#ACTRIMS2021 – Expert Lectures About Available NMOSD Treatments
An improved understanding of the biological processes that drive neuromyelitis optica spectrum disorder (NMOSD) has led to treatment advancements in recent years.
In a presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021, Sean Pittock, MD, director of the Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology, reviewed the current understanding of the biology of NMOSD. He discussed how this understanding has led to the development and approval of new therapies. The presentation was titled, “NMO and anti-MOG: Updates on Diagnosis and Treatment.”
NMOSD is caused by the body’s immune system erroneously launching an attack against healthy cells in the central nervous system (the brain and spinal cord).
Most people with NMOSD have abnormally high levels of an antibody called anti-aquaporin-4 (AQP4-IgG). This antibody directs an immune attack against astrocytes (a type of cell in the central nervous system).
Recently, three different medications with different mechanisms of action have been approved to treat NMOSD in the U.S. and elsewhere.
Soliris (eculizumab), developed by Alexion Pharmaceuticals, works by blocking the activity of the complement system, which is a group of immunological proteins in the blood. Uplizna (inebilizumab-cdon), by Viela Bio, works by targeting B-cells (the immune cells that make AQP4-IgG and other antibodies). Enspryng (satralizumab-mwge), by Chugai Pharmaceutical (a subsidiary of Roche), works by blocking an inflammatory signaling molecule called interleukin-6 (IL-6).
In clinical trials, these medications were shown to reduce the risk of relapses — by 74% to 94%, depending on the specific study — with no major safety concerns identified. Pittock stressed that, in NMOSD, disability tends to accumulate along with relapses.
“Therefore, prevention of attacks [relapses] potentially will reduce or prevent disability,” he said.
The specific clinical trials include PREVENT (NCT01892345), which tested Soliris; N-MOmentum (NCT02200770), which tested Uplizna; and SAkuraStar (NCT02073279) and SAkuraSky (NCT02028884), both of which evaluated Enspryng.
Another clinical trial, called RIN-1, tested rituximab, a B-cell targeting medication that is not currently approved to treat NMOSD. In the U.S. and elsewhere, rituximab is approved to treat certain cancers and autoimmune diseases; it is marketed under the brand name Rituxan, among others.
Results from RIN-1 were generally positive — no relapses occurred in the 19 participants given rituximab — but the trial was too small to make statistically meaningful conclusions.
Pittock highlighted some noteworthy differences in the designs of the various trials. For instance, in PREVENT and SAkuraSky, participants were allowed to be on other standard-care therapies, whereas in SAkuraStar and N-MOmentum, no other treatments were allowed.
He also noted factors that need to be taken into consideration when patients and their healthcare teams are making decisions about which treatment(s) to use.
For example, he highlighted convenience as a major factor. Soliris is administered by infusion every two months, while Uplizna and rituximab are given by infusion every six months. Enspryng is administered by subcutaneous (under-the-skin) injection once per month.
“Obviously, this will have an importance when picking a drug for patients that have frequent travel for work or have busy schedules,” Pittock said.
He also highlighted cost as a “significant issue.”
According to Pittock, Soliris costs about $710,000 per year. Uplizna costs about $393,000 in the first year, then $262,000 every year thereafter. Enspryng costs $219,000 in the first year, then carries a yearly price tag of $190,000.
These were “compared with $18,000 per year, and dropping, for rituximab,” Pittock said.
Pittock also noted areas where more research still needs to be done. For example, he noted a need to better understand the effectiveness of different medications in combinations, as opposed to individual therapies.
Another open question is whether people who previously were stable on immune-suppressing treatments like steroids should be switched to one of the now-approved therapies, or continue on the regime that has worked for them so far, he said.
MOG-associated disorder (MOGAD) is a condition similar to NMOSD. Both are characterized by brain inflammation and damage to the optic nerves (the nerves connecting the eyes to the brain). However, emerging research indicates the two conditions are distinct clinical entities.
Whereas NMOSD is characterized primarily by AQP4-IgG, MOGAD is characterized by antibodies targeting MOG (MOG-IgG), which is a protein found on oligodendrocytes, another kind of nervous system cell.
Pittock highlighted differences between NMOSD and MOGAD. For example, whereas NMOSD relapses often are followed by increasing disability, MOGAD relapses are associated with less disability accumulation.
The current standard for treating MOGAD includes immune-suppressing steroids. So far, no clinical trials have been conducted in MOGAD.
“We’re hopeful that in the future we will have randomized control trials that hopefully will be as positive as we have had for [NMOSD],” Pittock said.