Enspryng (satralizumab-mwge) for neuromyelitis optica
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What is Enspryng for neuromyelitis optica?
Enspryng (satralizumab-mwge) is an injection therapy approved for adults with neuromyelitis optica spectrum disorder (NMOSD) who are positive for antibodies against the aquaporin-4 (AQP4) protein. It works to reduce the risk of relapses for people with the autoimmune disease by modulating the body’s immune response.Â
The therapy was developed by Chugai Pharmaceutical, a member of the Roche group.
Therapy snapshot
| Brand Name: | Enspryng |
| Chemical Name: | Satralizumab-mwge |
| Usage: | Used to treat neuromyelitis optica spectrum disorder; can reduce relapse risk |
| Administration: | Under-the-skin (subcutaneous) injection |
How does Enspryng work?
NMOSD is a chronic autoimmune condition caused by the body’s immune system abnormally launching an inflammatory attack that damages healthy components of the nervous system, particularly the spinal cord and optic nerve. The optic nerve transmits signals between the eye and the brain.
In most people with NMOSD, this autoimmune attack is driven in part by self-reactive antibodies that target AQP4, a water channel protein present at the surface of neuron-supporting cells called astrocytes.
When the immune system launches an inflammatory attack, the activity of the various types of immune cells is coordinated by signaling molecules called cytokines. These bind to specialized receptor proteins at the surface of immune cells to direct their activity.
Enspryng is an antibody-based therapy that works by blocking the receptor for interleukin-6 (IL-6), a pro-inflammatory cytokine that is thought to play a central role in the autoimmune attacks that drive NMOSD.
By blocking IL-6 signaling, Enspryng is expected to reduce disease-driving inflammation. That, in turn, lowers the risk of disease relapses, which are associated with increasing disability that can cause patients to progressively lose their vision, and may hamper their ability to perform day-to-day tasks.
Who can take Enspryng?
Enspryng was approved by the U.S. Food and Drug Administration in 2020 to treat adults with NMOSD who are positive for anti-AQP4 antibodies. That decision made Enspryng the first under-the-skin, or subcutaneous treatment available for NMOSD.
The European Commission granted approval to the therapy in 2021 for AQP4-positive NMOSD patients 12 and older in the European Union. In Switzerland, Canada, and Taiwan, the therapy also is available for this broader patient population. Meanwhile, Enspryng’s approval in Japan covers patients of all ages.
Who should not take Enspryng?
Enspryng is not recommended for anyone with:
- a known allergy to the medication or any of its ingredients
- an active hepatitis B infection
- an active or untreated latent tuberculosis infection.
Patients with an active infection also should not take the therapy until that infection is resolved.
How is Enspryng administered in NMOSD?
Enspryng is available as a prefilled single-dose syringe containing a clear and colorless to slightly yellow solution with the recommended dose of 120 mg.
The first three injections, called the loading doses, are given two weeks apart. Subsequent injections, called the maintenance doses, are then given every four weeks.
Enspryng is administered via an under-the-skin injection into the thigh or abdomen. It can be self-administered at home by patients who have been trained in how to perform injections. However, the first doses should be given under the guidance of a healthcare professional.
Prior to injection, the syringe should be removed from refrigeration and allowed to warm at room temperature for about 30 minutes. Importantly, the injection site should alternate from dose to dose, and injections should not be administered into moles, scars, or areas of damaged or red skin.
If a planned dose is missed, an injection should be given as soon as possible, without waiting for the next planned dose. Subsequent doses should then be given every four weeks — or at two weeks if the patient is still in the loading dose phase.
If patients go more than eight weeks after missing a dose, it is necessary to administer two loading doses before restarting maintenance dosing. All three loading doses should be given if a dose is missed by more than 12 weeks.
Enspryng in clinical trials
Approvals of Enspryng were mainly supported by data from two international, two-part Phase 3 clinical trials: SAkuraStar (NCT02073279), completed in January 2022, and SAkuraSky (NCT02028884), finished in December 2021.
SAkuraStar and SAkuraSky
Together, the SAkuraStar and SAkuraSky studies included 178 adolescents and adults with NMOSD who had experienced at least one relapse in the prior year. Both trials tested Enspryng against a placebo for about four years, after which participants were invited to enter their respective extension portions, wherein all received the therapy for an extended period of time.
In SAkuraStar, which included 95 adults with NMOSD, Enspryng was given at a dose of 120 mg as a single therapy. In SAkuraSky, 83 patients, 12 years and older, received the therapy or a placebo in addition to standard immunosuppressive medications — namely azathioprine, mycophenolate mofetil, or oral corticosteroids.
Participants in both trials were primarily female, were positive for anti-AQP4 antibodies, and had substantial disability, but were not wheelchair-bound.
Results from both trials showed Enspryng was safe. It also significantly outperformed a placebo in reducing the risk of relapse when used alone or in combination with usual immunosuppressive therapies. Specifically, Enspryng treatment lowered the risk of relapse by 55% in SAkuraStar and by 62% in SAkuraSky.
In both studies, the effect of Enspryng on relapse risk was significant among patients positive for anti-AQP4 antibodies, with the therapy lowering the relapse risk by 74% relative to a placebo in SAkuraStar and by 79% in SAkuraSky. However, among patients negative for these self-reactive antibodies, there was no evidence of Enspryng’s superiority over a placebo.
Compared with patients assigned to a placebo, a greater proportion of Enspryng-treated patients remained free from relapses at nearly one year — 76% versus 62% in SAkuraStar and 89% versus 66% in SAkuraSky. Similar result were seen at about two years (72% vs. 51% in SAkuraStar; 78% vs. 59% in SAkuraSky).
Data from 111 patients who entered each trial’s extension portion demonstrated Enspryng’s sustained efficacy, with a high proportion of patients with anti-AQP4 antibodies remaining free from relapses (71%-73%) and severe relapses (90%-91%) after more than 3.5 years of treatment.
Most patients in both trials — 86%-90% — also did not experience sustained disability worsening, or an increase in scores on the Expanded Disability Status Scale (EDSS) that was confirmed at least six months later.
SakuraMoon
Patients who completed both the placebo-controlled and extension portions of either trial were rolled into an open-label extension study called SAkuraMoon (NCT04660539). Designed to evaluate Enspryng’s long-term safety and efficacy, its participants are being treated with the therapy for up to three more years. Participants can receive Enspryng alone or with standard immunosuppressive treatments.
An interim analysis involving 106 AQP4-positive NMOSD patients — the results of which were shared in May 2023 — showed nearly 3 in 4 were relapse-free after more than 4.5 years on Enspryng. Further, more than 90% did not have a severe relapse. The vast majority of patients (85%) were free from sustained disability worsening.
Ongoing trials
Roche now will test Enspryng in children with NMOSD, in a Phase 3 trial called SAkuraSun (NCT05199688). This trial will involve up to eight children, ages 2 to 11, who are positive for anti-AQP4 antibodies. All participants will be treated with Enspryng, at doses based on body weight, for at least 48 weeks, or roughly one year.
The study’s main goal is to evaluate Enspryng’s pharmacological and safety profile in these young patients. The therapy’s effect on relapses, disability progression, pain, and quality of life also will be assessed. Top-line data is expected in late 2024 and the trial is set to conclude in 2027.
A Phase 4 trial is assessing Enspryng’s ability to prevent relapses and disability progression in NMOSD patients who either have never been treated before or who failed to respond to treatment with rituximab. Dubbed SAkuraBonsai (NCT05269667), it is testing the therapy in up to 100 adults with AQP4-related NMOSD.
All participants, who must be within five years of the first onset of NMOSD symptoms, will be treated with Enspryng for nearly two years. Top-line data is expected in 2026.Â
Common side effects of Enspryng
The most common side effects of Enspryng, affecting at least 15% of patients, include:
- the common cold
- headache
- upper respiratory tract infections
- stomach inflammation, or gastritis
- rash
- pain in the joints or extremities
- fatigue
- nausea.
Infections and vaccines
Because it works by decreasing immune activity, Enspryng can increase a person’s risk of infections. The therapy also reduces the body’s ability to fight currently active or latent infections.
Prior to administering the first dose of Enspryng, patients should be tested for active hepatitis B infection and active or latent tuberculosis; their presence prevents treatment initiation. Also, the therapy should not be administered to anyone with an active infection. If an individual has an infection, including any localized infections, when a dose is planned, the dose should be delayed until it has resolved.
Vaccines containing a live virus should not be given during Enspryng treatment. Patients who have recently received vaccines containing a live, weakened virus must wait at least four weeks before starting Enspryng. If possible, individuals receiving other vaccines without a live virus should only initiate therapy after at least two weeks.
Liver damage
Enspryng may cause liver damage in some patients. Markers of liver health should be monitored before initiating treatment, and every four weeks during the first three months on the medication. Monitoring should then be done every three months for one year, and as clinically indicated thereafter.
Physicians should proceed with caution if patients develop higher than normal levels of certain liver enzymes, suggesting liver damage. If patients show several signs of liver damage while taking Enspryng, it may be necessary to pause treatment or discontinue it altogether.
Immune deficiencies
Patients on Enspryng may experience a decrease in levels of neutrophils, a type of immune cell that’s important for fighting infections. Neutrophil levels should be checked a month or two after starting on Enspryng, and at regular intervals thereafter. If patients show neutrophil counts that are dramatically lower than normal, treatment should be interrupted until levels rise.
Allergic reactions
Allergic reactions, including fatal reactions, have been reported in patients given IL-6-blocking therapies like Enspryng. The therapy should never be given to anyone with a known allergy to its ingredients, and if an allergic reaction occurs, treatment should be stopped immediately.
Use in pregnancy and breastfeeding
The use of Enspryng in people who are pregnant or breastfeeding has not been rigorously studied. In studies done in monkeys, administration of Enspryng during pregnancy did not cause any notable problems with fetal development, though babies were born with lower than normal immune function.
Animal studies also have shown that Enspryng is excreted in breast milk. However, the therapy’s presence in human breast milk and its potential effects on a breastfed infant, or on milk production in nursing patients, remain largely unclear.
Patients and their care teams should work together to evaluate the potential risks and benefits of Enspryng use by individuals who are pregnant or breastfeeding. A registry is collecting data on patients who are exposed to Enspryng during pregnancy; patients or healthcare providers can contact the registry at 1-833-277-9338.
Neuromyelitis News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Enspryng
The potential interaction between Enspryng and alcohol has not been thoroughly investigated, and clinical trials testing the therapy excluded patients with a recent history of alcohol abuse. It’s known that Enspryng can cause liver damage, and drinking alcohol, especially in large quantities, also can damage the liver; therefore, it’s recommended that patients talk to their healthcare team about whether it is safe for them to drink alcohol while taking Enspryng.
Enspryng has not been rigorously studied in pregnant people. In studies done in pregnant monkeys, the therapy did not cause developmental problems, but animals were born with impaired immune function. Patients should talk with their doctor about any plans for being pregnant while on the therapy. A registry is collecting data on patients exposed to Enspryng during pregnancy; it can be contacted at 1-833-277-9338.
Hair loss has not been reported as a side effect of Enspryng in clinical trials. However, several patients experienced a meaningful increase in weight while on treatment. It is recommended that patients speak with their healthcare team if they experience any unanticipated side effects during Enspryng treatment.
In the trials that supported the therapy’s approval, a pronounced difference in terms of the proportion of relapse-free patients between the Enspryng and placebo groups was evident after about one year. But because each person can respond differently to a medication, patients are advised to talk with their healthcare team on how the therapy may help in their particular case.
The U.S. Food and Drug Administration (FDA) approved Enspryng in August 2020 as a treatment for adults with neuromyelitis optica spectrum disorder (NMOSD) who are positive for antibodies against aquaporin-4, the most common type of disease-driving antibody. The medication became the first subcutaneous, or under-the-skin, treatment approved for NMOSD.
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