Teplizumab (sold as Tzield) was recently approved for use in people at-risk of diagnosis for T1D. At risk meaning people who have two autoantibodies and abnormal blood glucose measurements, but not yet requiring insulin injections. However, this phase-III study was testing its effectiveness on people after diagnosis; people in the honeymoon stage. The goal is to get Tzield approved for honeymooners in addition to the current approval for at-risk people.
This was a large study: 328 people, 217 got the treatment and 111 were in the control group. The people were all between 8 and 17 years old, within 6 weeks of diagnosis. They got two treatments with each treatment being 12 days of Tzield infusions. One treatment is 6 months after the other.
Results
The results are good but not great. Perhaps a better way to say it, is that they are scientifically good, statistically significant and all that, but it is not clear how much they will matter to families with T1D.
The key result measured how much insulin a person was generating. During the honeymoon period, it normally drops a lot. In this trial, people who got the treatment did generate less insulin, but not as much less as people who were not treated. And the difference was significant. Untreated people insulin production dropped .21 (pmol/ml), while those who were treated dropped .09. However, the other question is, does this .12 difference really mean anything? They are still loosing the ability to generate their own insulin.
They also measured slightly lower insulin use, and slightly lower A1c numbers, but these were not statistically significant, nor were they clinically significant. Clinically significant meaning important to the people with T1D or their families. For example, a person who injected 4.6 units of insulin with treatment might have injected 5.8 units without. That is a differences, but it is not clear how much it matters to the person doing the injection. The A1c differences were about 0.1%, which is well below the 0.5 difference that is generally considered important.
Press Release: https://www.news.sanofi.us/2023-10-18-TZIELD-R-Phase-3-data-presented-at-ISPAD-shows-potential-to-slow-the-progression-of-Stage-3-type-1-diabetes-in-newly-diagnosed-children-and-adolescents-full-data-simultaneously-published-in-The-New-England-Journal-of-Medicine
Journal Article: https://www.nejm.org/doi/pdf/10.1056/nejmoa2308743
Clinical Trial Registry: https://classic.clinicaltrials.gov/ct2/show/NCT03875729
Discussion
For the company, the big question is: Is this one phase-III trial enough to get approval for an additional population? I don't know the answer, but I suspect we will all find out in 2024. Either the FDA will approve it, or they won't. Once the FDA makes that decision, it will tell us a lot about how the FDA will make future decisions about similar treatments. However, I don't think it is worth guessing about the decision; better to just wait for it.
For people living with T1D, the big question is: Is it worth it? That is a decision every person (or family) must make for themselves. It is a trade off of two 12 day series of infusions so that your body creates more of its own insulin for a longer period of time. However, it is not clear to me how much this will matter in the long term. You will still be injecting insulin, just a little less than otherwise. Many people believe that generating more insulin for longer periods of time will lower the long term bad effects of T1D, and this would be a clear benefit. However, this has never been measured and no one knows if the effect of this treatment is big enough to matter.
One question I'm sometimes asked is "will doctors be able to play around with the dosing to get better results?" My answer to that is yes they will be able to, but I don't think they will, at least not aggressively. Why not? It is an infusion treatment, which is not going to encourage experimentation. Also, the drug sometimes has side effects over the 14 days of infusion (things like rashes and decrease in white blood cells), which is not going to encourage experimentation with higher doses, either. More generally, since the benefit is basically a statistical delay in onset of T1D, if a doctor wanted to experiment, they would not see the results for years, and would only see them in a statistical sense after they had done the experiment on many patients. I just don't see that happening.
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