Abstract Details

Title Adolescents with NMOSD Achieved Similar Exposures and Favorable Safety Profile when Treated with the Adult Satralizumab Dosing Regimen

Topic Autoimmune Neurology

Presentation(s) P14 - Poster Session 14 (8:00 AM-9:00 AM)

Poster/Presentation
Number 15-006

Objective

To describe satralizumab exposure in adolescents with neuromyelitis optica spectrum disorder (NMOSD) to support dose selection.

Background

Interleukin-6 (IL-6) is implicated in the immunopathology of NMOSD. Satralizumab, a humanized recycling monoclonal antibody that binds to the IL-6 receptor (IL-6R), demonstrated a reduction in NMOSD relapse risk in two phase 3 studies: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279).

Design/Methods Patients in both studies (N=178) received placebo or satralizumab 120mg at Weeks 0, 2 and 4, and every four weeks (Q4W) thereafter. Data on clinical and protocol-defined relapses (PDRs), aquaporin-4 autoantibody (AQP4-IgG) serostatus, safety endpoints, and pharmacokinetic (PK) and pharmacodynamic (PD) markers were evaluated in adolescent patients. A popPK model, developed using data from a Phase I satralizumab trial (healthy volunteers) and both Phase 3 studies, was used to analyse PK data.

Results Eight adolescent patients were enrolled in SAkuraSky (adolescents were not permitted in SAkuraStar). Seven were evaluated for efficacy (one patient had PK data only). The mean age was 15.4 years (range 13-17); mean weight (79.3kg [range 47.5-140.4]) was similar to the adult population. Six patients were female; three patients were AQP4-IgG seropositive.

The range of model-predicted exposures was similar to those in adults, correlating inversely with body weight, and not age. Treatment effects on soluble IL-6R levels, a marker of target engagement, were similar between adults and adolescents, with similar predicted median IL-6R occupancy (>95% maintained over the dose interval). One of four patients receiving satralizumab experienced a relapse (PDR, n=1); all three patients receiving placebo relapsed (PDR, n=1; clinical relapse, n=2). The safety profile of satralizumab in adolescents was consistent with the adult patient population; no new safety signals were identified.

Conclusions

These findings support the recommendation that adolescent patients with NMOSD receive the adult 120mg loading and Q4W maintenance regimen of satralizumab.

Authors/Disclosures
Cheryl Hemingway PRESENTER	Cheryl Hemingway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Cheryl Hemingway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Cheryl Hemingway has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
	No disclosure on file
	No disclosure on file
Daniela Stokmaier	Daniela Stokmaier has received personal compensation for serving as an employee of Roche.
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, F�鶹��ýӳ�� (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.
Sian Lennon-Chrimes	No disclosure on file

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