Lemtrada (alemtuzumab) is a disease-modifying treatment by Sanofi Genzyme for active relapsing-remitting multiple sclerosis (RRMS).1 It was approved by the European Medicine Agency (EMA) in September 2013 and by the US Food and Drug Administration (FDA) in November 2014.2,3
It is an intravenous infusion given at a dose of 12 mg per day for 5 consecutive days at month 0 and daily for 3 consecutive days at month 12.4
It is only available through the Lemtrada risk evaluation and mitigation strategy (REMS) program and is only given to patients with active relapsing muscular sclerosis (MS) who showed an inadequate response to 2 or more disease-modifying treatments.1,4
Mechanism of Action
Lemtrada is a humanized anti-CD52 monoclonal antibody that recognizes CD52 on lymphocytes. It leads to the lysis of T and B lymphocytes, NK cells, monocytes, and macrophages.3,4 It is thought that the depletion of proinflammatory leukocytes and gradual reconstitution of immunity leads to an alteration in lymphocyte profile, reducing the immune system’s damaging activity in MS.
Warnings, Precautions, and Adverse Reactions
Lemtrada treatment can cause serious side effects, including autoimmune problems such as immune thrombocytopenic purpura and anti‑glomerular basement membrane disease.1 It can also cause serious infusion reactions that could be lethal. Other serious side effects include stroke, tears in the carotid and vertebral arteries, and certain cancers.
Lemtrada use can also cause hypothyroidism, hyperthyroidism, cytopenias, hemophagocytic lymphohistiocytosis, acquired hemophilia A, serious infections including progressive multifocal leukoencephalopathy (PML), acalculous cholecystitis, and pneumonitis.
Get detailed prescribing information on the Lemtrada monograph page on MPR.
The most common side effects of Lemtrada are rash, headaches, thyroid problems, fever, swelling in the nose and throat, nausea, vomiting, diarrhea, urinary tract infection, fatigue, insomnia, upper respiratory infection, hives, itching, herpes and fungal infections, joint, back, mouth, stomach, and arm and leg pain, sinus infections, tingling, dizziness, and sudden redness in the face, neck, or chest.
Lemtrada may be toxic to the fetus, and therefore, pregnant women should not be treated with Lemtrada.4 Women of reproductive age who receive Lemtrada treatment should use an effective method of contraception and continue to do so for at least 4 months following treatment. It is not known whether Lemtrada passes to breast milk so women who received Lemtrada treatment are advised not to breastfeed within 4 months of treatment.
Patients should complete their necessary immunizations at least 6 weeks before starting Lemtrada treatment and those treated with Lemtrada should not be given live vaccines.4
Efficacy in Clinical Trials
The approval of Lemtrada was based on the results of 2 pivotal clinical trials involving 1421 patients with RRMS, called CARE-MS I and CARE-MS II.
CARE-MS I was a phase 3 randomized, rater-blinded study comparing the effects of 2 annual cycles of Lemtrada to that of Rebif treatment in patients with RRMS.5 The primary outcome measures were the percentage of participants with a sustained accumulation of disability and the annualized relapse rates. Secondary outcome measures were the percentage of participants who were relapse-free, changes at 2 years compared to the baseline in expanded disability status scale (EDSS) scores, MS functional composite score, and MRI-T2 hyperintense lesion volume.
The trial enrolled patients with RRMS aged 18 to 50 years who had received no previous treatments. Results showed that the average number of relapses per year in patients treated with Lemtrada was less than half that of those treated with Rebif®.6 However, there was no meaningful effect in terms of disability progression between the 2 groups of patients.
CARE-MS II aimed to assess the safety and efficacy of 2 different doses (12 mg and 24 mg) of Lemtrada compared to Rebif.7 It recruited patients with RRMS aged 18 to 55 years who had at least 1 relapse while being treated with interferon beta or glatiramer acetate.
The results of this study also showed that the average number of relapses per year in patients treated with Lemtrada was reduced compared to patients treated with Rebif.3
Patients who participated in CARE-MS I and CARE-MS II were given the opportunity to participate in an open-label, rater-blinded extension study to assess the long-term safety and efficacy of Lemtrada.8 During the extension study, participants were given up to 2 additional doses of Lemtrada at 1-year intervals in case of disease progression.
The results showed that more than half of the patients included in the study had no disease progression and so were not given Lemtrada. In patients who needed additional Lemtrada treatment, the number of relapses was lower and disability progression was slower compared to the previous year.3
1. Lemtrada (alemtuzumab). Genzyme. Accessed June 14, 2021.
2. Lemtrada FDA approval history. Drugs.com. Accessed June 14, 2021.
3. Lemtrada. European Medicines Agency. Accessed June 14, 2021.
4. Lemtrada (alemtuzumab). Cleveland Clinic. Accessed June 14, 2021.
5. Comparison of alemtuzumab and Rebif® efficacy in multiple sclerosis, study one (CARE-MS I). ClinicalTrials.gov. September 17, 2007. Updated November 24, 2014. Accessed June 14, 2021.
6. Cohen J, Coles A, Arnold D, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819-1828. doi:10.1016/S0140-6736(12)61769-3
7. Comparison of alemtuzumab and Rebif® efficacy in multiple sclerosis, study two (CARE-MS II). ClinicalTrials.gov. September 17, 2007. Updated November 24, 2014. Accessed June 14, 2021.
8. An extension protocol for multiple sclerosis patients who participated in Genzyme-sponsored studies of alemtuzumab. ClinicalTrials.gov. June 30, 2009. Updated May 15, 2017. Accessed June 14, 2021.
Reviewed by Kyle Habet, MD, on 7/1/2021.