Sanofi and Genzyme:positive investigational data from the extension study of Lemtrada

Sanofi and its subsidiary Genzyme  announced positive new five-year investigational data from the extension study of Lemtrada (alemtuzumab) for patients with relapsing remitting multiple sclerosis (RRMS).

These results will be presented on October 9, 2015 at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain.

Companies stated that in RRMS patients treated with Lemtrada in the Phase III pivotal studies, the effects described below observed in the two-year trials were maintained through three additional years in the extension study (years three, four and five). After the initial two courses of treatment in the pivotal studies, which were given at month zero and at month 12, 68 percent of Lemtrada patients from CARE-MS I and 60 percent from CARE-MS II did not receive additional Lemtrada treatment during the following four years, through month 60.

The low annualized relapse rates observed in patients who received Lemtrada in CARE-MS I (0.18) and CARE-MS II (0.27) were maintained from year three (0.19 and 0.22) to year five (0.15 and 0.18).

Through year five, 80 percent and 76 percent of patients who received Lemtrada in CARE-MS I and CARE-MS II, respectively, did not experience worsening of disability progression confirmed over six months as measured by the Expanded Disability Status Scale (EDSS).

Through year five, 33 percent and 43 percent of patients who had some 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 five, patients who received Lemtrada in CARE-MS I and II experienced a slowing of brain volume loss as measured by brain parenchymal fraction on magnetic resonance imaging (MRI). In years three, four and five, the median yearly brain volume loss was -0.20 percent or less, which was lower than what was observed during the two-year pivotal studies.
In each of years three, four and five, most patients had no evidence of MRI disease activity (70 – 72 percent, CARE-MS I; 68 – 70 percent, CARE-MS II).

Through year five, the 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 Lemtrada were randomized, rater-blinded, two-year pivotal studies comparing treatment with Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif®) 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).

Companies added that more than 90 percent of the patients who were treated with Lemtrada in the CARE-MS Phase III trials enrolled in the extension study. These patients were eligible to receive additional treatment with Lemtrada in the extension study if they experienced at least one relapse or at least two new or enlarging brain or spinal cord lesions.

“These data illustrate that most Lemtrada patients experienced sustained effects of treatment, despite the absence of additional treatment courses,” said Professor Eva Havrdová, MD, PhD, MS Center, Department of Neurology, First Medical Faculty, Charles University, Prague, Czech Republic.

“It is encouraging to see consistent effects maintained across multiple meaningful outcomes through five years.”

In clinical trials, serious side effects associated with Lemtrada included infusion-associated reactions, autoimmune disorders (such as thyroid disease, autoimmune cytopenias, and nephropathies), infections and pneumonitis. 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. (See Important Safety Information below.)

“The five-year data announced today are exciting and important for people living with relapsing MS, because of Lemtrada’s potential to change the treatment approach for patients who continue to suffer from this debilitating disease, and for whom Lemtrada is an option,” said Bill Sibold, Head of Genzyme’s Multiple Sclerosis business.”

Companies concludet that in CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.