Contributions
Abstract: P1150
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: In patients with active relapsing-remitting multiple sclerosis (RRMS) and an inadequate response (≥1 relapse) to prior therapy at baseline (BL), alemtuzumab significantly reduced the annualised relapse rate (ARR), reduced the risk of confirmed disability worsening (CDW), and increased the proportion of patients with confirmed disability improvement (CDI) compared with subcutaneous interferon beta-1a over 2 years (CARE-MS II; NCT00548405). In an extension study (NCT00930553), efficacy has been shown to be durable through 5 years in the absence of continuous treatment.
Goal: To evaluate 6-year efficacy and safety of alemtuzumab in patients with an inadequate response to prior therapy.
Methods: CARE-MS II patients received 2 treatment courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days); patients who completed CARE-MS II could enter the extension, with as-needed alemtuzumab retreatment for relapse or MRI activity. Another disease-modifying therapy could be provided per investigator discretion. Assessments: ARR, proportion of patients free from 6-month CDW (≥1-point EDSS increase [≥1.5-point if BL EDSS=0]), 6-month CDI (≥1-point EDSS decrease [BL score ≥2.0]), no evidence of disease activity (NEDA), and adverse events (AEs).
Results: Through 6 years, 344/393 (88%) who enrolled in the extension remained on study. A low ARR was maintained through the extension (Year 6: 0.15). Through 6 years, 72% of patients were free from 6-month CDW, and 43% achieved 6-month CDI. Mean EDSS increased from BL by 0.10 over Years 0-6; the proportion of patients with improved or stable EDSS remained high (77% at Year 6). In each year, most patients achieved NEDA (60% at Year 6). These efficacy results were achieved with 50% of patients receiving no additional treatment after their initial 2 courses of alemtuzumab. The overall rate of AEs decreased over time. Thyroid AEs peaked at Year 3 and subsequently declined. Infusion-associated reactions decreased with additional treatment courses. The serious AE rate was low, including rate of serious infections, throughout the extension.
Conclusion: Alemtuzumab efficacy was maintained over 6 years in patients who had an inadequate response to prior therapy. 50% of patients received no additional treatment after the initial 2 courses of alemtuzumab. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for RRMS patients.
Disclosure:
STUDY SUPPORT: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
EJF: Consulting and/or speaking fees, and grant research support (Acorda, Bayer, Biogen, Chugai, Eli Lilly, EMD Serono, Genentech, Novartis, Opexa, Roche, Sanofi, Sanofi Genzyme, and Teva Pharmaceuticals).
RA: Speaker honoria, scientific advisory boards, and research grants (Bayer, Biogen, Biologix, Genpharm, GSK, Lundbeck, Merck Serono, Novartis, and Sanofi Genzyme).
DB: Compensation for advisory board participation, lecture, and travel (Bayer, Biogen, Merck, Sanofi Genzyme, and Teva).
SB: Honoraria for participation in advisory boards (Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi Genzyme); conference travel sponsorship (Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi Genzyme); speaker honoraria (Biogen and Genzyme); and unencumbered research grant (Biogen).
JAC: Consulting and/or speaking fees (Genentech, Novartis, and Sanofi Genzyme); and compensation for serving as a journal editor, associate editor, or member of an editorial advisory board (Multiple Sclerosis Journal: Experimental, Translational and Clinical).
H-PH: Consulting and/or speaking fees (Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme).
EH: Honoraria and grant support (Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi Genzyme, and Teva), and supported by Ministry of Education of Czech Republic.
COG: Speaker honoraria and compensation for consulting services (Alexion, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
KWS: Consulting and/or speaking fees (Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Synthon).
BS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Pfizer, Novartis, Sanofi Genzyme and Teva), and research support (Acorda, Biogen, MedImmune, Novartis, Roche and Sanofi Genzyme).
PV: Consulting and/or speaking fees, and research support (Almirall, Bayer, Biogen, GlaxoSmithKline, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
SW: Consultant, principal investigator, and/or speaker fees (Alkermes, Bayer, Biogen, EMD Serono, Genentech/Roche, Novartis, Sanofi Genzyme, Teva).
DHM, KT and MC: Employees of Sanofi Genzyme.
AJC: Consulting fees, grant support, and lecture fees (Bayer Schering Pharma and Sanofi Genzyme) on behalf of the University of Cambridge; and personal remuneration for lecture fees from July 2014.
Abstract: P1150
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: In patients with active relapsing-remitting multiple sclerosis (RRMS) and an inadequate response (≥1 relapse) to prior therapy at baseline (BL), alemtuzumab significantly reduced the annualised relapse rate (ARR), reduced the risk of confirmed disability worsening (CDW), and increased the proportion of patients with confirmed disability improvement (CDI) compared with subcutaneous interferon beta-1a over 2 years (CARE-MS II; NCT00548405). In an extension study (NCT00930553), efficacy has been shown to be durable through 5 years in the absence of continuous treatment.
Goal: To evaluate 6-year efficacy and safety of alemtuzumab in patients with an inadequate response to prior therapy.
Methods: CARE-MS II patients received 2 treatment courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days); patients who completed CARE-MS II could enter the extension, with as-needed alemtuzumab retreatment for relapse or MRI activity. Another disease-modifying therapy could be provided per investigator discretion. Assessments: ARR, proportion of patients free from 6-month CDW (≥1-point EDSS increase [≥1.5-point if BL EDSS=0]), 6-month CDI (≥1-point EDSS decrease [BL score ≥2.0]), no evidence of disease activity (NEDA), and adverse events (AEs).
Results: Through 6 years, 344/393 (88%) who enrolled in the extension remained on study. A low ARR was maintained through the extension (Year 6: 0.15). Through 6 years, 72% of patients were free from 6-month CDW, and 43% achieved 6-month CDI. Mean EDSS increased from BL by 0.10 over Years 0-6; the proportion of patients with improved or stable EDSS remained high (77% at Year 6). In each year, most patients achieved NEDA (60% at Year 6). These efficacy results were achieved with 50% of patients receiving no additional treatment after their initial 2 courses of alemtuzumab. The overall rate of AEs decreased over time. Thyroid AEs peaked at Year 3 and subsequently declined. Infusion-associated reactions decreased with additional treatment courses. The serious AE rate was low, including rate of serious infections, throughout the extension.
Conclusion: Alemtuzumab efficacy was maintained over 6 years in patients who had an inadequate response to prior therapy. 50% of patients received no additional treatment after the initial 2 courses of alemtuzumab. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for RRMS patients.
Disclosure:
STUDY SUPPORT: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
EJF: Consulting and/or speaking fees, and grant research support (Acorda, Bayer, Biogen, Chugai, Eli Lilly, EMD Serono, Genentech, Novartis, Opexa, Roche, Sanofi, Sanofi Genzyme, and Teva Pharmaceuticals).
RA: Speaker honoria, scientific advisory boards, and research grants (Bayer, Biogen, Biologix, Genpharm, GSK, Lundbeck, Merck Serono, Novartis, and Sanofi Genzyme).
DB: Compensation for advisory board participation, lecture, and travel (Bayer, Biogen, Merck, Sanofi Genzyme, and Teva).
SB: Honoraria for participation in advisory boards (Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi Genzyme); conference travel sponsorship (Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi Genzyme); speaker honoraria (Biogen and Genzyme); and unencumbered research grant (Biogen).
JAC: Consulting and/or speaking fees (Genentech, Novartis, and Sanofi Genzyme); and compensation for serving as a journal editor, associate editor, or member of an editorial advisory board (Multiple Sclerosis Journal: Experimental, Translational and Clinical).
H-PH: Consulting and/or speaking fees (Bayer, Biogen, CSL Behring, Grifols, Merck Serono, Novartis, Roche, and Sanofi Genzyme).
EH: Honoraria and grant support (Actelion, Biogen, Merck Serono, Novartis, Receptos, Roche, Sanofi Genzyme, and Teva), and supported by Ministry of Education of Czech Republic.
COG: Speaker honoraria and compensation for consulting services (Alexion, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva).
KWS: Consulting and/or speaking fees (Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Synthon).
BS: Speaking and/or consulting (Acorda, Bayer, Biogen, EMD Serono, Genentech, Pfizer, Novartis, Sanofi Genzyme and Teva), and research support (Acorda, Biogen, MedImmune, Novartis, Roche and Sanofi Genzyme).
PV: Consulting and/or speaking fees, and research support (Almirall, Bayer, Biogen, GlaxoSmithKline, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
SW: Consultant, principal investigator, and/or speaker fees (Alkermes, Bayer, Biogen, EMD Serono, Genentech/Roche, Novartis, Sanofi Genzyme, Teva).
DHM, KT and MC: Employees of Sanofi Genzyme.
AJC: Consulting fees, grant support, and lecture fees (Bayer Schering Pharma and Sanofi Genzyme) on behalf of the University of Cambridge; and personal remuneration for lecture fees from July 2014.