Contributions
Abstract: P679
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: In phase 2 (CAMMS223; NCT00050778) and 3 (CARE-MS I [NCT00530348]; CARE-MS II [NCT00548405]) trials, alemtuzumab improved clinical and MRI outcomes in relapsing-remitting MS (RRMS) patients versus subcutaneous interferon beta-1a. An extension study (NCT00930553) demonstrated durable efficacy of alemtuzumab in the absence of continuous treatment up to 10 years.
Goal: To evaluate efficacy and safety of alemtuzumab over 10 years in patients from CAMMS223 enrolled in the extension.
Methods: In CAMMS223, patients with ≥2 relapses during the previous 2 years, Expanded Disability Status Scale (EDSS) score ≤3, and ≥1 Gd-enhancing (Gd+) lesion at baseline (BL) received 2 courses of alemtuzumab 12mg (Month 0: 5 days; Month 12: 3 days); a third course was possible based on T-cell counts. Patients could participate in an extended follow-up period, and then enroll in the extension with as-needed alemtuzumab retreatment for relapse or MRI activity. Another DMT could be provided per investigator discretion. Assessments: annualized relapse rate (ARR), EDSS, 6-month confirmed disability worsening [CDW: ≥1-point EDSS increase; ≥1.5-point if BL EDSS=0]), Gd+ lesions, lymphocyte counts, and AEs.
Results: Of 108 alemtuzumab-treated patients in CAMMS223, 60 entered the extension; 57 (95%) remained on study at Year 10. Over 10 years, 20 (33%) of patients received only 2 courses of alemtuzumab; 26 (43%), 7 (12%) and 6 (10%) received 3, 4 and 5 courses, respectively. Lymphocytes were depleted and then repopulated above the lower limit of normal after each treatment course. Through 10 years, ARR remained low (0.08), mean EDSS change from BL to Year 10 was +0.12, 78% had stable (≤0.5-point change) or improved (≥1-point improvement) EDSS, and 76% had no evidence of 6-month CDW. Over Years 1, 2, and 3 of the extension, most patients had no Gd+ lesions (Extension BL: 92%; Year 1: 94%; Year 2: 87%; Year 3: 95%). The most common AEs, infusion-associated reactions, decreased with additional courses. No patients withdrew due to AEs. Serious AE rate was low. The rate of thyroid AEs peaked at Year 3 and declined thereafter.
Conclusion: Alemtuzumab demonstrated durable clinical efficacy through Year 10, with most patients receiving ≤3 treatment courses. Safety findings were consistent with other alemtuzumab trials. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for patients with RRMS.
Disclosure:
Study support: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
KWS: Consulting and/or speaking fees (Biogen, Roche, Merck, Synthon, Sanofi Genzyme, Novartis).
MH: Nothing to disclose.
AB: Consulting fees/fees for non CME services from commercial interest or their agents/ grant and Research Support (Biogen, Mallinckrodt, Novartis, Roche-Genentech, Sanofi Genzyme, Teva Neuroscience).
DB: Advisory board participant, lecture and travel (Bayer, Biogen, Merck, Sanofi Genzyme, and Teva).
VB: Nothing to disclose.
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.
AV: Nothing to disclose.
SW: Consultant, principle investigator, and/or speaker (Alkermes, Bayer, Biogen, EMD Serono, Novartis, Roche-Genentech, Sanofi Genzyme, Teva).
DHM, KT, and MC: are employees of Sanofi Genyme.
LK: Compensation as a statistical consultant (Sanofi Genzyme).
EF: Consultancy fees, honoraria, travel, and research support (Acorda, Bayer Healthcare, Biogen, Eli Lilly, EMD Serono, Novartis, Opexa Therapeutics, Roche-Genentech, Sanofi Genzyme, and Teva).
Abstract: P679
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: In phase 2 (CAMMS223; NCT00050778) and 3 (CARE-MS I [NCT00530348]; CARE-MS II [NCT00548405]) trials, alemtuzumab improved clinical and MRI outcomes in relapsing-remitting MS (RRMS) patients versus subcutaneous interferon beta-1a. An extension study (NCT00930553) demonstrated durable efficacy of alemtuzumab in the absence of continuous treatment up to 10 years.
Goal: To evaluate efficacy and safety of alemtuzumab over 10 years in patients from CAMMS223 enrolled in the extension.
Methods: In CAMMS223, patients with ≥2 relapses during the previous 2 years, Expanded Disability Status Scale (EDSS) score ≤3, and ≥1 Gd-enhancing (Gd+) lesion at baseline (BL) received 2 courses of alemtuzumab 12mg (Month 0: 5 days; Month 12: 3 days); a third course was possible based on T-cell counts. Patients could participate in an extended follow-up period, and then enroll in the extension with as-needed alemtuzumab retreatment for relapse or MRI activity. Another DMT could be provided per investigator discretion. Assessments: annualized relapse rate (ARR), EDSS, 6-month confirmed disability worsening [CDW: ≥1-point EDSS increase; ≥1.5-point if BL EDSS=0]), Gd+ lesions, lymphocyte counts, and AEs.
Results: Of 108 alemtuzumab-treated patients in CAMMS223, 60 entered the extension; 57 (95%) remained on study at Year 10. Over 10 years, 20 (33%) of patients received only 2 courses of alemtuzumab; 26 (43%), 7 (12%) and 6 (10%) received 3, 4 and 5 courses, respectively. Lymphocytes were depleted and then repopulated above the lower limit of normal after each treatment course. Through 10 years, ARR remained low (0.08), mean EDSS change from BL to Year 10 was +0.12, 78% had stable (≤0.5-point change) or improved (≥1-point improvement) EDSS, and 76% had no evidence of 6-month CDW. Over Years 1, 2, and 3 of the extension, most patients had no Gd+ lesions (Extension BL: 92%; Year 1: 94%; Year 2: 87%; Year 3: 95%). The most common AEs, infusion-associated reactions, decreased with additional courses. No patients withdrew due to AEs. Serious AE rate was low. The rate of thyroid AEs peaked at Year 3 and declined thereafter.
Conclusion: Alemtuzumab demonstrated durable clinical efficacy through Year 10, with most patients receiving ≤3 treatment courses. Safety findings were consistent with other alemtuzumab trials. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for patients with RRMS.
Disclosure:
Study support: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.
KWS: Consulting and/or speaking fees (Biogen, Roche, Merck, Synthon, Sanofi Genzyme, Novartis).
MH: Nothing to disclose.
AB: Consulting fees/fees for non CME services from commercial interest or their agents/ grant and Research Support (Biogen, Mallinckrodt, Novartis, Roche-Genentech, Sanofi Genzyme, Teva Neuroscience).
DB: Advisory board participant, lecture and travel (Bayer, Biogen, Merck, Sanofi Genzyme, and Teva).
VB: Nothing to disclose.
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.
AV: Nothing to disclose.
SW: Consultant, principle investigator, and/or speaker (Alkermes, Bayer, Biogen, EMD Serono, Novartis, Roche-Genentech, Sanofi Genzyme, Teva).
DHM, KT, and MC: are employees of Sanofi Genyme.
LK: Compensation as a statistical consultant (Sanofi Genzyme).
EF: Consultancy fees, honoraria, travel, and research support (Acorda, Bayer Healthcare, Biogen, Eli Lilly, EMD Serono, Novartis, Opexa Therapeutics, Roche-Genentech, Sanofi Genzyme, and Teva).