May 27, 2021
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Nina Zeldes, a senior fellow at the center. We analyze scientific data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.
Let’s focus on the data.
Let’s first look at efficacy. FDA scientists note substantial problems with the study sample. There were over twice as many adult patients in the teplizumab group as in the placebo group. Since the expected rate of progression to Type 1 Diabetes is slower in adults than children, this could have biased the data in favor of the drug. Also, the patients receiving the drug had a lower baseline BMI z than those receiving the placebo. Since those with a higher BMI z are at a higher risk of progression to Type 1 Diabetes, this imbalance in BMI z could also have biased the results in favor of the drug.
These study shortcomings are even more worrisome since the sample was small; only 44 patients took the drug in trial TN-10. This is a VERY small sample for a drug that may potentially be given to a large patient population. And more than 97% of those patients were White, making it impossible to know if the drug has benefits for non-White patients who would be likely to use them. Shouldn’t the lack of non-White diabetes patients be unacceptable to you and to the FDA?
Now let’s talk about safety. Most of the safety data are based on patients newly diagnosed with Type 1 Diabetes, not the proposed indication of those at high risk. As FDA points out, there are substantial differences between patients with Type 1 Diabetes and those at high risk. In addition, the drug has the potential to cause immunosuppression, which could increase the risk of infection. In fact, in the full safety sample, serious adverse events of infection occurred in 3.4% of patients given the drug, compared with 2% of placebo patients. There was also a notable difference in diabetic ketoacidosis between those given teplizumab and those given placebo, with 18 patients in the full safety sample for the drug vs 1 placebo patient in that same sample. We agree with FDA scientists that this difference is unlikely to be due to chance.
One more thing: The Kaplan-Meier data show that the main benefit was that fewer patients progressed to Type 1 Diabetes in the first year. The drug did not have significant benefits after that. That’s a very modest benefit, and therefore isn’t better data worth waiting for –based on larger, more diverse samples of at-risk patients? Please keep these issues in mind as you vote today.
The FDA Endocrinologic and Metabolic Drugs Advisory Committee voted (10 yes, 7 no) that there is sufficient evidence of benefit to outweigh the risk of teplizumab.