Gains in Disease-related Disability Seen with Alemtuzumab in Patients with Multiple Sclerosis

Copenhagen, Denmark — October 3, 2013 – Patients with relapsing-remitting multiple sclerosis (RRMS) who received alemtuzumab for two years demonstrated an improvement in their disease-related disability that was reflected in better mean Expanded Disability Status Scale (EDSS) scores compared to their own baseline and to the scores of similar patients who received treatment with subcutaneous interferon beta-1a. This reduction was observed as early as six months and was both sustained and improved upon during a two year follow-up period. Alemtuzumab is a humanized monoclonal antibody targeting the cell-surface glycoprotein CD52 that has demonstrated immunomodulatory effects, possibly affected by depleting and regenerating the lymphocyte population.

Findings were presented on October 3 during the Treatment of Specific Symptoms session of the 29^th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the 18^th Annual Conference of Rehabilitation in MS.

Vesna V. Brinar, MD, PhD, of the School of Medicine and University Hospital Centre Zagreb in Zagreb, Croatia, and colleagues conducted the CARE-MS II study, a randomized, rater-blinded, active controlled, head to head comparison, phase 3 trial that compared patient outcome following treatment with alemtuzumab or interferon beta-1a in patients with RRMS who continued to show disease activity after receiving disease-modifying therapy (DMT).

Outcome was evaluated by changes in the EDSS compared to each patient’s baseline scores at 6, 12, and 24 months. The EDSS quantifies disability in MS by measuring eight Functional Systems (FS), which allows a Functional System (FS) Score for each category (pyramidal, cerebellar, brain stem, sensory, bowel and bladder, visual, and cerebral) to be assigned. According to Brinar, changes in FS scores are important in the earlier stages of MS, when disability is manifested in areas other than walking ability.

Patients with a baseline EDSS score of 0.0 to 5.0 who experienced onset of MS symptoms within 10 years of screening and who had relapsed on prior therapy were enrolled and randomized to receive either alemtuzumab at 12 mg/day intravenously on five consecutive days at study start and on three consecutive days 12 months later, or interferon beta-1a by subcutaneous injection at 44 mcg three times weekly. Patient characteristics were well balanced in the two groups; in particular, 96.2% of patients treated with alemtuzumab compared to 97.5% of patients treated with interferon beta-1a had a baseline EDSS score greater than 1.

Evaluations of disability were done at baseline and at 6, 12, and 24 months for each FS score and showed that 426 alemtuzumab patients had larger mean reductions from baseline in all 7 FS scores and significantly improved cerebellar, cerebral, pyramidal, sensory, and visual scores at Month 24 than 202 patients in the interferon arm. Comparisons of the FS scores of the two treatment arms showed differences between the treatment groups that significantly favored alemtuzumab at Month 6 for cerebellar (P<0.0007) and sensory FS (P=0.0123) that were maintained throughout each time point (P<0.0001, P<0.0001 cerebellar; P=0.0107, P=0.0021 sensory at 12 and 24 months respectively).

Significant differences between treatment groups were seen at Month 24 for the cerebral (P=0.0004) pyramidal (P=0.0085).Statistically non-significant improvements were also recorded for the visual, brainstem and bowel/bladder FS scores.

“What we see is that patients who had already relapsed on other treatments were stabilized and their condition improved with alemtuzumab; patients improved on all FS parameters — at six months, there was a decrease in relapse rate, an improvement in EDSS and the rates of disability decreased,” said Brinar.

The implication of the improved scores is that disability was significantly more likely to be reversed with alemtuzumab than with interferon-1a in the CARE-MS II trial. According to Brinar, “These data suggest that regardless of the impairment a patient may have developed as a result of prior MS disease activity, improvement in pre-existing disability is more likely with alemtuzumab than with interferon beta-1a.”

The CARE-MS II study was funded by Genzyme, a Sanofi Company, and Bayer Healthcare Pharmaceuticals.