The Status of NMOSD Patient Education and the Development Pipeline

Bruce Cree, MD, PhD, MAS

Since 2019, patients with neuromyelitis optica spectrum disorder (NMOSD) have been given a trio of therapeutic options that were approved by the FDA. The first, eculizumab (Soliris; Alexion), was followed by 2 others in due time: satralizumab (Enspryng; Genentech) and inebilizumab (Uplizna; Horizon).

Notably, all 3 therapies work through different mechanisms of action, providing a nice variety for patients and clinicians. Bruce Cree, MD, PhD, MAS, FAAN, clinical research director, UCSF Multiple Sclerosis Center, and professor of clinical neurology, UCSF Weill Institute for Neurosciences, has been treating patients with NMOSD for some time and told NeurologyLive about his experiences with these therapies and the effect that they’ve had on clinical care.

Cree also expounded on the impact that the COVID-19 pandemic has had on getting information out to patients and physicians about these new agents since 2 of the 3—satralizumab and inebilizumab—entered the market during the pandemic’s height while the other—eculizumab—was only available for a short time prior to its inception. This has led to additional challenges in information dissemination and difficulty in patient education efforts. Cree also discussed the standing of the clinical development pipeline in light of these approvals, and what it might take to potentially cure NMOSD.

NeurologyLive: In your experience, how has patient education come along about these new drugs? Does the patient community follow that closely?

Bruce Cree, MD, PhD: There are probably some patients who do follow things closely, but in my personal experience, that's not really the case. The diagnosis of NMO for many patients is still mysterious. It's filled with fear, it's a scary diagnosis to hear about, and there's still a fair amount of misinformation and old information that people can get ahold of. So really closing that gap with these drugs that are FDA approved, and the patients who would be receiving these medications is, in my mind, an enormous unmet need.

Now, how do you close that gap? That's a challenging question. You have to find those NMO patients, and then get information to them. And unlike migraine, or gout, or diabetes, or asthma, where you can see commercials and ads all the time on television, with a rare disease—how do you do that? You can't just put out an ad on network TV for NMO when there are going to be 1 in 50,000 viewers who have the disorder, right? It's going to be a challenge.

There are other strategies to doing this and improving patient knowledge and education is extremely important. The Guthy-Jackson Charitable Foundation has done a lot to do that. But there's still clearly a big unmet need that not even the Guthy-Jackson Charitable Foundation can fully address. What we need is an NMSS-type organization for NMO—NMSS standing for National Multiple Sclerosis Society—where you've got a large organization that that helps promote education and awareness of the disease that acts as a major fundraising and grant-giving institution. We don't have anything really quite like that in NMO.

And I hope that one day the pharmaceutical companies who've invested in these products, and are charging such high rates for their use, will come to the realization that they also need to invest in patient education.

Do you foresee more sponsors making their way into the space, or any additional development happening?

A great question, and I think with these three drugs that are so effective, and are also, generally speaking, quite safe, they are creating a barrier to entry of new for new products because now you can't do a placebo-controlled trial. Anything you do is going to have to be based on a superiority study design, which necessitates a larger sample size and additional costs associated with drug development. Plus, when something is 78% to 92% effective, to get beyond that, you really have to be hitting the ball out of the park. For anti-inflammatory therapies, these are the 3 mainstay treatments that are going to be around for a long time. I do see them gradually taking over more of the market as both providers and patients become aware of their use and begin to make use of these drugs. The off-label therapies will give way to them.

There is an area of research that I think is going to be extremely productive, which is that we think that there may be strategies that where we can effectively cure NMO, not through immune suppressants, but by fixing the break in self-tolerance that occurs with NMO. NMO is not an inherited disease, it's an acquired disease. Something occurs to cause a breach in self-tolerance where patients no longer are tolerant of aquaporin-4 and can develop an antibody response to it. That breach in self-tolerance—we think—we will ultimately be able to correct.

There are multiple self-tolerizing strategies that can promote tolerance for specific antigens. And I do think NMO is going to be one of the first autoimmune diseases in which that strategy is going to be effective and will be hopefully, if not the first, one of the first autoimmune diseases that we can cure. I'm very excited about that.

The interesting thing there with promoting self-tolerance is that we have an antibody that we can measure, and we have T cell responses that we can measure. We could provide a tolerizing treatment to somebody who's clinically stable on therapy, but who still has a T cell response as well as a B cell response, and we can treat them until that immune profile resolves. Then you could ask the question about if we can stop the immune suppressants in that patient and see how they do. Very, very interesting study design. I think that is the direction of the future, and we'll see which product or strategy ultimately is able to reverse that autoimmune deficit in NMO.

Transcript edited for clarity.