TN-10 Study Analysis: Expert Perspectives on Key Efficacy and Safety Data

The following is a summary of the video transcript and has been edited for length and clarity.

Goldman: Would you now walk us through the pivotal study of teplizumab, the TrialNet 10 (TN 10) study? [NCT01030861]

Burton: The TN 10 study enrolled first-degree relatives of patients with type 1 diabetes who did not themselves have type 1. They were 8 years old or older and at high risk for type 1, meaning that they had 2 or more autoantibodies detected in 2 blood samples within 6 months. They also had to have evidence of dysglycemia based on an oral glucose tolerance test (OGTT) and to meet several other blood glucose criteria. The primary outcome was the change in β cell function as measured by C-peptide levels. The secondary outcomes were insulin doses, HbA1c, hypoglycemic events, and time in target glucose range.

The initial analysis showed that teplizumab compared to placebo significantly delayed the onset of stage III type 1 diabetes by 2 years (Figure 3. below). In the extended analysis that ran for about 79 months, they saw an additional delay in the time to progression to stage III, of almost 3 years (2.7 years). That’s almost 3 more years before a teenager, maybe a college kid, would need to be on daily insulin. It only takes one time overdosing on insulin after a party.

Goldman: AtPediatric Endocrinology of North Texas you have had experience with teplizumab infusions. What type of outcomes have you seen?

Burton: I have a patient who is a sibling of one of my other patients who has type 1 diabetes and I was seeing her for Hashimoto disease. She started showing dysglycemia when she was 17 years old. We did the teplizumab infusion about 9 months ago and she still does not require insulin. Her blood glucose levels are normal as of the laboratory testing we did a few weeks ago. She's starting college this fall and won’t be starting with an insulin pump. This is just such a relief for these families to not have to worry about their children in a way that families with kids who have full stage III, insulin-dependent diabetes have to worry about them.

I follow her every 6 months and screen with fasting blood glucose level and HbA1c. At home, I have her check her 2-hour postprandial blood glucose once every few weeks.

Goldman: What about adverse events with teplizumab? The rate of lymphopenia in the TN10 trial was quite high.

Burton: Lymphopenia happens in almost everyone and I tell families that means the teplizumab is working. But it resolves quickly. A pruritic allergic-looking rash is common but Benadryl, topical hydrocortisone cream takes care of it. Mild flu-like symptoms, headache, runny nose, also are common but transient.