Empowering Progress: Teplizumab's FDA Approval and Mechanism of Action in Delaying T1D Progression

EP: 1.The Landscape of Diabetes: Unveiling Geographical Disparities and the Role of Prediabetes

EP: 2.Deciphering Diabetes Onset: The Crucial Role of B Cells and Diagnosis Considerations

EP: 3.Navigating the Burden of Diabetes: Screening Recommendations and Insights from Real-Life Experiences

EP: 4.Strategies to Prolong T1D Stage Progression: Impact of Diabetes Ketoacidosis and Potential for Extending Insulin Independence

EP: 5.Type 1 Diabetes Antibody Screening: Keys for Early Intervention and Risk Determination

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EP: 6.Empowering Progress: Teplizumab's FDA Approval and Mechanism of Action in Delaying T1D Progression

EP: 7.Navigating Teplizumab: Dosing, Infusion Process, and Patient Experience in Delaying Late Onset Diabetes

EP: 8.Key Takeaways and Clinical Pearls for the Utilization of Teplizumab

The following transcript has been lightly edited for clarity and style.

Dr. Jennifer Goldman: Are you aware that type 1 diabetes progression through different stages can be delayed? I can't even believe I can ask that question right now. And so, it's- It brings so much hope. So, 62% said yes. So now spread the word. Tell everybody. How familiar are you with teplizumab? So, what do you think? Are you familiar with teplizumab? Is the potential intervention for delaying from stage 2 to stage 3, everyone? So, 54% was not familiar. So thank you for being here and making sure that you become familiar, and please teach other people too. So clearly, a pivotal milestone when the first agent was approved for type one diabetes at high-risk individuals. And so it was first approved, and that's for eight years old and up. Right? You did the trials, right, Dr. Latif? So eight years old and up for now, right?

Dr. Kashif Latif: Yes.

Dr. Jennifer Goldman: So did you want to talk a little bit about the mechanism of action, Dr. Latif?

Dr. Kashif Latif: Kent is the pharmacist and he needs to.

Dr. Jennifer Goldman: Kent. Yes, Dr. Stoneking.

Dr. Kent Stoneking: I'm up on that one. Thanks. So by binding CD3, these anti-C3 antibodies, teplizumab now being the one that's commercially available shifts the proliferation of T cells toward the proliferation preferentially of T regulator cells. And it shifts that balance away from proliferation of CD4 and CD8 T cells, the CD4 being the setup for the CD8, which directly impact the beta cells in the pancreas and cause beta cell destruction and decline of insulin production. So by shifting that balance towards T regulator cells and away from the CD4 and CD8s, we mitigate the risk to the destruction of the beta cells and preserve beta cell function for a longer period of time.

Dr. Jennifer Goldman: Excellent. How stupid of me as a pharmacist to not ask the pharmacist. So the TrialNet, TN-10 study schema was for those over eight years old, with that change in beta cell function was the primary outcome. And do you want to comment a little bit on the results of that before we talk about adverse effects in dosing and how to infuse in our remaining 10 minutes?

Marianne Briggs: So we found with the study that the teplizumab was delaying going from stage two to stage three compared to the placebo. So it's showing that we can delay needing full insulin. And even if it's just two years of life that we push that off, that's two years that a kid gets to be more of a kid or now somebody gets two years of their life. That's worth it to me.

Dr. Jennifer Goldman: Would you say it gives the family opportunities to prepare too, right?

Marianne Briggs: Absolutely.

Dr. Kashif Latif: We have short time, but I do want to add something. You know what, the insurance companies are very intuitive. This would not have been approved or paid for by the insurance companies if this was not worth it financially. So that's one aspect. Now, imagine emotional, which I have taken a lot of time already, but if we talk about that, that is a huge prospect. So this makes sense at every level.

Dr. Jennifer Goldman: So the extended analysis Marianne was about 79 months out. Yes? And a further delay was seen a 2.7 year delay. So I think the future is hopeful and who knows what's going to happen with the ongoing studies. What about, you did the clinical trials, you all are working with patients, Marianne, you did also. Can you just mention what is significant here? Because when you see 73% lymphopenia sounds really bad and scary, but could you put it into perspective for us, please?

Marianne Briggs: Don't be scared. We all were, I was very nervous in the beginning, but we didn't have to stop the infusion for any patient during the clinical trials. We did not have to stop it for the patient that we've infused already, we did not have to stop it. We are aware of it on the front end so you know what to look for, and they do fine. And so I think the major thing is don't be scared.

Dr. Kashif Latif: It is transient. You see that with dose escalation in the day one to three, and then after that it plateaus and it just stabilizes. So again, to what Marianne said, do not be scared. And as resource for everybody and if somebody's infusing, there's a question, we are here for you.

Dr. Jennifer Goldman: Do you know if there's an ongoing study with trial trying teplizumab in younger earlier, if that's ongoing?

Dr. Kashif Latif: Yeah. So trials are ongoing, and the other trials that are ongoing are with the combination therapy and repeat infusion. So there's a lot of immunotherapy out there that we have. So if we can offer somebody an FDA approved therapy by 2.7 or close to three years, and if in the next one or two years something else gets approved or a new combination gets approved. That's what Marianne and Jennifer you talked about earlier, is that we can keep pushing this [00:48:00]-

Dr. Jennifer Goldman: We can buy time.

Dr. Kashif Latif: Absolutely.