Contributions
Abstract: P1149
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Ozanimod (OZ) is an oral, selective sphingosine 1-phosphate receptor modulator (S1P1R/5R) in clinical development to treat relapsing MS.
Objectives: Characterize 1-year (48 Week) and 2-year (96 Week) efficacy and safety of low (LD, 0.5 mg) and high (HD, 1 mg) dose OZ in the ongoing blinded extension.
Methods: RADIANCE is an ongoing combined Phase 2/3 trial. Results of the 24-wk, placebo (PBO)-controlled, Phase 2 demonstrated efficacy of both LD and HD with good safety and tolerability (Lancet Neurol 2016). Patients originally randomized to OZ continued their assigned dose (LD, n=85; HD, n=81) and PBO patients were randomized 1:1 to LD (n=41) or HD (n=42).
Results: 224 of 249 patients (90%) entering the extension completed the Wk 96 visit; 5 patients discontinued due to an AE. By the end of Extension Year 1, the original PBO-treated pts had accumulated similar clinical benefits as the OZ-treated patients, so the data were pooled. The LD and HD groups showed a dose-dependent trend on reducing mean±SD Gadolinium-enhancing (GdE) lesions at Wk 48 (0.4±1.6 and 0.1±0.5) and Wk 96 (0.3±1.3 and 0.1±0.5), and new/enlarging T2 lesions at Wk 48 (1.3±3.7 and 0.7±3.8) and Wk 96 (1.8±4.4 and 0.6±1.2), respectively. The proportion of patients GdE lesion-free were comparable at Wk 96 for both doses (91% and 89%, respectively). Effect on unadjusted annualized relapse rate was maintained in the LD and HD groups: Wk 48 (0.26 and 0.15) and Wk 96 (0.3 and 0.19). No evidence of disease activity (no GdE or new/enlarging T2 lesions at Wk 48/96, and no relapse or increase in EDSS by Wk 48/96) was achieved in the LD (44% and 39%) and HD (62% and 47%) during years 1 and 2, respectively.
The AE profiles were comparable across groups. 20 patients experienced serious AEs, none considered related to OZ. The most common AEs continued to be minor infections and headache, with a single AE of bradycardia reported in a LD patient. No events of ≥2nd degree AV block or cases of macular edema were reported. Alanine aminotransferase ≥3x upper limit of normal occurred in 16 patients (6.4%), with 12/16 continuing to receive study drug, and none satisfying Hy"s law.
Conclusions: Both doses of ozanimod demonstrated efficacy over 48 and 96 weeks on MRI and clinical measures of MS disease activity in patients continuing ozanimod and those switching from PBO. The tolerability and safety results suggest a favorable risk-benefit profile that support the ongoing Phase 3 RADIANCE and SUNBEAM trials.
Disclosure:
J.A. Cohen: EMD Serono, Genentech, Innate Immunotherapeutics, Receptos, Vaccinex.
K. Selmaj: Genzyme, Novartis, Ono, Roche, Synthon, Teva, Biogen Idec, Merck, Receptos.
D.L. Arnold: Acorda, Bayer, Biogen Idec, Eli Lilly, Serono, Genentech,, Genzyme, GSK, Medimmune, Novartis, Opexa Therapeutics, Receptos, Roche, Sanofi-Aventis, Teva, the Canadian Institutes of Health Research, Multiple Sclerosis Society of Canada.
G. Comi: Almirall, Bayer, Chugai, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation, Teva, Almirall, Bayer
A. Bar-Or: Amplimmune, Aventis, Bayhill Therapeutics, Berlex/Bayer, Biogen Idec,, BioMS, Diogenix, Eli-Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, Guthy-Jackson/GGF, Medimmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche, Sanofi Aventis, Teva, Wyeth.
Mr. Allan Olson is an employee of Celgene.
Mr. Jeff Kopicko is an employee of Celgene.
Mr. Matt Cravets is an employee of Celgene.
Mr. Paul Frohna is an employee of Celgene.
Abstract: P1149
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Ozanimod (OZ) is an oral, selective sphingosine 1-phosphate receptor modulator (S1P1R/5R) in clinical development to treat relapsing MS.
Objectives: Characterize 1-year (48 Week) and 2-year (96 Week) efficacy and safety of low (LD, 0.5 mg) and high (HD, 1 mg) dose OZ in the ongoing blinded extension.
Methods: RADIANCE is an ongoing combined Phase 2/3 trial. Results of the 24-wk, placebo (PBO)-controlled, Phase 2 demonstrated efficacy of both LD and HD with good safety and tolerability (Lancet Neurol 2016). Patients originally randomized to OZ continued their assigned dose (LD, n=85; HD, n=81) and PBO patients were randomized 1:1 to LD (n=41) or HD (n=42).
Results: 224 of 249 patients (90%) entering the extension completed the Wk 96 visit; 5 patients discontinued due to an AE. By the end of Extension Year 1, the original PBO-treated pts had accumulated similar clinical benefits as the OZ-treated patients, so the data were pooled. The LD and HD groups showed a dose-dependent trend on reducing mean±SD Gadolinium-enhancing (GdE) lesions at Wk 48 (0.4±1.6 and 0.1±0.5) and Wk 96 (0.3±1.3 and 0.1±0.5), and new/enlarging T2 lesions at Wk 48 (1.3±3.7 and 0.7±3.8) and Wk 96 (1.8±4.4 and 0.6±1.2), respectively. The proportion of patients GdE lesion-free were comparable at Wk 96 for both doses (91% and 89%, respectively). Effect on unadjusted annualized relapse rate was maintained in the LD and HD groups: Wk 48 (0.26 and 0.15) and Wk 96 (0.3 and 0.19). No evidence of disease activity (no GdE or new/enlarging T2 lesions at Wk 48/96, and no relapse or increase in EDSS by Wk 48/96) was achieved in the LD (44% and 39%) and HD (62% and 47%) during years 1 and 2, respectively.
The AE profiles were comparable across groups. 20 patients experienced serious AEs, none considered related to OZ. The most common AEs continued to be minor infections and headache, with a single AE of bradycardia reported in a LD patient. No events of ≥2nd degree AV block or cases of macular edema were reported. Alanine aminotransferase ≥3x upper limit of normal occurred in 16 patients (6.4%), with 12/16 continuing to receive study drug, and none satisfying Hy"s law.
Conclusions: Both doses of ozanimod demonstrated efficacy over 48 and 96 weeks on MRI and clinical measures of MS disease activity in patients continuing ozanimod and those switching from PBO. The tolerability and safety results suggest a favorable risk-benefit profile that support the ongoing Phase 3 RADIANCE and SUNBEAM trials.
Disclosure:
J.A. Cohen: EMD Serono, Genentech, Innate Immunotherapeutics, Receptos, Vaccinex.
K. Selmaj: Genzyme, Novartis, Ono, Roche, Synthon, Teva, Biogen Idec, Merck, Receptos.
D.L. Arnold: Acorda, Bayer, Biogen Idec, Eli Lilly, Serono, Genentech,, Genzyme, GSK, Medimmune, Novartis, Opexa Therapeutics, Receptos, Roche, Sanofi-Aventis, Teva, the Canadian Institutes of Health Research, Multiple Sclerosis Society of Canada.
G. Comi: Almirall, Bayer, Chugai, Excemed, Genzyme, Merck Serono, Novartis, Receptos, Sanofi, Serono Symposia International Foundation, Teva, Almirall, Bayer
A. Bar-Or: Amplimmune, Aventis, Bayhill Therapeutics, Berlex/Bayer, Biogen Idec,, BioMS, Diogenix, Eli-Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, Guthy-Jackson/GGF, Medimmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche, Sanofi Aventis, Teva, Wyeth.
Mr. Allan Olson is an employee of Celgene.
Mr. Jeff Kopicko is an employee of Celgene.
Mr. Matt Cravets is an employee of Celgene.
Mr. Paul Frohna is an employee of Celgene.