Satralizumab Eliminates Protocol-Defined Relapse in NMOSD, Long-Term Analysis Demonstrates
Low annualized relapse rates determined by investigator were observed and sustained over a 3.5-year period with treatment of satralizumab.
Ingo Kleiter, MD
New findings presented at the 2022 American Academy of Neurology (AAN) annual meeting, April 2-7, in Seattle, Washington, showed long-term benefits to treatment with satralizumab (Enspryng; Genentech) in patients with aquaporin-4 immunoglobulin positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD).
Approved by the FDA in 2020, satralizumab-treated patients demonstrated high rates of freedom from relapse, severe relapse, or worsening disability for at least 3.5 years in this analysis. In the SAkuraSky (NCT0202884) and SAkuraStar (NCT02073279) studies, the mean annualized protocol-defined relapse (PDR) rate determined by investigators (iPDRs) closest to the cut-off date was 0.21 (SD, 0.57) and 0.20 (0.64) for the respective studies and remained stable over the course of the observed period.
Led by Ingo Kleiter, MD, assistant professor for clinical and experimental neuroimmunology, Ruhr University Bochum, the analysis evaluated patients who completed the double-blind periods (DBPs) of the phase 3 studies and opted to enter the open-label extension (OLE). Each patient received at least 1 dose of satralizumab, with data cutoff on February 22, 2021.
In the OLE, PDR were determined by the investigators, whereas PDRs in the DBPs were adjudicated by a Clinical Endpoint Committee. A total of 111 participants, 49 from SAkuraSky and 62 from SAkuraStar, were included in the analysis. Patients in those studies were exposed to satralizumab for a mean 4.4 years (range, 0.1-7.0) and 4.0 years (0.1-6.0), respectively.
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At week 192, 71% of satralizumab-treated patients in SAkuraSky were free from iDPR and 91% were free from severe iDPR, otherwise considered at least a 2-point increase on the Expanded Disability Status Scale (EDSS). Sustained worsening of EDSS, demonstrated by increases of at least 2, 1, or 0.5 points for patients with baseline scores of 0, 1 to 5, or at least 5.5, respectfully, were found in 90% of patients. Similar results were observed in SAkuraStar, with 73% of satralizumab-treated patients free from iDPR, 90% of patients free from severe iDPR, and 86% with no sustained disease worsening.
Since its approval, there have been numerous analyses from the SAkura studies which have further demonstrated satralizumab’s safe and efficacious profile. One post-hoc analysis comprised data on adverse events (AEs), reported as events per 100 patient-years (PY). Median treatment exposure was 205 weeks (range, 4-311) in SAkuraSky and 157 weeks (range, 5-265) in SAkuraStar during the treatment period. Across this period, rates of AEs and serious AEs (SAEs) were comparable to that observed in the DBP. Rates of AEs were 389.6 per 100 PY (95% CI, 365.9-414.4) and 403.0 per 100 PY (95% CI, 379.4-427.6), respectively, in the SAkuraSky and SAkuraStar studies. SAEs were also similar between the groups, with a rate of 11.2 per 100 PY (95% CI, 7.5-16.1) in SAkuraSky and 12.2 per 100 PY (95% CI, 8.4-17.1) in SAkuraStar.2
A 2020 analysis of the 2 studies highlighted satralizumab’s impact on reduction of relapse risk, including in those with treatment-naïve NMOSD. In total, 1 patient who received placebo experienced a PDR on study day 21, and 2 of the 4 satralizumab patients experienced a relapse as well. The patient on placebo who experienced a PDR had a 1.5-point increase in EDSS score and was able to fully recover to prerelapse EDSS score. As for the 2 on satralizumab, the first patient experienced a PDR on day 214, with a 1-point increase in EDSS, and the second patient experienced a relapse (not meeting PDR criteria) on day 458, with a 0.5-point increase in EDSS score. Both patients were able to fully recover to prerelapse EDSS score. Investigators noted that interpretation of the study was limited due to the small sample size.3
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