Lemtrada (alemtuzumab) is a disease-modifying treatment to slow down the progression of relapsing-remitting multiple sclerosis (RRMS). Developed by Sanofi-Genzyme, it is used to lower the relapse rate and treat the symptoms of MS. Lemtrada is approved in more than 30 countries including the U.S., Canada, Scotland, Argentina, and the E.U.
Due to its safety profile, the U.S. Food and Drug Administration (FDA) recommends Lemtrada use be restricted to RRMS patients who have had an inadequate response to two or more MS therapies.
How Lemtrada works
MS is characterized by the abnormal proliferation of immune cells called T- and B-cells, which drive inflammation and the formation of brain lesions. Lemtrada is a humanized monoclonal antibody that binds to the so-called CD52 protein found on the surface of T- and B-cells, thereby inactivating them. Therefore, Lemtrada helps slow down the neuroinflammation in MS.
Although the way Lemtrada works has not been explored in depth, studies have shown that the level of expression of CD52 on immune cells correlates with the cell-killing effect of Lemtrada. Since B- and T-cells have high levels of CD52 on their surface, Lemtrada may have more effect on these cells compared with other cells.
Lemtrada in clinical trials
Two pivotal Phase 3 studies that compared the safety and efficacy of Lemtrada to Rebif (subcutaneous interferon beta 1a) in RRMS played a vital role in the approval of Lemtrada.
The first study (NCT00530348), called CARE-MS 1, included 581 RRMS patients, 18 to 50 years old, who were previously untreated. These patients were randomly grouped to receive 12 mg of Lemtrada or 44 mcg of Rebif. Lemtrada was intravenously given once per day for the first five days and then a year later, once per day for three days. Rebif was administered three days a week. The study lasted two years, and included 376 patients who received Lemtrada and 187 patients who were given Rebif.
Researchers found that 22 percent of the Lemtrada-treated patients relapsed compared with 40 percent of those treated with Rebif. Similarly, 78 percent in the Lemtrada group remained relapse-free for two years compared with 59 percent of those treated with Rebif. Despite the favorable results, severe side effects were reported in the Lemtrada-treated patients compared with the Rebif group.
The second two-year study (NCT00548405), called CARE-MS 2, included RRMS patients who had relapsed at least once despite treatment with Rebif. They were randomly assigned to receive 12 mg of Lemtrada, 24 mg of Lemtrada, or Rebif therapy. The results of this study were similar to those of the CARE-MS 1 study, showing Lemtrada treatment fairing significantly better than Rebif at preventing relapse. Similar side effects were reported in both studies.
Patients in the CARE-MS 1 study were given the option to participate in an extension study (NCT00930553) for up to five years during which they continued to receive treatment to manage MS relapse rates and symptoms. Researchers reported that Lemtrada treatment continued to provide long-term benefits to patients by preventing disease progression and reducing relapse rates. Of the 367 patients from the previous studies who chose to stay in the trial, 68.5 percent did not need any further treatment. Furthermore, about 60 percent of the patients showed no evidence of disease activity (NEDA) over three to five years.
The five-year extension study participants had the opportunity to further continue Lemtrada treatment (NCT02255656) for an additional evaluation period of five years. Researchers noted that 80 percent of the original CARE-MS 1 and 73 percent of the CARE-MS 2 participants had completed a seven-year follow-up. According to this trial, the benefits of Lemtrada treatment had been sustained: The majority of participants maintained their NEDA status and their brain volume loss was consistently low.
An ongoing study (NCT03774914) is assessing the risk of spontaneous abortions in women who were treated with Lemtrada for RRMS. A total of 204 women, from 18 to 55, who were or became pregnant between the first dose of treatment and four months after the last dose are eligible to participate in this study. The study is currently recruiting participants in Austria.
A Phase 4 study (NCT03135249) called SUPPRESS is evaluating sequential Lemtrada therapy after treatment with Tysabri (natalizumab), another approved treatment for RRMS. The study is recruiting about 40 patients in Texas, U.S., who are 18 to 60 years old and about to complete their Tysabri treatment. The course of MS will be followed closely during clinical visits with detailed medical history recorded to recognize signs of exacerbations. Brain MRIs will also help assess the impact of the treatment on brain volume loss.
Lemtrada is typically given intravenously twice annually, with the first infusion course administered over five consecutive days, and the second a year later for three consecutive days.
Common side effects of Lemtrada include rashes, joint pain, fungal infections, fatigue, urinary and upper respiratory tract infections, and nausea. Patients are advised to review their medical history, including vaccinations, with their doctor before starting the treatment.
Lemtrada can also cause serious side effects such as viral infections, infusion reactions, thyroid and skin cancer, and lymphoproliferative disorders. Therefore, it is only available through a restricted distribution program, the Lemtrada REMS (risk evaluation and mitigation strategy), to ensure that patients prescribed Lemtrada undergo periodic monitoring to detect potential health risks.
Since Lemtrada’s FDA approval in 2014, 13 cases of stroke and rupture of arteries in the head and neck caused by its use have been reported worldwide. Due to such life-threatening risks, the FDA issued its highest safety alert that a “boxed warning” be included in Lemtrada’s prescribing information on the label and the medication guide to inform patients of its significant and sometimes fatal risks.
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