17 years to either intravenous teplizumab or placebo infusions on top of standard-of-care medicines. Patients needed to have been diagnosed within the prior 6 weeks and have working beta cells at enrollment.

Two 12-day courses of teplizumab given 6 months apart resulted in 59.3% less loss of beta-cell function, as shown by higher stimulated C-peptide levels at week 78 compared with placebo (least-squares mean difference 0.13 pmol/mL, 95% CI 0.09-0.17, P<0.001).

The most common side effects included vomiting, rash, increased liver transaminase, and headache.

As a condition of accelerated approval, confirmatory data showing clinical benefit may be required for continued approval of the indication.

Teplizumab is also approved in adults and children as young as 1 year with presymptomatic type 1 diabetes (stage 2) who have pancreas-targeting autoantibodies and abnormal blood glucose in order to delay progression to stage 3 disease.

The drug is contraindicated in patients who are immunocompromised or have active viral infections, and the drug’s labeling includes a boxed warning regarding serious, life-threatening cases of viral reactivation, including Epstein-Barr virus and cytomegalovirus. Testing is recommended prior to starting.

Cytokine release syndrome has also been reported with teplizumab, which typically occurs within the first 5 days of treatment. Symptoms include fever, fatigue, muscle and joint pain, nausea or vomiting, and increased liver enzymes.

Teplizumab is also associated with leukopenia, lymphopenia, and neutropenia, which can increase the risk of certain infections.