Sanofi Genzyme has announced the presentation six-year investigational data from the extension study of Lemtrada (alemtuzumab) in patients with relapsing remitting multiple sclerosis (RRMS). These results were presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in London, UK.
“The Lemtrada data being presented at ECTRIMS from the ongoing extension study illustrate that more than half of patients experienced sustained effects of treatment on disease activity, despite receiving their last treatment course five years previously,” said Alasdair Coles, Department of Clinical Neurosciences, University of Cambridge, UK. “It is very promising to see these consistent effects over time across relapse, disability and MRI measures.”
In RRMS patients treated with alemtuzumab in the CARE-MS phase III pivotal studies, the effects observed in the two-year trials were maintained through four additional years in the extension study. More than 90% of the patients (349 (95%) CARE-MS I and 393 (93%) CARE-MS II) who were treated with alemtuzumab in the CARE-MS trials enrolled in the extension. These patients were eligible to receive additional treatment with alemtuzumab in the extension if they experienced at least one relapse or at least two new or enlarging brain or spinal cord lesions.
After the initial two courses of treatment in the CARE-MS trials, which were given at month zero and at month 12, 64% of alemtuzumab patients from CARE-MS I and 55% from CARE-MS II did not receive additional alemtuzumab treatment during the following five years, through month 72.
- The low annualised relapse rates observed in patients who received alemtuzumab in the phase III studies CARE-MS I (0.16) and CARE-MS II (0.28) remained consistent throughout the extension (0.12 and 0.15 at year six).
- Through year six, 77% (248 patients) and 72% of patients (219 patients) who received alemtuzumab in CARE-MS I and CARE-MS II, respectively, did not experience worsening of six-month confirmed disability as measured by the Expanded Disability Status Scale (EDSS).
- Through year six, 34% (126 patients) and 43% (119 patients) of patients who had disability before receiving alemtuzumab in CARE-MS I and CARE-MS II, respectively, had improvement in EDSS score confirmed over at least six months as compared with pre-treatment baseline.
- Through year six, patients who received alemtuzumab in CARE-MS I and II experienced a slowing of brain atrophy as measured by brain parenchymal fraction on magnetic resonance imaging (MRI). In years three through six, the median yearly brain volume loss was -0.20% or less, which was lower than that observed in the alemtuzumab-treated patients during the two-year pivotal studies (CARE-MS I: -0.59 percent in year one; -0.25% in year two; CARE-MS II: -0.48% in year one; -0.22% in year two).
- In each of years three, four, five and six, most patients had no evidence of MRI disease activity, defined as no new gadolinium-enhancing T1 lesions and no new or enlarging T2 lesions (CARE-MS I: Y3 72% n=326 patients, Y4 70% n=324 patients, Y5 70% n=319 patients, Y6 66% n=304 patients; CARE-MS II: Y3 68% n=361 patients, Y4 70% n=336 patients, Y5 68% n=326 patients, Y6 69% n=304 patients).
Through year six, the yearly incidence of most adverse events during the extension study was comparable or reduced compared with the pivotal studies. The frequency of thyroid adverse events was highest in year three and declined thereafter.
The phase III trials of alemtuzumab were randomised, rater-blinded, two-year pivotal studies comparing treatment with alemtuzumab to high-dose subcutaneous interferon beta-1a in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had an inadequate response to another therapy (CARE-MS II). Active disease was defined as at least two relapses in the previous two years and at least one in the previous year. The protocol called for alemtuzumab to be administered as two annual treatment courses, with the first treatment course administered via intravenous infusion on five consecutive days, and the second course administered on three consecutive days, 12 months later.