The director of the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology discussed unmet needs of care for patients with neuromyelitis optica spectrum disorder.
Sean Pittock, MD
This is a 2-part interview. For part 1, click here.
Once not even considered an independent disease, the understanding of neuromyelitis optica spectrum disorder (NMOSD) and how to treat patients with the disease, has improved greatly over the past decade. NMOSD causes acute optic neuritis, sometimes bilateral, plus demyelination of the cervical or thoracic spinal cord. The autoimmune disease is characterized by—in most cases—the presence of antibodies for aquaporin-4 (AQP4), a protein that is present on astrocytes in the brain and particularly the spinal cord and optic nerves, and possibly other therapeutic targets.
The recent discovery of AQP4 led to the breakthrough of the first treatments for this disease. Beginning in 2019 with Alexion Pharmaceuticals’ eculizumab (Soliris), the FDA then greenlit inebilizumab (Uplizna; Viela Bio) in June 2020 and satralizumab (Enspryng; Genentech) in August 2020. Corticosteroids and immunomodulatory or immunosuppressive treatments have also shown benefit within this patient population. Sean Pittock, MD, has first-hand experience with understanding the clinical pipeline of the disease, serving as an investigator for multiple notable trials such as PREVENT (NCT01892345) and N-MOMENTUM (NCT02200770).
Pittock, director of the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, believes that treatment optimization and enriching the pipeline with more easily administered therapies may be the next steps to improving overall management of the disease. He headlined the latest edition of NeuroVoices by providing context on the recent advances within the field, areas that still need to be addressed, and mechanisms that have high potential to target.
Sean Pittock, MD: 2019 was what many considered the year for NMO. The reason for that was the completion of 3 randomized controlled trials that included 3 different therapies. There was the PREVENT trial, which was a study of eculizumab, a drug that blocks complement. It showed dramatic results, with a significant reduction in the likelihood of having a clinical relapse. We saw N-MOMEMTUM, which was a trial of inebilizumab, which is a drug that inhibitors or kills B-cells that are expressing CD19. Lastly was the SAkuraSky and SAkuraStar studies, which investigated satralizumab, which is an IL-6 (interleukin-6) receptor inhibitor.
All these drugs showed a dramatic ability to reduce the likelihood of a clinical relapse of NMOSD when compared to placebo. This led to the FDA approval for these drugs in North America, which is just an amazing feat for the neurological research community. We started off with a rare orphan disease, which was NMO, and we had criteria for the clinical diagnosis of that disease back in the late 1990s. The discovery of the biomarker for NMOSD, the water channel antibody, revolutionized how we thought about the disease. The Aquaporin-4 antibody is the first serum biomarker that’s specific for any form of inflammatory demyelinating disease. The discovery of that led to a better understanding of the mechanisms behind the disease. Over the last 5 years, that led to a variety of drugs that potentially we thought could benefit patients. It’s been a great adventure overall. For patients with the disease, it’s a very good time for them with a lot of hope and knowing that there are drugs that can help prevent disability.
Now that we have 3 drugs, there are issues that are related to those specific drugs, one being cost. These are very costly medications. Though they may be available to patients in the US covered by insurance, there are many patients around the world who don’t have access or potentially won’t have access to these medications. There are other medications that have been used for NMO. Rituximab (Rituxan) was the mainstay treatment for many experts that cared for patients with NMO. There was a small, randomized trial called the RIN-1 study that showed benefit. There have been other retrospective studies that have shown benefit for rituximab as well. Rituxumab is also an option, a much cheaper option, but it hasn’t been FDA-approved.
There are many other drugs that have not been studied in the context of a randomized controlled trial that we think could also benefit patients. Many of these are tablets or immunosuppressant medications. We’re tending to move towards the FDA-approved drugs because these have been proven, whereas others are just retrospective analyses of treatment approaches that have been used in different institutions.
There is some potential out there. There are many newer drugs that are coming out that still have an impact on the pathways that are important in the development of disability in NMOSD. For example, Alexion has developed a longer-acting anti-compliment drug which is given every 8 weeks rather than 2. It would have huge implications for patients because getting an infusion every 2 weeks is problematic for most cases, especially those who live in rural areas or who don’t have access to home infusion centers nearby. There are other potential mechanisms that could be looked at in NMO. For example, the potential for stem cell transplant therapies. The possibility of using a therapy that has high cost initially, but that wouldn’t require any further immunotherapy. That also would be attractive. Whether or not that’s something the NMO community would have an appetite for, and whether that would be something that could be funded, is another big question. That’s not going to be funded by an industry for pharma. But there is some preliminary data that might potentially result in a longer term benefit for patients while removing the potential that those patients would need long-life or lifelong therapy.
Absolutely. Inebilizumab is given every 6 months, so that’s very attractive to patients. Whether you can beat the frequency and mode of administration of that drug with other drugs is not clear. But yes, could we develop tablet medications or subcutaneous medications that could result in a robust inhibition of complement. Remember that with eculizumab, there is a risk, although low, of meningococcal infections or meningococcal meningitis. It would be beneficial to patients if there were drugs that could potentially impact the complement system, but in a way that wouldn’t have an increased risk of those types of infections.
Transcript edited for clarity. For more editions of NeuroVoices, click here.