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Abstract Details

Characterisation of the PK and PD of Satralizumab, a Recycling Antibody, to Support Q4W Dosing in Patients with NMOSD
Autoimmune Neurology
P14 - Poster Session 14 (8:00 AM-9:00 AM)
15-007
To define an effective, convenient, long-term dosing regimen for satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD). 
Interleukin-6 (IL-6) has been implicated in the immunopathology of 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 signalling.
The pharmacological characteristics (pharmacokinetics [PK] and pharmacodynamics [PD]) of satralizumab were assessed in 72 Japanese healthy volunteers (HVs; single dose, range 30-240 mg), 33 rheumatoid arthritis (RA) patients (multiple doses, range 30-120 mg), and 104 patients with NMOSD in two phase 3 studies (SAkuraSky [NCT02028884] and SAkuraStar [NCT02073279]; mean 25 doses of satralizumab 120 mg once every four weeks [Q4W]). A popPK model was developed using the HV and NMOSD data, and was used to derive predictions for individual PK parameters. 
Satralizumab provided significant inhibition of IL-6R signaling for 4 weeks, demonstrated by marked, sustained increases in soluble IL-6R levels in HVs, RA and NMOSD patients. In the NMOSD population, the PK of satralizumab was shown to be non-linear, with an effective half-life of approximately 30 days at a dose of 120mg; 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=0.0184 in SAkuraSky; and 0.45 (0.23-0.89), p=0.0184 in SAkuraStar). Satralizumab showed a favorable safety profile in patients with NMOSD when administered as monotherapy or in combination with baseline immunosuppressants.
The recommended 120mg loading and Q4W maintenance regimen of satralizumab represents an effective, safe and convenient treatment in NMOSD.
Authors/Disclosures
Sian Lennon-Chrimes
PRESENTER 		No disclosure on file
No disclosure on file
Gaelle Klingelschmitt Gaelle Klingelschmitt has received personal compensation for serving as an employee of F.Hoffmann-La Roche LTD.
No disclosure on file
Veronica Anania, PhD (Genentech, Inc.) Dr. Anania has received personal compensation for serving as an employee of Genentech. Dr. Anania has stock in Roche.
Hajime Ito No disclosure on file
H.-Christian C. von Büdingen, MD, FÂ鶹´«Ã½Ó³»­ (F. Hoffmann-La Roche Ltd) Dr. von Büdingen has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd. Dr. von Büdingen has stock in F. Hoffmann-La Roche Ltd.