Satralizumab-mwge for Neuromyelitis Optica Spectrum Disorder in Adults

Overview

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by inflammatory lesions that primarily affect the optic nerve and spinal cord. NMOSD attacks can lead to permanent vision impairment and paralysis, along with pain, fatigue, sensory loss, and bladder dysfunction.¹ Recently, eculizumab and inebilizumab were approved by the FDA for the treatment of NMOSD in adults in 2019 and 2020, respectively. Prior to their approval, no medications were approved to treat this disease. On August 14, 2020, the FDA approved satralizumab-mwge (Enspryng; Genentech) for the treatment of NMOSD in adult patients who are anti–aquaporin-4 (AQP4) antibody positive. The exact mechanism of satralizumab in NMOSD is unknown, but it involves the inhibition of interleukin-6 (IL-6) mediated signaling, which is thought to play a key role in NMOSD pathogenesis.²

Efficacy

Two multicenter, double-blind, placebo-controlled trials were conducted in two 96-week clinical studies to determine the safety and efficacy of satralizumab in NMOSD. The SAkuraStar trial (NCT02073279) included 95 patients, of which 64 were anti-AQP4 positive. Patients were randomized 2:1 to receive either satralizumab (N = 41) or placebo (N= 23) subcutaneously at weeks 0, 2, 4, and once every 4 weeks after. Study results showed that treatment with satralizumab reduced the number of NMOSD relapses by 74% in patients who were anti-AQP4 positive compared with placebo. In the satralizumab group, 82.9% and 76.5% of patients were relapse free at 48 and 96 weeks, respectively.³

The SAkuraSky trial (NCT02028884) randomized anti-AQP4 positive patients to receive satralizumab plus immunosuppressive therapy (IST) with corticosteroids, azathioprine, or mycophenolate mofetil (N = 26) or placebo plus IST (N = 26) at weeks 0, 2, 4, and once every 4 weeks after. Satralizumab reduced the number of relapses by 78% compared with placebo. 91.1% of patients in the satralizumab arm were relapse free at both 48 and 96 weeks.4There was no evidence of a benefit in anti–AQP4 negative patients in either trial.^3,4

Safety

The prescribing information for satralizumab includes a warning for increased risk of infections, specifically potential reactivation of hepatitis B and tuberculosis. Therefore, satralizumab is contraindicated in patients with an active hepatitis B infection, or active or untreated latent tuberculosis. Satralizumab also has been shown to increase liver enzymes, decrease neutrophil counts, and increase the risk for hypersensitivity reactions. Health care providers should screen patients for hepatitis B virus, tuberculosis, and liver transaminases prior to the first dose and assess for active infection prior to every use.² The most common adverse effects seen in the SAkuraStar and SAkuraSky trials include rash, arthralgia, nasopharyngitis, headache, upper respiratory tract infections, gastritis, joint pain, extremity pain, fatigue, and nausea.^3,4 Live attenuated or live vaccines are not recommended during treatment and should be administered at least 4 weeks prior to initiating therapy.²

Dosing and Administration

Satralizumab is intended for self-administration and dispensed as a 1 mL single-dose prefilled syringe. Initial dosing is 120 mg given subcutaneously every other week for a total of 3 injections. This is followed by maintenance doses of 120 mg once every 4 weeks. Prior to use, patients or caregivers should remove the prefilled syringe from the refrigerator and allow the syringe to sit at room temperature outside of the carton for 30 minutes. The solution should be clear and colorless to slightly yellow. Patients should inject the full amount of the syringe into the abdomen or thigh, and they should rotate injection sites with each administration.²

If a dose of satralizumab is missed for any reason other than increases in liver enzymes and it has been less than 8 weeks since the last dose, administer a dose as soon as possible and continue the dosing schedule from there. If it has been 8 to 12 weeks since the last dose, administer 120 mg at 0 and 2 weeks, followed by 120 mg every 4 weeks. If it has been 12 weeks or longer, administer 120 mg at 0, 2, and 4 weeks, followed by 120 mg every 4 weeks.²

References

1. FDA approves Genentech’s Enspryng for neuromyelitis optica spectrum disorder. News release. Genentech; August 14, 2020. Accessed October 6, 2020. https://www.gene.com/media/press-releases/14873/2020-08-14/fda-approves-genentechs-enspryng-for-neu

2. Enspryng. Package insert. Genentech Inc; 2020. Accessed August 17, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761149s000lbl.pdf

3. Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomized, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402-412. doi:10.1016/S1474-4422(20)30078-8

4. Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114-2124. doi:10.1056/NEJMoa1901747