Breakthroughs in NMOSD: Better Understanding the Science and Treatment


Sponsored by Genentech

For decades, limited understanding and a lack of available treatment options made neuromyelitis optica spectrum disorder (NMOSD) an especially difficult diagnosis for neurologists to make and deliver. A rare and lifelong autoimmune disease that impacts the optic nerve(s) and spinal cord,1 NMOSD affects up to 15,000 people in the U.S.,2 and can cause lasting damage to the nervous system, including blindness, muscle weakness and even paralysis.1,3 Due to its overlapping characteristics with multiple sclerosis (MS), NMOSD is often misdiagnosed and can worsen if treated improperly with MS medication or if left untreated.4

The importance of proper diagnosis and treatment for NMOSD cannot be underestimated. Without treatment, in just five years from diagnosis, up to half of people with NMOSD will likely require a wheelchair, and more than 60 percent may become functionally blind.1,3 Until recently, there were no medicines specifically evaluated and approved to treat NMOSD, leaving healthcare professionals with limited options for treatment. Given the progressive nature of this debilitating condition, the medical community was in need of targeted treatments.

Fortunately, the understanding of NMOSD has improved substantially, thanks to continued investment in neuroscience research and development, and collaboration between biotechnology companies, healthcare providers and patient advocacy organizations. These advancements have paved the way for Genentech, a member of the Roche Group, to better understand NMOSD and advance treatment.

Meaningful Advancements in Understanding the Science of NMOSD

Although it’s not clear what causes NMOSD, there is strong scientific evidence that interleukin-6 (IL-6), a protein made by immune cells, may play a key role in the inflammation associated with the condition. IL-6 helps regulate the body’s immune response to inflammation, including the production of aquaporin-4 (AQP4) antibodies, which target and damage cells found in the optic nerves, brain and spinal cord. In response, these cells produce even more IL-6. In fact, IL-6 has been found in excess in the blood and brain of people diagnosed with NMOSD. Increased IL-6 can lead to more inflammation, which can lead to relapses, one of the clinical hallmarks of the condition. These unpredictable, severe relapses may cause cumulative, irreversible, neurological damage and disability for those living with NMOSD.1,3

Ashish Pradhan, M.D., Executive Director of Neuroimmunology at Genentech, explained that this improved understanding of the connection between IL-6 and NMOSD inspired researchers at Chugai, another member of the Roche Group, to explore what happened when IL-6 receptor activity was blocked. “They hypothesized that by blocking IL-6 signaling pathways, it could reduce the inflammation commonly seen in people with NMOSD. A novel recycling antibody technology was used so that after binding to the IL-6 receptor, the treatment being designed could be released back into circulation, allowing it to bind to other IL-6 receptors. This continued investment in research and development paved the way for our team at Genentech to better understand the condition and help deliver a new, innovative treatment.”

Changing the NMOSD Treatment Landscape

It has been a little over one year since EnspryngTM (satralizumab-mwge) was approved by the U.S. Food and Drug Administration in August 2020 as the first and only subcutaneous treatment option for adults with AQP4 antibody-positive NMOSD, which is detectable in approximately 80 percent of those living with the NMOSD.6 It is also the only approved NMOSD therapy designed to target and inhibit the IL-6 receptor.

Enspryng was studied in one of the largest pivotal clinical trial programs undertaken for this rare neurological disease. The two studies -- SAkuraSky and SAkuraStar -- found that Enspryng significantly reduced the risk of relapse in AQP4 positive patients at 96 weeks compared to treatment with a placebo by 74% and 78% respectively [HR = 0.26, 0.22; CI = (0.11, 0.63), (0.06, 0.82); p = 0.0014, 0.0143].7,8 Enspryng is contraindicated in patients with a known hypersensitivity to satralizumab or any of the inactive ingredients, an active hepatitis B infection, or active or untreated latent tuberculosis. The warnings and precautions for Enspryng are infections, including hepatitis B virus reactivation and tuberculosis, elevated liver enzymes, decreased neutrophil counts, and hypersensitivity reactions. Appropriate precautions should be taken by the healthcare provider when considering vaccinations.

“For decades, we relied on unproven or off-label therapies in a sort of ‘blunt force’ approach to treat NMOSD,” said Geoffrey Eubank, M.D., System Medical Chief, General Neurology at OhioHealth Neurological Physicians and one of the Enspryng clinical trial investigators. “Exploring the role of IL-6 in NMOSD and discovering a treatment to block those chemical messengers and reduce attacks has filled a significant gap in how NMOSD is treated and provided much-needed hope for patients and those of us who treat them.”

In addition to its IL-6 inhibition, Enspryng was designed using novel recycling antibody technology that allows for longer duration of antibody circulation and subcutaneous dosing every four weeks.9,10 Instead of needing to go to a healthcare facility for infusion therapies, Enspryng can be self-administered by a person living with NMOSD or a caregiver at home, after an initial loading dose and following training from a healthcare provider, if deemed appropriate by a physician.

Continuing to Advance the Science of NMOSD

While Genentech has made a tremendous advancement in NMOSD, its work isn’t over yet. The discovery of the role of IL-6 role in NMOSD has redefined the company’s understanding of the condition and it remains committed to advancing NMOSD clinical research, including ongoing safety and efficacy studies with Enspryng. Genentech is also conducting research to gain a deeper scientific understanding of NMOSD in diverse patient populations that could help provide better care for those living with the condition.

Dr. Pradhan added, “We are proud of the progress we have made in addressing many key challenges that have long eluded the neuroscience community, including NMOSD and other neurological conditions that limit human potential. To sustain this forward trajectory, we must continue to follow the science, push the boundaries of scientific understanding, monitor the safety and efficacy of our treatments and keep patients where they belong -- at the heart of our research. We can then look to the future of neuroscience with more confidence, knowing that we will continue to focus on areas with the highest unmet needs and provide patients with the support and care needed to live their best lives beyond their disease.”

For more information on Enspryng, please visit

Important Safety Information & Indication


ENSPRYNG is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.


ENSPRYNG is contraindicated in patients with a known hypersensitivity to satralizumab or any of the inactive ingredients, an active hepatitis B infection, or active or untreated latent tuberculosis.

Warnings and Precautions


An increased risk of infections, including serious and potentially fatal infections, has been observed in patients treated with IL-6 receptor antagonists, including ENSPRYNG. The most common infections reported in a randomized clinical trial of patients treated with ENSPRYNG who were not on other chronic immunosuppressant therapies and that occurred more often than in patients receiving placebo, were nasopharyngitis (12%) and cellulitis (10%). The most common infections in patients who were on an additional concurrent immunosuppressant, and that occurred more often than in patients receiving placebo, were nasopharyngitis (31%), upper respiratory infection (19%), and pharyngitis (12%). Delay ENSPRYNG administration in patients with an active infection, including localized infections, until the infection is resolved.

Hepatitis B Virus (HBV) Reactivation

Risk of HBV reactivation has been observed with other immunosuppressant therapies. Patients with chronic HBV infection were excluded from clinical trials. Perform HBV screening in all patients before initiation of treatment with ENSPRYNG. Do not administer ENSPRYNG to patients with active hepatitis. For patients who are chronic carriers of HBV [HBsAg+] or are negative for HBsAg and positive for HB core antibody [HBcAb+], consult liver disease experts before starting and during treatment with ENSPRYNG.


Tuberculosis has occurred in patients treated with other IL-6 receptor antagonists. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating ENSPRYNG. Consider anti-tuberculosis therapy prior to initiation of ENSPRYNG in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consult infectious disease experts regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment. Patients should be monitored for the development of signs and symptoms of tuberculosis with ENSPRYNG, even if initial tuberculosis testing is negative.


Live or live-attenuated vaccines should not be given concurrently with ENSPRYNG because clinical safety has not been established. Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of ENSPRYNG for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ENSPRYNG for non-live vaccines.

Elevated Liver Enzymes

Mild and moderate elevations of liver enzymes have been observed in patients treated with ENSPRYNG at a higher incidence than in patients receiving placebo. ALT and AST levels should be monitored every 4 weeks for the first 3 months of treatment, followed by every 3 months for one year, and thereafter, as clinically indicated.

Decreased Neutrophil Counts

Decreases in neutrophil counts were observed in patients treated with ENSPRYNG at a higher incidence than placebo. Neutrophil counts should be monitored 4 to 8 weeks after initiation of therapy, and thereafter at regular clinically determined intervals.

Hypersensitivity Reactions

Hypersensitivity reactions, including rash, urticaria, and fatal anaphylaxis, have occurred with other IL-6 receptor antagonists.

Use in Specific Populations


There are no adequate data on the developmental risk associated with the use of ENSPRYNG in pregnant women. In an animal reproduction study, no adverse effects on maternal animals or fetal development were observed in pregnant monkeys and their offspring, with administration of ENSPRYNG at doses up to 50 mg/kg/week. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.


No information is available on the presence of ENSPRYNG in human milk, the effects of ENSPRYNG on the breastfed infant, or the effects of ENSPRYNG on milk production. ENSPRYNG was excreted in the milk of lactating monkeys administered ENSPRYNG throughout pregnancy. Human IgG is excreted in human milk and the potential for absorption in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ENSPRYNG and any potential adverse effects on the breastfed infant from ENSPRYNG or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of ENSPRYNG did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. However, population pharmacokinetic analyses in patients with NMOSD did not show that age affected the pharmacokinetics of ENSPRYNG. In general, caution should be used when dosing the elderly, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Most Common Adverse Reactions

The most common adverse reactions (≥15% in either trial) were nasopharyngitis (31%), headache (27%), upper respiratory tract infection (19%), rash (17%), arthralgia (17%), extremity pain (15%), gastritis (15%), fatigue (15%), and nausea (15%).

For additional safety information, please see the full Prescribing Information and Medication Guide.

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