Experts in endocrinology share challenges of patient access to type 1 diabetes treatment as well as resources to combat these challenges.
Steve Edelman, MD: As endocrinologists, what’s our role in pediatric or adult diabetes in making and getting teplizumab accessible for families? It’s like anything that you don’t have insurance for: it’s quite expensive. Do you have any ideas along those lines? We don’t work for the company, but there are programs. The company that owns teplizumab hired a third party to help with reimbursement, and there are financial assistance programs. Does anybody have anything to add to that?
Justin M. Gregory, MD, MSCI: Yes, it’s called the COMPASS Navigator program.
Steve Edelman, MD: Thank you.
Justin M. Gregory, MD, MSCI: My experience has been that they’re helpful. But a limited number of centers are able to do this logistically. What we don’t want to happen is a patient isn’t able to get this drug with benefit if they don’t live close to 1 of these big centers. It’s a big undertaking because you’re talking about not a single day but 14 days away from work…. I don’t think we have this figured out. Pediatric oncologists have a better sense of this because they commonly do this. This is why there’s Ronald McDonald House and these kinds of things. This is something we need to think about right now. This ties into the PROTECT study. So far, we’re talking about stage II. Relatively speaking, it’s a small number of patients. It’s not beyond the pale to think that this is going into stage III soon. Then you’re talking about an immensely greater number of patients doing 12 days of immunotherapy.
Schafer Boeder, MD: Or into stage I. As we start to do screening earlier and understand when the optimal time to intervene is, I don’t think we can say that we definitively know. This may be a widened window, potentially in both directions.
Steve Edelman, MD: It has been estimated that there are 300,000 individuals at risk for developing stage 3 in the United States, but they’re hard to screen for. They don’t have any symptoms. But if this or any other therapy gets approved for stage III, it’s going to be like wildfire because as soon as a parent has a child, what do they want to do? What could they do? It’s good that we have a buffer zone to set up these infusion centers.
Schafer Boeder, MD: We’re figuring out how to do this from a structural standpoint. A lot of smart individuals working are on it, but there’s a long way to go in terms of how to logistically put this infusion in place for patients, whether it’s at home or in infusion centers. The onus is shared. We all have to do that work. But if you’re a provider who takes care of patients with type 1 diabetes, and you’re expecting in the future that a patient—or a loved 1 of a patient—will walk into your clinic and be screened as an appropriate candidate for this therapy, there’s a finite window to deploy the therapy. Thinking about how these logistics will work in your own site sooner rather than later is probably worthwhile because it’s a big process. Finding the technical expertise, the individuals to do the infusion, and the monitoring takes a lot of time. Get started on that process. If you’re thinking, “I’m going to use this therapy,” then try to reach out for the resources available.
Linda A. DiMeglio, MD: You referenced that not everybody responded to the therapy. There were certain HLAs, antibodies, and timing. As we rush short immunomodulatory therapies, we’re going to see that it’s appropriate—given that we have a therapy that looks like it’s highly effective and can do a job in some patients—to keep the door open for other sequential therapies and combination therapies because we’re talking about a delay. We’re not talking about a cure of diabetes. I love the phrasing that we need cures, not a single cure, for type 1 diabetes. There’s still going to be a need to innovate, still going to be a need for other treatments. When we think about treating type 1 diabetes, you alluded to stage I. What works in stages I may not work in stage II and III, and the treatment that works for 1 patient may not work for another. Even for an individual, the disease evolves over time and the treatment needs to be tailored. You would never take somebody with cancer and put them on 1 drug, say good luck, and move forward. You’d be monitoring, and that’s something else we need to get better at: monitoring biomarkers’ response over time. If you fail 1 drug, you’d try a different thing. That evolution needs to happen here. I’m not sure how we do that effectively, but it’s something we need to consider in this space.
Steve Edelman, MD: This shows how complicated it is. Having teplizumab available and approved opens the door for other therapies. It’s hard to do these type 1 studies. It takes time, especially screening for stage II and the different combinations. A lot of individuals have said, “Why don’t you give teplizumab once a year?” Studies are underway. This is a good segue. What other therapies out there to delay the progression of type 1? Justin, you go first. Linda, you’re involved in TrialNet, so you can add on.
Justin M. Gregory, MD, MSCI: To frame the studies that are out there, I think of 3 categories. First, we think about antigen therapy. You mentioned the DVT [deep-vein thrombosis] study, where we tried to use insulin as an oral antigen. To this point, in antigen therapy, I haven’t seen great progress, but that’s the area where they’re thinking about different ways of delivering antigen. The idea is that by delivering antigen, you’d bring about a tolerance for that antigen. The second category is immunotherapies. We’ve talked about teplizumab a lot, but other immunotherapies have garnered attention. Abatacept comes to mind. It’s another immunomodulatory agent that influences the way T-lymphocytes stimulate one another. A recent abatacept study came out in which it was initiated in stage I. There was some hope that it would prolong and bolster C-peptide production. It didn’t do as well as I had hoped it would.
The thought becomes, what if you combine these therapies? I put that into a third category. The idea that a single immunomodulatory agent working on 1 antigen is going to bring about long-lasting tolerances doesn’t make sense. Could there be synergistic relationships? As Linda was talking about, what happens if you give a second dose of this? Conceptually, it makes sense to combine things like abatacept with teplizumab to promote longer-lasting immune tolerance. That’s what we’re going to see in the future. Now that we have teplizumab, trials will be teplizumab plus placebo vs teplizumab vs something else. We’ll start to see how we can improve on this first drug that’s on the market.
Linda A. DiMeglio, MD: There’s 1 big challenge we’re going to encounter there, but I’m not 100% sure. We’ve referenced the 14 days or 12 days of infusions, and they need to take off work. It’s not that we didn’t identify more patients who were eligible in [TrialNet] TN10. Some patients chose not to do it because they were worried about the drug. They didn’t know if it would be effective. It was a placebo-controlled trial. Some patients couldn’t take the time off or didn’t want to.
Another issue we’re going to hit in these comparator trials is what if patients don’t want teplizumab? Will there need to be teplizumab plus placebo, teplizumab plus drug, and then a drug-only arm to accommodate that? I’m not sure. That complicates the trial design even further because you need patients opting to go into 1 group or the other. We’re going to need good statisticians and trial designers to help us.
Steve Edelman, MD: It’s hard for me to fathom that someone would say, “I don’t want my child to get it or my first-degree relative because I have to work.” It emphasizes the point that we have to help our patients who are candidates for it to have accessibility.
Linda A. DiMeglio, MD: I laugh in part because there was 1 patient in Indiana who was potentially interested. He had a young family at home, and he was keen to come. But his family was like, “You can’t be gone for 14 days. There’s too much going on.”
Steve Edelman, MD: Those are real issues.
Linda A. DiMeglio, MD: It was a huge issue. It was hard because you have a limited window to get the drug—you have to be not yet stage III and not reverted to stage I.
Transcript edited for clarity.