Contributions
Abstract: P911
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Background: Siponimod, an oral, selective sphingosine-1-phosphate (S1P1,5) receptor modulator, showed efficacy/safety recently in secondary progressive MS (Phase 3
EXPAND) and previously in relapsing MS (Phase 2 BOLD) populations.
Objective: To assess the longer-term safety of siponimod treatment for up to 6 years in MS patients (pts) using pooled data from the BOLD and EXPAND core/extensions trials.
Methods: Pooled safety data were evaluated in 2 groups: a controlled pool (CP) of pts who received siponimod 2mg (N=1148) and placebo (PBO; N=607) during the core
phase of PBO-controlled studies; a long-term pool (LP) of pts who received ≥1 dose of
siponimod 2 or 10mg in core/extension phases (N=1737) - data collected includes pts on any siponimod dose 0.25, 0.5, 1.25, 2, or 10mg in core phase BOLD and switched to 2mg in extension phase. Analysis included adverse events (AEs), serious AEs (SAEs), and AEs of special interest with S1P modulators. The relation of infections and lymphocyte counts was analysed in the EXPAND trial. All safety outcomes are
presented as incidences or incidence rates (IRs)/100 patient-years (PYs).
Results: In the CP, mean exposure to siponimod 2 mg was 17.7 months (1696 PYs) and 16.5 months (835 PYs) for PBO. As of May 2017, mean exposure in the LP was 27.8 months (4018 PYs); 127 pts were exposed for ≥5 years. In the LP, AEs were reported in 90% of pts, SAEs in 20.7%, and AEs that led to study discontinuation in 9.6%. IRs of the most common AEs (incidence ≥10%) in the LP were consistent with
those reported with siponimod 2mg in the CP: nasopharyngitis (9.1 vs 9.7), headache
(7.9 vs 11.3), urinary tract infection (UTI; 6.9 vs 8.3), fall (5.5 vs 7.9), and hypertension (4.9 vs 7.4). IRs of infections were 43.2 in the LP and 48.9 for siponimod 2mg and 53.8 for PBO in the CP; nasopharyngitis and UTI were the most common infections. No
increase in IRs of oral herpes (1.2 vs 1.1), herpes simplex (0.2 vs 0.2), and varicella zoster virus infections (1.8 vs 1.9) was observed in LP versus CP. Among pts with ≥1
measured lymphocyte count < 0.4×109/L at any time, 53% had any infection, 44.7% in
the 0.4-0.6×109/L and 42.3% in the >0.6×109/L categories similar/lower to the rate in the PBO (49.8%). IRs of malignancies were similar in CP and LP (1.2).
Conclusions: Longer-term follow-up treatment with siponimod 2 mg did not reveal any
increase in IR of AEs or new safety findings versus the CP. Low lymphocyte counts
were not associated with an increased infection rate.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Ludwig Kappos' Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
Patrick Vermersch has received honoraria and consulting fees from Biogen, Genzyme-Sanofi, Bayer, Novartis, Merck, GSK and Almirall, and research support from Biogen, Genzyme-Sanofi, Bayer, and Merck.
Robert Fox has received compensation for serving as a consultant or speaker from Allozyne, Avanir, Biogen, Novartis, Questcor and Teva Pharmaceutical Industries. He, or the institution he works for, has received research support from Novartis.
Amit Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from: Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, MAPI, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme.
Bruce Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, GeNeuro, Novartis, and Sanofi Genzyme.
Gavin Giovannoni is a steering committee member on the daclizumab trials for AbbVie, the BG12 and daclizumab trials for Biogen, the fingolimod and siponimod trials for Novartis, the laquinimod trials for Teva and the ocrelizumab trials for Roche. He has also received consultancy fees for advisory board meetings for oral cladribine trials for Merck, Genzyme-Sanofi, and in relation to DSMB activities for Synthon BV, as well as honoraria for speaking at the Physicians' summit and several medical education meetings. He is also the Co-Chief Editor of Multiple Sclerosis and Related Disorders (Elsevier).
Ralf Gold has received compensation for serving as a consultant or speaker from Bayer HealthCare, Biogen, Merck, Novartis and Teva. He, or the institution he works for, has received research support from Bayer HealthCare, Biogen, Merck, Novartis and Teva; he has also received honoraria as a Journal Editor from SAGE and Thieme Verlag.
Tomasz Masior, Daniela Piani Meier, Davorka Tomic, Frank Dahlke, Goeril Karlsson, Nicolas Rouyrre, and Ajay Kilaru are employees of Novartis.
Abstract: P911
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Background: Siponimod, an oral, selective sphingosine-1-phosphate (S1P1,5) receptor modulator, showed efficacy/safety recently in secondary progressive MS (Phase 3
EXPAND) and previously in relapsing MS (Phase 2 BOLD) populations.
Objective: To assess the longer-term safety of siponimod treatment for up to 6 years in MS patients (pts) using pooled data from the BOLD and EXPAND core/extensions trials.
Methods: Pooled safety data were evaluated in 2 groups: a controlled pool (CP) of pts who received siponimod 2mg (N=1148) and placebo (PBO; N=607) during the core
phase of PBO-controlled studies; a long-term pool (LP) of pts who received ≥1 dose of
siponimod 2 or 10mg in core/extension phases (N=1737) - data collected includes pts on any siponimod dose 0.25, 0.5, 1.25, 2, or 10mg in core phase BOLD and switched to 2mg in extension phase. Analysis included adverse events (AEs), serious AEs (SAEs), and AEs of special interest with S1P modulators. The relation of infections and lymphocyte counts was analysed in the EXPAND trial. All safety outcomes are
presented as incidences or incidence rates (IRs)/100 patient-years (PYs).
Results: In the CP, mean exposure to siponimod 2 mg was 17.7 months (1696 PYs) and 16.5 months (835 PYs) for PBO. As of May 2017, mean exposure in the LP was 27.8 months (4018 PYs); 127 pts were exposed for ≥5 years. In the LP, AEs were reported in 90% of pts, SAEs in 20.7%, and AEs that led to study discontinuation in 9.6%. IRs of the most common AEs (incidence ≥10%) in the LP were consistent with
those reported with siponimod 2mg in the CP: nasopharyngitis (9.1 vs 9.7), headache
(7.9 vs 11.3), urinary tract infection (UTI; 6.9 vs 8.3), fall (5.5 vs 7.9), and hypertension (4.9 vs 7.4). IRs of infections were 43.2 in the LP and 48.9 for siponimod 2mg and 53.8 for PBO in the CP; nasopharyngitis and UTI were the most common infections. No
increase in IRs of oral herpes (1.2 vs 1.1), herpes simplex (0.2 vs 0.2), and varicella zoster virus infections (1.8 vs 1.9) was observed in LP versus CP. Among pts with ≥1
measured lymphocyte count < 0.4×109/L at any time, 53% had any infection, 44.7% in
the 0.4-0.6×109/L and 42.3% in the >0.6×109/L categories similar/lower to the rate in the PBO (49.8%). IRs of malignancies were similar in CP and LP (1.2).
Conclusions: Longer-term follow-up treatment with siponimod 2 mg did not reveal any
increase in IR of AEs or new safety findings versus the CP. Low lymphocyte counts
were not associated with an increased infection rate.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Ludwig Kappos' Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
Patrick Vermersch has received honoraria and consulting fees from Biogen, Genzyme-Sanofi, Bayer, Novartis, Merck, GSK and Almirall, and research support from Biogen, Genzyme-Sanofi, Bayer, and Merck.
Robert Fox has received compensation for serving as a consultant or speaker from Allozyne, Avanir, Biogen, Novartis, Questcor and Teva Pharmaceutical Industries. He, or the institution he works for, has received research support from Novartis.
Amit Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from: Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, MAPI, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme.
Bruce Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, GeNeuro, Novartis, and Sanofi Genzyme.
Gavin Giovannoni is a steering committee member on the daclizumab trials for AbbVie, the BG12 and daclizumab trials for Biogen, the fingolimod and siponimod trials for Novartis, the laquinimod trials for Teva and the ocrelizumab trials for Roche. He has also received consultancy fees for advisory board meetings for oral cladribine trials for Merck, Genzyme-Sanofi, and in relation to DSMB activities for Synthon BV, as well as honoraria for speaking at the Physicians' summit and several medical education meetings. He is also the Co-Chief Editor of Multiple Sclerosis and Related Disorders (Elsevier).
Ralf Gold has received compensation for serving as a consultant or speaker from Bayer HealthCare, Biogen, Merck, Novartis and Teva. He, or the institution he works for, has received research support from Bayer HealthCare, Biogen, Merck, Novartis and Teva; he has also received honoraria as a Journal Editor from SAGE and Thieme Verlag.
Tomasz Masior, Daniela Piani Meier, Davorka Tomic, Frank Dahlke, Goeril Karlsson, Nicolas Rouyrre, and Ajay Kilaru are employees of Novartis.