Durable Clinical Efficacy of Alemtuzumab in Patients With Active RRMS in the Absence of Continuous Treatment: 7-Year Follow-up of CARE-MS I Patients (TOPAZ Study) (P6.376)

Objective: Evaluate efficacy/safety of alemtuzumab over 7 years (y) in relapsing-remitting MS (RRMS) patients from CARE-MS I.

Background: In CARE-MS I (NCT00530348), alemtuzumab 12 mg/day (baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 y in treatment-naive RRMS patients. Durable efficacy was observed in a 4-y extension (NCT00930553; 95% enrolled, 92% completed), in which patients could receive alemtuzumab retreatment as-needed for relapse/MRI activity or receive other disease-modifying therapies (DMTs) per investigator’s discretion. Patients completing the extension could enroll in TOPAZ (n=321), a 5-y study (NCT02255656), for further evaluation.

Design/Methods: In TOPAZ, patients can receive alemtuzumab retreatment (≥12 months apart) or other DMTs at any time (both per investigator’s discretion). MRI scans are performed annually. Assessments: annualized relapse rate (ARR); 6-month confirmed disability worsening (CDW); 6-month confirmed disability improvement (CDI); no evidence of disease activity (NEDA); AEs.

Results: 299 patients (93%) completed Y1 of TOPAZ (Y7 after initiating alemtuzumab). ARR remained low (Y7: 0.13); 60% were relapse-free in Y3─7. The percentage of patients with stable/improved EDSS scores versus baseline remained high (Y7: 78%). At Y7, 74% were free from 6-month CDW, and 37% achieved 6-month CDI. The majority of patients achieved NEDA each year (Y7: 61%). 59% received no additional treatment (alemtuzumab or other DMT) after the initial 2 courses. Overall AE incidence, infusion-associated reactions, and infections decreased over time. Thyroid AE incidence peaked in Y3 (15%) and then declined.

Conclusions: Alemtuzumab efficacy was maintained for 7 y in treatment-naive patients, despite 59% receiving no additional treatment since the initial 2 courses. 37% of patients also showed improvement in disability. Alemtuzumab safety profile remained consistent; overall AE incidence decreased over time. Alemtuzumab may provide a unique treatment approach for RRMS patients, offering durable efficacy in the absence of continuous treatment.

Study Supported by: Sanofi and Bayer HealthCare Pharmaceuticals.

Disclosure: Dr. Vermersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen, Celgene, Merck, Novartis, Roche, Sanofi, Servier, and Teva. Dr. Vermersch has received research support from Almirall, Biogen, Celgene, Merck, Novartis, Roche, Sanofi, Servier, and Teva. Dr. Coles has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi. Dr. Boyko has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Biogen, Merck Serono, Novartis, Sanofi, and Teva. Dr. De Seze has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi. Dr. De Seze has received research support from Sanofi. Dr. Hartung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, GeNeuro, Sanofi Genzyme, Merck, Novartis Pharmaceuticals, Octapharma, Opexa Therapeutics, Teva Pharmaceuticals, MedImmune, Bayer HealthCare, Forward Pharma, and Roche. Dr. Havrdova has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Celgene, Merck, Novartis, Sanofi Genzyme and Teva. Dr. Inshasi has nothing to disclose. Dr. McCombe has nothing to disclose. Dr. Montalban has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Oryzon, Roche, Sanofi and Teva Pharmaceutical. Dr. Pozzilli has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Biogen, Merck, Novartis, Sanofi, and Teva. Dr. Pozzilli has received research support from Actelion, Biogen, Merck, Novartis, Sanofi, and Teva. Dr. Selmaj has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Celgene, Novartis, Merck, Roche. Dr. Margolin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Melanson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Daizadeh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Rodriguez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Sanofi. Dr. Van Wijmeersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer-Schering, Biogen, Merck-Serono, Novartis, Roche, Sanofi Genzyme, and Teva. Dr. Van Wijmeersch has received research support from Bayer-Schering, Biogen, Merck-Serono, Novartis, Roche, Sanofi Genzyme, and Teva.