Genzyme presented additional data at the 64th Annual Meeting of the American Academy of Neurology from its Phase II CARE-MS II trial, which demonstrated that the Expanded Disability Status Scale (EDSS), i.e. a standard assessment of physical disability progression showed a considerably slower accumulation of disability in patients with multiple sclerosis (MS) who were treated with alemtuzumab, as compared with Rebif ®, a high dose subcutaneous interferon beta-1a.
Furthermore, some patients who were treated with alemtuzumab from baseline registered a substantial improvement in disability scores, compared with those who received Rebif, which indicates a reversal of disability in these patients. Patients with pre-existing disability who were administered with alemtuzumab in the trial were more than double as likely to achieve a sustained reduction in disability compared with those who took Rebif.
The CARE-MS II randomized Phase III clinical trial was designed to compare alemtuzumab, an investigational drug with Rebif, in patients with relapsing-remitting multiple sclerosis (RRMS) who relapsed during their previous treatment.
In November, Genzyme announced that the trial results for the co-primary endpoints were highly important statistically. The key disability data that was presented at the American Academy Of Neurology’s 64th Annual Meeting included that the average EDSS score for patients in the alemtuzumab group decreased over a period of 2 years to 0.17, suggesting an improvement in physical disability, whilst that of the Rebif group increased to 0.24, suggesting that their disability got worse. (p < 0.0001). 29% of patients in the alemtuzumab group experienced a six-month sustained reduction in disability in comparison, with just 13% in the Rebif group (p=0.0002) at 2-years. Over a 2-year study period, EDSS measured that those in the alemtuzumab group had a 42% reduction in the risk of six-month sustained accumulation (worsening) of disability (SAD) as compared with Rebif (p=0.0084), which represents a highly important statistical outcome for this co-primary endpoint. The study also demonstrated that 65% of patients in the alemtuzumab group remained relapse-free for the two years of the trial compared with 47% in the Rebif group (p
During the CARE-MS II trial, patients received 12mg of alemtuzumab via IV for a total of eight times during the course of the two-year study, with the first course being administered on five consecutive days, and the second course on three consecutive days 12 months later. Those in the Rebif group received 3 weekly 44 mcg subcutaneous Rebif injections each week for the entire 2-year duration of the study.
Leading researcher of the Phase II and III alemtuzumab’s clinical trials, Professor Alastair Compston, Head of the Department of Clinical Neurosciences at the University of Cambridge and Chair of the Steering Committee that oversees the study’s conduct declared:
“Alemtuzumab is the first disease modifying therapy to show a significant effect both on relapse and disability endpoints over and above those of Rebif in a comparative trial. The efficacy data from the CARE-MS trial program suggest that, if approved, alemtuzumab will be an important new treatment for relapsing MS patients with active disease.”
According to the additional new data of the CARE-MS II study, alemtuzumab offered a substantial improvement in various imaging endpoints that were consistent with the observed effects of the clinical endpoints in comparison with Rebif. Imaging is often used in people with MS to identify the development of lesions or areas of inflammation within the central nervous system (CNS).
As compared with Rebif, alemtuzumab achieved a statistically important improvement in the percentage of patients with new or enlarging T2-hyperintense lesions (46 vs. 68; p
With regard to adverse events, those most frequently observed in alemtuzumab during the CARE-MS Il study consisted of infusion-associated reactions that were generally mild to moderate.
Whilst infections were common amongst both groups, the incidence in the alemtuzumab group was noted to be higher, with the most common infections including upper respiratory and urinary tract infections, cutaneous fungal infections and oral herpes. 3.7% of those in the alemtuzumab group experienced serious infection, compared with 1.5% in the Rebif group. However, the severity of the infections was predominantly mild to moderate, with none proving fatal.
15.9% of participants in the alemtuzumab group developed an autoimmune adverse event linked to the thyroid as compared with 5.0% in the Rebif group, and 0.9% of those in the alemtuzumab group developed immune thrombocytopenia (ITP) over the 2-year study period. These incidents were identified sufficiently early in a monitoring program and controlled with conventional therapies. All Genzyme trials of alemtuzumab for the potential treatment of MS include patient monitoring for ITP and thyroid or renal disorders.
Alemtuzumab is a monoclonal antibody with minimal impact on other immune cells and selectively targets CD52, a protein abundant on T and B cells. It results in depleting the circulating T and B cells that are thought to be responsible for the damaging inflammatory process in MS.
Alemtuzumab’s acute anti-inflammatory effect follows immediately after the onset of a distinctive pattern of T and B cell repopulation, which continues over time and rebalances the individual’s immune system so it potentially reduces MS disease activity.
The company aims to apply for U.S. and EU approval of alemtuzumab in relapsing MS in the second quarter of 2012 under the name of LemtradaTM. Alemtuzumab must not be used in MS patients outside formal, regulated clinical trial settings with appropriate patient monitoring measures.
Written By Petra Rattue