Studies suggest teplizumab may be beneficial treatment for type 1 diabetes

ADA 71st Scientific Sessions

SAN DIEGO — New research presented here demonstrates the efficacy of teplizumab, an anti-CD3 medication, in improving beta cell function and preserving C-peptide levels in patients with newly diagnosed type 1 diabetes.

AbATE study

The phase 2 AbATE study examined whether administering a second course of IV teplizumab 1 year after initial administration could prolong its effects. Kevan Herold, MD, professor of immunobiology and medicine (endocrinology) and deputy director for Translational Science at the Yale School of Medicine, presented the results on 83 patients with type 1 diabetes, 53 of whom were randomly assigned to an intention-to-treat subgroup and 25 to a control subgroup.

“The question was: if you treat patients with two cycles of teplizumab, could you improve C-peptide responses at 2 years? The answer from the AbATE trial was absolutely yes,” Herold said at a press conference.

The study confirmed that patients assigned to teplizumab continued to show improved beta cell function out to 2 years after diagnosis, as compared with participants who were not given any medication. At 2 years, the teplizumab group experienced a 45% decrease in beta cell function vs. a 77% decrease in the control group. In addition, the control group used 57% greater amounts of insulin, on average, that the control group at the end of the study, according to Herold.

“The effect seemed to be the most pronounced from the first course of the drug,” Herold said in a press release from the ADA. “It also seemed to be effective in younger subjects, age 8 to 12.”

Previous trials of teplizumab found that giving a 14-day course to people aged 8 to 30 years who were newly diagnosed with type 1 diabetes preserved beta cell function for 1 year or longer, but the drug’s effects started to wane after 1 year. Herold said the researchers will continue to analyze data to help them compare the benefit of receiving one course of teplizumab vs. two courses.

Protégé study

Nicole Sherry, MD, director of the diabetes center at the Massachusetts General Hospital for Children in Boston, presented 1-year results of the Protégé phase 3 study, a comparison of four regimens of daily IV teplizumab infusions in patients with newly diagnosed type 1 diabetes.

The study compared a 14-day full-dose regimen, 14-day one-third-dose regimen, 6-day full-dose regimen and placebo administered at baseline and at 6 months. Of 763 patients aged 8 to 35 years who were screened, 516 were randomized and 513 were treated with at least one dose of the drug. Ninety-seven percent were followed through the 1-year endpoint. Sherry said it is important to note that twice as many patients were randomized to the 14-day full-dose group to maximize exposure.

Sherry said that the primary outcome — percentage of patients with insulin use less than 0.5 U/kg per day and a composite of that with an HbA1c less than 6.5% at 1 year — did not differ among groups.

“In the 14-day full-dose group, 19.8% met the composite endpoint at 1 year compared to 20.4% in the placebo group; it was about equal,” she said at a press conference.

However, the study did yield some positive results, the researchers said.

“Importantly, exploratory analyses suggest that the 14-day full-dose regimen preserves C-peptide at 1 year (P<0.05). Additionally, 5% of patients do not require insulin at 1 year in the teplizumab group, with no patients off insulin in the placebo group at 1 year (P=.03),” Sherry said. The percentage of patients requiring very low doses of insulin, less than 0.25 U/kg per day, and retaining HbA1c less than 7% was greater with teplizumab at 1 year (P=.006).

Regional differences were noted in the study population, with patients in the US demonstrating a greater treatment effect.

In addition, “we noticed particular benefit in children ages 8 to 11 years. This is an important finding because the management of diabetes in children is very challenging,” Sherry said.

The researchers said patients started treatment especially early in the Protégé study, within 6 weeks of diabetes diagnosis.

Adverse events and serious adverse events were similar between the treatment and placebo groups. The most common adverse event associated with teplizumab was rash (53% vs. 20%).

“Teplizumab has an acceptable safety product profile in this dose regimen,” Sherry said.

The 2-year Protégé study is still underway.

For more information:

• Gitelman SE. Treatment of type 1 diabetes – update on clinical trials.
• Sherry NA. Treatment of type 1 diabetes – update on clinical trials. Both presented at: American Diabetes Association’s 71st Scientific Sessions; June 24-28, 2011; San Diego, Calif.

Disclosure: Drs. Gitelman and Sherry report no relevant financial disclosures.

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