Date: 2012-10-31
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results from the Lemtrada® (alemtuzumab) CARE-MS I and CARE-MS II pivotal studies in in the November 1, 2012 online issue of The Lancet.
Company: Genzyme (USA - MA), a Sanofi company (France)
Product: Lemtrada® (alemtuzumab)
Action
mechanism: This humanized monoclonal antibody targets the cell-surface glycoprotein CD52, which is often expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab depletes the T- and B-cells that may be responsible for the cellular damage in multiple sclerosis, while potentially sparing other cells of the immune system. Early alemtuzumab research has also suggested a distinctive pattern of lymphocyte reconstitution in patients following treatment.
Disease: patients with relapsing-remitting multiple sclerosis (MS)
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country:
Trial
details: The CARE-MS trials are Phase III, global, randomized clinical trials designed to evaluate whether the investigational MS therapy Lemtrada® could achieve meaningful efficacy and safety improvements over the approved, active comparator Rebif ®(subcutaneous interferon beta-1a 44 mcg), a standard treatment for relapsing-remitting MS. The CARE-MS I study evaluated 581 patients naïve to prior MS treatment, except for steroids. The CARE-MS II study evaluated 840 patients who have had at least one relapse occurring while on MS therapy, including standard injectable disease modifying therapies. In both trials, Lemtrada® was given as an IV administration a total of eight times over the course of the two-year study. The first treatment course of Lemtrada® was administered on five consecutive days, and the second course was administered on three consecutive days 12 months later. Rebif 44 mcg was administered by subcutaneous injection three times per week, each week, throughout the two years of study.
Latest
news: Genzyme, a Sanofi company, has announced the publication of results from the Lemtrada® (alemtuzumab) CARE-MS I and CARE-MS II pivotal studies in patients with relapsing-remitting multiple sclerosis (MS) in the November 1, 2012 online issue of The Lancet. In CARE-MS I and CARE-MS II, Lemtrada® was significantly more effective at reducing annualized relapse rates than the active comparator Rebif® (high dose subcutaneous interferon beta-1a), and more patients on Lemtrada® were relapse-free at two years. In addition, in CARE-MS II, accumulation of disability was significantly slowed in patients given Lemtrada® vs. Rebif®. Further, patients treated with Lemtrada® were significantly more likely to experience improvement in disability scores than those treated with Rebif®, suggesting a reversal of disability in some patients. CARE-MS I and CARE-MS II Efficacy Results CARE-MS I and CARE-MS II (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis) are randomized Phase III studies comparing the investigational treatment alemtuzumab to a standard of care MS treatment, Rebif,in patients with relapsing-remitting MS who were naïve to prior treatment or who had relapsed while on prior therapy, respectively. The results from these trials for Lemtrada® were superior to Rebif® on clinical and imaging endpoints, including a reduction in relapse rate and are published in full in The Lancet. In both studies, Lemtrada® was significantly superior to Rebif® in reducing relapses. In CARE-MS I, 78 percent of patients treated with Lemtrada® remained relapse-free for two years, providing statistically significant improvement over Rebif® (77.6 percent vs. 58.7 percent, p<0.0001). In the CARE-MS II trial, 65 percent of patients treated with Lemtrada® were relapse-free at two years, compared to 47 percent with Rebif® (p<0.0001). In addition, in CARE-MS II, Lemtrada® reduced relapse rate to a greater extent than Rebif® in all subgroups defined by previous therapy, including: with or without any interferon therapy, and those previously treated with Rebif® or Copaxone® (glatiramer acetate injection). Study data also showed a strong clinical benefit by reducing the risk of sustained accumulation of disability in patients taking Lemtrada® in CARE-MS ll by 42 percent as compared with Rebif (p=0.008), with significant improvement in disability scores that suggested a reversal of pre-existing disability in some patients. In the trial, the mean disability score for patients treated with Lemtrada® decreased over a two-year period, indicating an improvement in their physical disability, while the mean score for patients given Rebif® increased, indicating a worsening of disability (p<0.0001). CARE-MS I and CARE-MS II Safety Results Safety results were consistent across both studies. The most common adverse events associated with Lemtrada® were infusion-associated reactions, most commonly headache, rash, pyrexia, nausea and urticaria. Infections were common in both groups. Infections more common on Lemtrada® treatment included nasopharyngitis, upper respiratory, urinary tract, herpes viral infections, sinusitis and influenza. Most infusion-associated reactions and infections were mild to moderate in severity and responded to standard treatments. In both CARE-MS I and CARE-MS II, the incidence of serious adverse events was similar between the two treatment arms. As previously reported, autoimmune disorders were more common on patients treated with Lemtrada®, primarily autoimmune thyroid disease. Approximately 1 percent of Lemtrada®-treated patients in each study developed immune thrombocytopenia (ITP) over the two year study period. There were no cases of anti-GBM disease reported during the study period with one case of glomerulonephritis during the follow-up period as has been previously reported. The percentage of Lemtrada®-treated patients reported to have malignant neoplasms was less than 1 percent. The overall safety profile was similar for the Lemtrada® 12 mg and 24 mg groups. In both trials, the autoimmune disorders were detected early through a monitoring program and managed using conventional therapies. Patient monitoring for autoimmune disorders is incorporated in all Genzyme-sponsored trials of Lemtrada® for the investigational treatment of multiple sclerosis
