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- Title
(RTH05) Characterization of the Pharmacokinetics and Pharmacodynamics of Satralizumab, a Recycling Antibody, to Support Once-Every-4-Weeks Dosing in Patients with Neuromyelitis Optica Spectrum Disorder.
- Authors
Lennon-Chrimes, Sian; Silber Baumann, Hanna; Klingelschmitt, Gaelle; Xiujing Kou; Sanwald Ducray, Patricia; Anania, Veronica G.; Hajime Ito; von Buedingen, H.-Christian
- Abstract
Background: Interleukin-6 (IL-6) has been implicated in the immunopathology of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab is a subcutaneously administered monoclonal antibody that binds to and blocks the IL-6 receptor (IL-6R). Satralizumab was engineered to be recycled back into circulation via the neonatal Fc receptor (FcRn), increasing its serum half-life and effecting prolonged inhibition of IL-6R signaling. Objectives: To define an effective, convenient, long-term dosing regimen for satralizumab in patients with NMOSD. Methods: The pharmacologic characteristics (pharmacokinetics [PK] and pharmacodynamics) of satralizumab were assessed in 72 Japanese healthy volunteers (HVs; single dose, range 30-240 mg), 33 patients with rheumatoid arthritis (RA) (multiple doses, range 30-120 mg), and 104 patients with NMOSD from two phase 3 studies in NMOSD (SAkuraSky [trial registration: NCT02028884] and SAkuraStar [NCT02073279]; 120 mg loading, once every 4 weeks). A popPK model, based on HV and NMOSD data, was used to derive predictions for individual PK parameters. Results: Satralizumab provided significant inhibition of IL-6R signaling for 4 weeks; target engagement resulted in sustained increases in soluble IL-6R levels in HVs and patients with RA and NMOSD. In the NMOSD population, the PK of satralizumab was shown to be nonlinear, with an effective half-life of approximately 30 days at a dose of 120 mg; the median predicted IL-6R occupancy was maintained at >95% throughout the 4-week dose interval. Meaningful and comparable efficacy vs placebo was demonstrated in patients with NMOSD in both phase 3 studies: hazard ratio (95% CI) for reduction in protocol-defined relapse risk was 0.38 (0.16-0.88), P = .0184 in SAkuraSky; and 0.45 (0.23-0.89), P = .0184 in SAkuraStar. Satralizumab showed a favorable safety profile in patients with NMOSD when administered as monotherapy or in combination with baseline immunosuppressants. Conclusions: The recommended 120-mg loading and every-4-weeks maintenance regimen of satralizumab represents an effective, safe, and convenient treatment in NMOSD.
- Subjects
CONFERENCES &; conventions; IMMUNOGLOBULINS; NEUROMYELITIS optica
- Publication
International Journal of MS Care, 2020, Vol 22, Issue S2, p78
- ISSN
1537-2073
- Publication type
Article