Satralizumab Post-Marketing Study Demonstrates Consistently Lower Patterns of Infection Than US Claims Data

Benjamin M. Greenberg, MD

Using data from the pivotal SAkura studies, satralizumab (Enspryng; Genentech) post-marketing (PM) data, and NMOSD US PharmMetrics Claims data, findings revealed that infections remain a major comorbidity in patients with neuromyelitis optica spectrum disorder (NMOSD); however, the incidence of infection, serious infection, and sepsis was consistently lower in satralizumab-treated patients than in US claims data.¹

Presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, the analysis included 166 patients from the SAkura studies (clinical cut-off date [CCOD]: January 31, 2023), 2951 satralizumab-treated patients in PM data (June 1, 2020-May 31, 2023), and 2872 adults from US claims data (January 1, 2017-October 31, 2022; >99% not receiving satralizumab). Incidence rates of infection/serious infection/sepsis per 100 patient-years (IR/100 PY) were analyzed in the SAkura studies, and cumulative incidence in the PM and US claims data.

Led by Benjamin M. Greenberg, MD, a pediatric neurologist at the University of Texas Southwestern Medical Center, results showed a lower incidence of infection (91.7 [95% CI, 85.5-98.3] vs 113.1 [95% CI, 98.8-129.0]) serious infection (2.6 [95% CI, 1.7-3.9] vs 4.1 [95% CI, 1.8-8.0]) and sepsis (0.56 [95% CI, 0.2-1.3] vs 1.01 [95% CI, 0.1-3.7) at CCOD (median exposure, 5.9 years) in the SAkura studies vs the double-blind periods. These included data from SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279), the 2 studies that led to satralizumab’s approval, as well as SAkuraMoon (NCT04660539), a follow-up open-label extension.

In the PM data, which included those exposed to satralizumab for more than 3 years, showed cumulative incidence of 7.3%, 3.8%, and 0.6% for infection, serious infection, and sepsis, respectively. In US claims data (4-year follow-up), the cumulative incidence of infection, serious infection, and sepsis was 67.4%, 8.4%, and 4.4%, respectively. Overall, in the SAkura studies, most patients with serious infection had baseline Expanded Disability Status Scale scores of higher than 4, indicating greater disability.

READ MORE: Researchers Identify Distinct Differences in Acute Optic Neuropathy of MOGAD vs Nonarterior Anterior Ischemic Optic Neuropathy

Satralizumab, a humanized monoclonal antibody that targets and inhibits interleukin-6 (IL-6) receptor activity, became the third approved treatment for NMOSD in August 2020. SAkuraStar and SAkuraSky, which combined included more than 170 patients who were randomly assigned to receive satralizumab 120 mg or placebo, served as the basis for the therapy’s approval. SAkura Sky differed slightly, as patients added treatment to baseline immunosuppressive therapy.

At eh 2023 MSMilan, the 9th joint ECTRIMS-ACTRIMS Meeting, data from the open-label SAkuraMoon showed that satralizumab had a consistently low annual relapse rates among patients with aquaporin-4-IgG-seropositive NMOSD over a 5.5-year period. After 5.5 years, 72% (95% CI, 62%–80%) of satralizumab-treated patients were free from investigator-determined protocol-defined relapse (iPDR), 91% of patients (95% CI, 83%–95%) were free from severe iPDR, and 83% of patients (95% CI, 73%–90%) had no sustained EDSS worsening. The researchers noted that only 3 patients dropped out from SAkuraMoon, 2 patients switched to commercial satralizumab, and 1 patient discontinued treatment because of pregnancy.²

Previous research has suggested that IL-6 has a role in the pathogenesis of myelin oligodendrocyte glycoprotein antibody disease (MOGAD), an autoimmune disorder that presents similar to other demyelinating disorders such as NMOSD and multiple sclerosis. METEROID, an ongoing phase 3 study (NCT05271409), assesses the efficacy, safety, pharmacokinectics, and pharmacodynamics of satralizumab as a monotherapy or an add-on to baseline immunosuppressive therapy in patients with MOGAD. The trial includes a 28-day screening period, a 44-month treatment period, and a 24-month open-label extension, with all patients switching or staying on satralizumab.³

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REFERENCES
1. Greenberg BM, Fujihara K, Weinshenker B, et al. Infection in NMOSD: analyzing the patterns of infection in the SAkura studies, satralizumab post-marketing data, and NMOSD US PharMetrics Claims data. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. ABSTRACT 003283
2. Palace J, Traboulsee A, Saiz A, et al. Long-term efficacy of satralizumab in patients with AQP4-IgG+ NMOSD: Updated analysis from the open-label SAkuraMoon study. Presented at: 2023 MSMilan; October 11-12; Milan, Italy. Abstract P362.
3. Paul F, Flanagan EP, Kumpfel T, et al. METEOROID: a randomised, double-blind, placebo-controlled,multicentre phase 3 study of satralizumab in patients with MOGAD. Presented at: 38th Congressof the European Committee for Treatment and Research in Multiple Sclerosis; October 26-28, 2022; Amsterdam, Netherlands. EP1040.