Treatment effects maintained over six years in patients with relapsing remitting multiple sclerosis

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Lemtrada is approved in more than 50 countries, with additional marketing applications under review by regulatory authorities globally. Positive new six-year investigational data from the extension study of Lemtrada^® (alemtuzumab) in patients with relapsing remitting multiple sclerosis (RRMS). These results will be presented today at the 32^nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in London.

In RRMS patients treated with Lemtrada in the CARE-MS Phase III pivotal studies, the effects described below observed in the two-year trials were maintained through four additional years in the extension study. More than 90 percent of the patients who were treated with Lemtrada in the CARE-MS trials enrolled in the extension. These patients were eligible to receive additional treatment with Lemtrada 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 percent of Lemtrada patients from CARE-MS I and 55 percent from CARE-MS II did not receive additional Lemtrada treatment during the following five years, through month 72.

• The low annualized relapse rates observed in patients who received Lemtrada 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 percent and 72 percent of patients who received Lemtrada 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 percent and 43 percent of patients who had disability before receiving Lemtrada 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 Lemtrada 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 percent or less, which was lower than what was observed in the Lemtrada-treated patients during the two-year pivotal studies (CARE-MS I: -0.59 percent in year one; -0.25 percent in year two; CARE-MS II: -0.48 percent in year one; -0.22 percent 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 (66 – 72 percent, CARE-MS I; 68 – 70 percent, CARE-MS II).

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 Lemtrada data being presented at ECTRIMS from the ongoing extension study illustrate that more than half of patients experiencedsustained effects of treatment on disease activity, despite receiving their last treatment course five years previously,” said Dr. Alasdair Coles, Professor, Department of Clinical Neurosciences, University of Cambridge.  “It is very promising to see these consistent effects over time across relapse, disability and MRI measures.”

The Phase III trials of Lemtrada were randomized, rater-blinded, two-year pivotal studies comparing treatment with Lemtrada 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 Lemtrada 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.

In clinical trials, serious side effects associated with Lemtrada included infusion reactions, autoimmune disorders (such as thyroid disease, autoimmune cytopenias, and nephropathies), infections and pneumonitis. Lemtrada may cause an increased risk of malignancies. Risk management programs incorporating education and monitoring help support early detection and management of key identified and potential risks. The most common side effects of Lemtrada are rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.