New Treatment Landscape in MS — Preventing Long Term Disability Through High Efficacy Treatments in Early MS - Episode 14
Key opinion leaders in MS provide closing thoughts on the future of MS treatment including digital therapeutics, new generics, and pipeline drugs on the horizon.
Neil Minkoff, MD: I’m going to open it up and call on each of you to say a few words about what you think the future is and a little about what we can do to try to stimulate the use of higher-efficacy medications earlier in the treatment paradigm. Dr Leist?
Thomas Leist, MD: Stimulation of higher-efficacy medication means they’re available as a first-line treatment. From that point of view, the discussions we’re having are important. As I’ve mentioned perhaps 2 or 3 times, there’s a window of opportunity early in the disease where we can categorically change the trajectory of a patient, where a disease could potentially be disabling, but it may change if we arrest it early on. In certain aggressive patients, it may even include therapies we haven’t talked about, like BMT, or bone marrow transplant.
It’s also very important to understand that we have to transition to a more quantitative assessment of how we assess patients. When I look at the MRIs and say, “This MRI looks about the same as the last 1,” that may be not good enough. In the same way, we potentially have to transition to more quantitative assessments of patients in the clinic.
Ultimately, we may come to a point where MS [multiple sclerosis] approaches something that’s more aligned to a picture, like in oncology, where we have ways to identify patients who are going to respond to a therapy and patients who are going to have a much worse course. That’s above and beyond what we have at this point in time. We may also identify different classes of patients. We’re not yet there. That’s in part where all the frustrations arise from, that it’s a little vague. Unfortunately, right now, MS is a big tent, and there are patients with extreme presentations of all these.
As we embark into the generalization of the MS treatments, where the first-line medications no longer enjoy the proprietary involvement, it’s important that we aren’t stepping back, essentially forcing this vulnerable population of members in plans that step through medications that potentially will leave them with avoidable disability. The rewarder may be that perhaps legislation can be prevented because the disability consortia in the different states are powerful and will reach out to ensure that the patients are protected.
Neil Minkoff, MD: Dr Ross?
Nancy Ross, PharmD, BCACP, MSCS, CSP: I’d appreciate it if payers could be flexible. I know that there are committees that meet and discuss formularies and what should be on the formulary and isn’t. It seems like every time a new medicine is released, it gets shuffled to the back. I understand that there are a lot of other monetary discussions that go on behind the scenes, but payers have traditionally left their core medicines as their primary, and everything else gets ranked as a secondary or, “Have you failed our favorite agents before we try these new cool ones?” I’d like them to be able to look at the data and be a little more flexible with what they can offer patients.
At the same time, when we’re asking for a consideration for these patients—waiting 30, 60, or 90 days for an appeal for a patient who’s trying to go on Tysabri, Mavenclad, or something that needs to be started quickly, to not miss the window that Dr Leist and Dr Okuda have been talking about is harmful. I need an answer quickly. Trying to mail an appeal, fax an appeal, fax an appeal to a fax that doesn’t work—it seems like there are some barriers that payers have an opportunity to fix so that we can get a decision quickly and then adjust quickly. Our patients are left in limbo for way too long while this process works itself out.
Neil Minkoff, MD: That’s why we recently went to Pony Express. Dr Lopes?
Maria Lopes, MD, MS: It’s certainly an exciting time to be in MS. At the same time, payers are reacting to the fact that new products are coming to the market. Nancy is absolutely right. As they go through our P&T [pharmacy and therapeutics] process, many times they start off as nonpreferred. There’s a real opportunity to redefine what excellence in MS looks like. Absent the thought leaders doing that, you’re seeing payers take charge, which is really unfortunate, because there’s a cost to failure for everyone. My wish list is that we start to think about the role of these treatments. Absent biomarkers, how do we determine what choices we need in the frontline setting to be able to satisfy patient choice and provider choice?
We’re in a world where affordability is a real issue in the United States, and I don’t think the clock is going to turn back on that. My plea is that we start to develop some consensus around the approach as it could help patients and also help providers at different levels manage to a higher level of consistency, as if the patient is going to an MS center of excellence. We’re also seeing apps play a bigger role as we think about function, cognition, and this trajectory of what patients are experiencing, to redefine and perhaps intervene earlier in terms of the appropriate treatment, or switch to the appropriate therapy.
And then finally, the crowding. We talked about generics, so clinical differentiation. Real-world data are going to continue to be paramount as payers understand if there really is a clinical differentiation. Finally, education is important: education for payers and patients in terms of shared decision-support tools so that the right decisions are being made with the right balance of clinical efficacy and safety, so we can all achieve the better outcomes we want to achieve. You’re not going to reverse disability, so what can be done to really enhance patient care? We didn’t talk about depression. Even in the consistency of the approach and the comprehensive approach, these patients have multiple medications. Many of the patients are depressed, which leads to all sorts of other issues in terms of noncompliance. How can we do a better job in terms of comprehensive care?
Neil Minkoff, MD: Dr Okuda, take us home.
Darin Okuda, MD: I’ll take a different approach. The future is going to be filled with more generics. By that time, we’ll probably have our 37th dimethyl fumarate, which will really be helpful—not so much. We can expect more generics for sure. I hope there will be a move toward how internists deal with hypertension. When I was in medical school, there was a [Sixth Report of the] Joint National Committee. They’re probably on 15 or something already. It’s great because they stratified it by race and ethnicity, and it had ideal therapies whether you’re Black or African American, like calcium channel blocker or ACE inhibitor. Or if you’re old and you had isolated systolic hypertension of the elderly, which is pretty inappropriate for 2021, there are recommendations for you. There needs to be something like that, because as a group of MS specialists, if we can’t necessarily pinpoint ideal therapies for a given patient’s journey with MS, we can all agree that there are vast differences when you look at Whites vs non-Whites. Although I don’t think payers will get to that point—maybe genomic analysis will be as cheap as getting a CBC [complete blood count] in the future—that may help because a payer can then use a given algorithm to authorize the use of a high-efficacy treatment.
Beyond that, payers will develop more algorithms that will mirror some of what our European colleagues have experienced. If someone has contrast-enhancing lesions within the spinal cord, or something else that could be used as criteria for allowing the use of a high-efficacy agent first-line, that would be great. I don’t think prescription digital therapeutics [PDTs] will gain a lot of traction. It’s very provocative. I lead the neuro-innovation program here [at the University of Texas Southwestern Medical Center]. From my learnings, it needs to replace something that’s of higher cost unless it can save the system money. Its value really is replacing something that’s of higher cost. That’s its immediate value, so I don’t see that coming into play.
I know that Pear Therapeutics had the first PDT that was for substance-use disorder, in which many millennials felt as if conversing online and doing cognitive behavioral therapy on an iPhone was more convenient and better than seeing a person face-to-face. For some of the other tools that we’ve helped develop, we’ve been challenged by a variety of things. With some of our next-generation work, we may be able to provide some solutions to existing hurdles. Unfortunately, this disagreement, lack of an algorithm, or lack of a model for effective care is going to continue. I’m going to predict that.
The most exciting treatment that’s emerging—maybe Tom will agree or disagree—are the BTK inhibitors, and there are a lot of them: EMD Serono Merck with evobrutinib, SAR442168 by [Sanofi] Genzyme, fenebrutinib by Genentech, even TG Therapeutics with 1, Novartis with 1, and Biogen with 1. There are more therapies, more mechanisms of action, but the hope is that payers will be not just flexible but more dynamic by allowing for the use of other treatments that are more inexpensive, so the health care cost to the system as well as to the consumer isn’t super-robust. What does that look like? Something provocative like free leflunomide for you, even though monthly cost is as cheap as $13 or $18 for a 30-day supply, that then gets metabolized to teriflunomide. Or something else, like rituximab in a different formulation or different dose that patients can get at a low cost.
But where I would like to see our field head toward quickly is race and ethnicity stratification, because that’s 1 aspect of care where all MS specialists would have an agreement. We didn’t study these people in a robust fashion in our pivotal trials, because a lot of it is done in Eastern Europe these days, but we know that their disease course, based on existing data, are costly to the people, their families, and the system. That’s 1 low-hanging fruit that can be achieved, rather than having this argument of “No, we should use Lemtrada first vs Mavenclad or Tysabri or Ocrevus.” Moves in that way will get us to where we need to be rather than having an algorithm, like the cancer world, where their lives are easy because they have a lot of biomarkers and people die. For us, you get pinned, you get hurt, and you have to live with that disability for a long time, but you’re still alive. It’s tough to capture that in whatever shape or form that’s nonvideo. When it’s being reviewed by people on your side of the table. It’s very different from saying “Someone died.” I’ll stop with that, Neil, but those are a few thoughts from me.
Neil Minkoff, MD: That was incredible. I want to thank everybody. We’ve gone a little over time, and I’m appreciative of everybody’s patience. I want to thank everybody for participating and for how robust our conversation was. I want to let the viewing audience know how much we appreciate them coming in and being part of our conversation. We hope that everybody found this AJMC® Stakeholder Summit panel discussion to be useful, informative, and something they can refer back to. Thank you very much.
Transcript edited for clarity.