Leslie Harrold, MD, MPH, CorEvitas, LLC, Waltham, MA; Michael Levy, MD, PhD, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Brian Weinshenker, MD, Mayo Clinic, Rochester, MN, discuss the establishment of the prospective, observational SPHERES registry to collect real-world longitudinal data from patients with neuromyelitis optica spectrum disorder (NMOSD). Rapid progress in recent years has seen three new agents become approved for the treatment of NMOSD in the US: eculizumab, satralizumab, and inebilizumab. There is now a valuable opportunity to follow patients in the real-world, to better understand NMOSD and to collect data that can inform clinical practice. In this interview Dr Harrold, Dr Levy, and Prof. Weinshenker outline the details of the registry and comment on the value of real-world longitudinal data. SPHERES aims to enroll 800 patients and collect evidence that can inform exploration of disease natural history, patterns of care, and clinical outcomes including treatment effectiveness, safety, and patient experience. This interview took place at the ACTRIMS Forum 2022 in West Palm Beach, Florida.
For more information about participating in the SPHERES registry:
Email: [email protected]
Phone: (508) 408-5426
Transcript (edited for clarity)
Brian Weinshenker, MD (00:06):
Today, we’re going to be talking about the CorEvitas SPHERES Registry done in collaboration with The Guthy-Jackson Foundation about neuromyelitis optica or NMO spectrum disorder as it’s currently known. This is a condition that really has been perceived as a unique disease in the last two decades, and we’ve learned quite a bit about it. But along with our learning, things have evolved...
Brian Weinshenker, MD (00:06):
Today, we’re going to be talking about the CorEvitas SPHERES Registry done in collaboration with The Guthy-Jackson Foundation about neuromyelitis optica or NMO spectrum disorder as it’s currently known. This is a condition that really has been perceived as a unique disease in the last two decades, and we’ve learned quite a bit about it. But along with our learning, things have evolved. We’ve become better at diagnosis and have expanded the spectrum of the disease, and all of these things result in changes in how we understand the disease and a need to better characterize the disease in terms of its manifestations, its course, and natural history. This has led to a need for gaining real-world experience.
Brian Weinshenker, MD (01:09):
Another important thing has been major changes in the way we treat this disease. We have recognized that different treatments are required than used for multiple sclerosis, and now we have a number of new treatments. My colleague, Dr Michael Levy is going to talk to you a bit about those treatments. Michael.
Michael Levy, MD, PhD (01:30):
Thank you, Brian. It is great to be here and to talk about these three new treatments. These were all trialed in international placebo-controlled studies that all launched around the same time in 2013, 2014. The first drug that started the trial was eculizumab, a terminal complement inhibitor that was thought to be useful in preventing the complement-mediated damage in the spinal cord that you see on the pathology of NMO tissue that’s been targeted by the immune system. This trial enrolled patients who were aquaporin-4 seropositive only, and that’s different from the other two studies. They also sought to enroll patients who had more active disease, two attacks in the past year. They showed that eculizumab is very effective in preventing relapses, a total reduction in the risk about of 94% compared to placebo, and the placebo group was allowed to use background therapy.
Michael Levy, MD, PhD (02:42):
The second trial that launched was satralizumab, an IL-6, interleukin-6 receptive blocker, and they did two separate studies that have been for the most part combined in terms of analysis. There was one study in the world outside of the United States that used a background placebo treatment like azathioprine, mycophenolate, and then there was the arm in the United States that was pure placebo. But they were still relatively similar enough that we combined the data. If you look only at the seropositive patients in a comparison to eculizumab, for example, the reduction in risk of relapse was somewhere around 75%, which is also very good.
Michael Levy, MD, PhD (03:25):
Then the third study to launch was inebilizumab, a CD19 B-cell depleting drug that targeted a few more pre-B-cells and a few more plasmablasts and short-lived plasma cells compared to rituximab. Rituximab, we’ve been using off-label for a long time, so there was comfort with using another B-cell depleting drug. This one proved to be about the same as rituximab in terms of our observation of rituximab that about 77% risk reduction just by depleting B-cells with inebilizumab.
Michael Levy, MD, PhD (03:58):
All three drugs were for the most part safe. There were no major safety signals that we’re worried about, especially compared to the risk of a relapse in NMO, which we know is devastating. So all three drugs have now been approved in the United States and are seeking approval worldwide. Our patients who are newly diagnosed are for the most part using these new FDA approved drugs. Some of the patients who’ve been on rituximab or other therapies prior to their approval have been considering switching over. So this longitudinal repository allows us to see how patients are doing on both the older drugs and the newer drugs.
Leslie Harrold, MD, MPH (04:41):
Thanks. I’ll jump in. So I’m Leslie Harrold. I’m from the CorEvitas company. We specialize in developing these autoimmune registries and really building upon the data to inform clinical practice. So when you have patients who are part of a clinical trial, clearly it’s a very select subset of patients, the more severe patients and often not with a range of comorbidities. The value of real-world data is that you can look at patients who you’re much more commonly to see in clinical practice. They have the range of disease activity, they have a range of comorbidities. So in that way, we can look at the natural history of the disease, the effectiveness of the medications, the safety of medications, and also better understand the patient experience. The plan is to get sites on board, we would gather data from both physicians and their patients. Then in that way, we would follow them over time to see how they are doing and be able to assess sort of more long-term how they’re doing in typical clinical practice.
Brian Weinshenker, MD (06:02):
The idea is that this is going to be a longitudinal registry that will involve approximately 35 sites, I believe, and enroll 800 patients. Half of those patient will be on one of these new treatments that Dr. Levy talked with you about, and the other half will be on a variety of treatments. This will allow some degree of comparison within the limits of non-controlled data. But as you’ve heard, there’s lot of advantages of collecting real-world data. The clinical trials assessed only a single clinical event, the time to the first attack. Of course, patients enrolled in this study we’ll get their experience over a much longer period of time, and that will provide a lot of useful information.
Brian Weinshenker, MD (07:00):
So there’ll be both regular visits, and if patients experience relapse, the patients will be seen. We will be piloting the use of a tool that has been developed with the Guthy-Jackson Foundation called Relapse Navigator to enhance the confidence that a clinical event truly is a relapse. So the use of that Relapse Navigator will be integrated to capture information about relapses, but the registry will collect information on quality of life and a broad number of outcome measures that are relevant to patients with NMO, not just relapses.
Michael Levy, MD, PhD (07:48):
I would add from the academic point of view, these types of data sets are really important for researchers to be able to answer questions. So this data set will be available for outside researchers who have interests in the NMO disease course and can partner with the organization to get some of that data and to analyze it, and we’ll all publish together on it. I think that that’s a really important factor for not only for each site to consider their participation, but also for patients to feel like they’re contributing to the science.
Leslie Harrold, MD, MPH (08:30):
Yeah, absolutely. So I’m the Chief Scientific Officer, and I direct the epi and biostat group. We have over 55 Master’s and PhD epidemiologists and biostatisticians. We work with investigators to help formulate questions, to then analyze the data and then present it in the public domain. Our purpose is really to improve patient care and improve our understanding of the disease. We very much look forward to working with partners to get that knowledge out there.
Michael Levy, MD, PhD (09:07):
I think as sites come online, there’ll be more available, closer options. I think at the moment, there are about eight to ten sites that are currently enrolling around the United States. Right now you do have to come in person, and there’s a survey process and data collection process that’s involved. Then we’re hoping that the patients come back every six months to the same site. So ideally it would be someplace close and accessible to the patient and maybe even at their doctor’s office.
Brian Weinshenker, MD (09:44):
Yeah, I think that real-world data is really essential, as Leslie has pointed out. Clinical trials are clearly the standard but miss important points about patients’ comorbidity and their real-world experience. So gaining real-world experience is helpful, in part for comparison between different agents and just understanding the interaction between diverse patient factors and treatment. So I think these type of data through registries is going to be very impactful for management of patients with NMOSD.
Brian Weinshenker receives royalties from RSR Ltd, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for neuromyelitis optica spectrum disorders, served on adjudication committee for clinical trials conducted by MedImmune/VielaBio, Alexion, and UCB Biosciences and consulted for Chugai/Roche/Genentech, Horizon Therapeutics and Mitsubishi-Tanabe regarding neuromyelitis optica spectrum disorders. He has received honoraria for speaking at internal meetings of Genentech, Novartis, and external meetings for Roche.
Michael Levy received consulting fees from Horizon, Alexion and Genentech/Roche, the manufacturers of the drugs discussed in this video.
Leslie Harrold is an employee and shareholder of CorEvitas, LLC. Consultant to AbbVie, Bristol Myers-Squibb, Roche, Speakers Bureau Bristol Myers-Squibb.