FDA-Approved Medications: New Data on Previously Approved Medications
- Intravenous infusion over four hours for two treatment courses:
First course: 12 mg/day on five consecutive days;
Second course: 12 mg/day on three consecutive days 12 months after the first treatment course
- Approved for RMS in 2014
Lemtrada® (alemtuzumab) is a monoclonal antibody. Its exact mechanism of action is unknown, but it is believed to involve binding to a cell surface antigen found on key immune-system cells, including T and B lymphocytes, leading to the depletion of these cells and other effects on the inflammatory process. Because Lemtrada can cause serious autoimmune conditions and infusion reactions, and can increase the risk for some cancers, its use is typically reserved for individuals who have not responded adequately to two or more other diseasemodifying therapies.
Lemtrada was approved for use in RMS on the basis of the Phase III CARE MS I and CARE MS II trials; both studies compared the medication with subcutaneous interferon beta-1a over two years of treatment. Now, new data indicate that Lemtrada’s effects on slowing MS disease progression are maintained with long-term use.
A total of 290 individuals with RMS who completed two courses of Lemtrada in the CARE-MS I trial entered a four-year extension study. They then were evaluated for an additional two years as part of a second extension study, called TOPAZ. In all, patients were evaluated for eight years after they started Lemtrada. During both the initial CARE-MS I extension study and TOPAZ, participants could receive additional courses of Lemtrada or another disease-modifying therapy at the investigators’ discretion, but more than half (56 percent) received no additional treatment during TOPAZ.
At the eight-year evaluation mark, the annualized relapse rate was 0.14, and 88 percent of the participants were relapse-free. Expanded Disability Status Scale (EDSS) scores were stable or improved from the core baseline for 78 percent of patients; 71 percent were free of six-month confirmed disability worsening; 41 percent achieved sixmonth confirmed disability improvement; and 60 percent had no evidence of disease activity. In addition, 87 percent had no new T1-enhancing lesions, and 67 percent had no new or enlarging T2-hyperintense lesions.13
Similarly, people with RMS who received interferon beta-1a therapy during the core CARE-MS II trial and who then were switched to Lemtrada for the CARE-MS II extension period and TOPAZ, showed significant improvements six years after switching to Lemtrada. The annualized relapse rate for the 117 individuals in this group was 0.19, and EDSS scores were stable or improved from CARE-MS II baseline in 68 percent of the participants. Similar to the CARE MS I findings, reductions in evidence of disease activity on MRI, as measured by assessment of T1-enhancing lesions, and new or enlarging T2-hyperintense lesions, were reported.39
CARE-MS I researchers also found that Lemtrada reduced levels of serum neurofilament light chain (sNfL), a biomarker of neuro-axonal damage in MS that can measure response to a disease-modifying therapy. Researchers analyzed more than 1,500 sNfL samples from 329 patients who had active MS at baseline and who then were treated with Lemtrada. Median sNfL levels fell significantly, from 31.6 pg/mL at baseline to 17.2 pg/mL six months after Lemtrada treatment, and between 13.0 and 13.9 pg/mL two years after therapy. During the same period, MRI disease activity and brain volume loss also decreased in these patients. The researchers plan to analyze more than 7,000 sNfL samples across seven years to obtain a more-detailed picture of how sNfL reduction may slow MS disease progression.40
In another trial, researchers in the United Kingdom and Ireland found positive results in individuals with RMS who switched from Tysabri® (natalizumab) to Lemtrada. Of the 79 participants in the trial, 51 were followed for more than two years after initial Lemtrada infusions, and independent blinded MRI analysis was performed in 20 patients. Data were analyzed in five phases: pre-Tysabri treatment, Tysabri treatment, the medication switch period, Lemtrada treatment, and post-Lemtrada treatment.
Mean annualized relapse rates fell from 2.3 before Tysabri treatment to: 0.8 during Tysabri treatment; 0.4 during Lemtrada treatment; and 0.5 after the last Lemtrada treatment.41