Enspryng (satralizumab-mwge) for NMOSD

What is Enspryng?

Enspryng (satralizumab-mwge) is an antibody therapy approved for adults with neuromyelitis optica spectrum disorder (NMOSD) who test positive for antibodies against the aquaporin-4 (AQP4) protein.

Enspryng is sold by Genentech, a member of the Roche Group. It is administered by subcutaneous, or under-the-skin, injection and has been shown in clinical trials to reduce relapse risk.

NMOSD is an autoimmune disease in which the immune system mistakenly attacks healthy parts of the nervous system. These attacks, called relapses, can cause symptoms to suddenly worsen and may lead to permanent nerve damage over time.

In most people with NMOSD, the immune system produces antibodies that target AQP4, a water channel protein found on neuron-supporting cells called astrocytes.

Enspryng is an antibody-based therapy that acts as an interleukin-6 (IL-6) receptor inhibitor. IL-6 is an immune signaling protein that plays an important role in the inflammation that drives NMOSD, including by stimulating the production of anti-AQP4 antibodies. By blocking IL-6 receptors, Enspryng is expected to reduce disease-driving processes and lower the risk of relapses.

Therapy snapshot

Who can take Enspryng?

Enspryng is approved in the U.S. to treat adults with NMOSD who test positive for anti-AQP4 antibodies.

According to its prescribing information, the medication is contraindicated, meaning it should not be used in people with:

• a known hypersensitivity — an allergic or other harmful immune reaction — to satralizumab or any other ingredient in Enspryng
• an active hepatitis B infection
• active or untreated latent tuberculosis

Enspryng is also approved in several other regions worldwide, although the exact indications may vary. For example, in the European Union, it is approved for people age 12 and older and may be used alone or with immunosuppressive therapy.

How is Enspryng administered?

Enspryng comes in single-dose prefilled syringes or autoinjectors and is administered by subcutaneous, or under-the-skin, injection. Patients or caregivers may give the injections after appropriate training.

The recommended dosage is 120 mg. Treatment begins with three loading doses given two weeks apart, followed by one injection every four weeks.

The medication is injected into the abdomen or thigh, and the injection site should be rotated each time. It should not be injected into skin that is tender, bruised, scarred, or otherwise damaged.

Before starting treatment, patients should be screened for hepatitis B and tuberculosis, have their liver function checked, and receive any recommended vaccines.

Patients who miss a dose should contact their healthcare team for instructions. Depending on how much time has passed, they may need one or more additional loading doses before returning to the four-week maintenance schedule.

Enspryng in clinical trials

Enspryng’s approval was mainly supported by data from two international Phase 3 clinical trials that evaluated its ability to reduce relapses in people with NMOSD. Both studies included people who tested positive or negative for anti-AQP4 antibodies.

• The SAkuraStar trial (NCT02073279) evaluated Enspryng as a standalone therapy in 95 adults with NMOSD over about two years. Among those with anti-AQP4 antibodies, Enspryng significantly reduced the risk of relapses by 74% compared with a placebo. In this group, the proportion of people without relapses was also higher with Enspryng (77% vs. 41%). However, no significant differences were observed in people who tested negative for these antibodies.
• The SAkuraSky study (NCT02028884) evaluated Enspryng in combination with stable immunosuppressive therapy in 83 people with NMOSD. Again, the findings indicated that the risk of relapse was significantly lower with Enspryng in people with anti-AQP4 antibodies, whereas no significant differences were observed in people who tested negative for these antibodies. In the 76 adults included in the U.S. prescribing information’s efficacy analysis, Enspryng reduced relapse risk by 78% among those with anti-AQP4 antibodies. After about two years, 91% of Enspryng-treated anti-AQP4-positive adults remained relapse-free versus 57% of placebo-treated adults.

Participants who completed the main SAkuraStar and SAkuraSky trials and their open-label extensions were enrolled in an open-label Phase 3b study called SAkuraMoon (NCT04660539). The goal was to evaluate Enspryng’s long-term safety and efficacy.

Results showed that, with follow-up extending to nearly nine years, adverse-event rates were lower than during the double-blind periods, while infection rates did not increase over time. At 8.8 years, an estimated 67% of patients with anti-AQP4 antibodies remained free of relapses.

Potential side effects of Enspryng

The most commonly reported side effects include:

• common cold symptoms
• headache
• upper respiratory tract infections
• inflammation of the stomach lining, or gastritis
• rash
• joint pain
• pain in the arms or legs
• fatigue
• nausea

Enspryng’s prescribing information also includes warnings about potentially serious side effects, including:

• infections, including serious and potentially fatal ones
• elevated liver enzyme levels, which may be a sign of liver injury
• low levels of immune cells called neutrophils, which help the body fight infections
• hypersensitivity reactions, which may include allergic reactions