General Information

Lemtrada (alemtuzumab) is a monoclonal antibody that targets CD52, a protein abundant on T and B cells. Circulating T and B cells are thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab depletes circulating T and B lymphocytes after each treatment course. Lymphocyte counts then increase over time with a reconstitution of the lymphocyte population that varies for the different lymphocyte subtypes.

Lemtrada is specifically indicated for the treatment of patients with relapsing forms of multiple sclerosis, to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, the use of Lemtrada should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

Lemtrada is supplied as a solution for intravenous infusion. 

• The recommended dosage of Lemtrada is 12 mg/day administered by intravenous infusion for 2 treatment courses: First Treatment Course: 12 mg/day on 5 consecutive days (60 mg total dose).
• Second Treatment Course: 12 mg/day on 3 consecutive days (36 mg total dose) administered 12 months after the first treatment course.

Following the second treatment course, subsequent treatment courses of 12 mg per day on 3 consecutive days (36 mg total dose) may be administered, as needed, at least 12 months after the last dose of any prior treatment courses.

Mechanism of Action

Lemtrada (alemtuzumab) is a monoclonal antibody that targets CD52, a protein abundant on T and B cells. Circulating T and B cells are thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab depletes circulating T and B lymphocytes after each treatment course. Lymphocyte counts then increase over time with a reconstitution of the lymphocyte population that varies for the different lymphocyte subtypes.

Side Effects

Adverse effects associated with the use of Lemtrada may include, but are not limited to, the following:

• rash
• headache
• pyrexia
• nasopharyngitis
• nausea
• urinary tract infection
• fatigue
• insomnia
• upper respiratory tract infection
• herpes viral infection
• urticaria
• pruritus
• thyroid gland disorders
• fungal infection
• arthralgia
• pain in extremity
• back pain
• diarrhea
• sinusitis
• oropharyngeal pain
• paresthesia
• dizziness
• abdominal pain
• flushing
• vomiting
• Serious side effects including autoimmune thyroid disease, autoimmune cytopenias, infections and pneumonitis.

The Lemtrada label includes a boxed warning noting a risk of serious, sometimes fatal autoimmune conditions, serious and life-threatening infusion reactions and also noting Lemtrada may cause an increased risk of malignancies including thyroid cancer, melanoma and lymphoproliferative disorders. Lemtrada is only available through a restricted distribution program, the Lemtrada REMS (Risk Evaluation and Mitigation Strategy).

Clinical Trial Results

The FDA approval of Lemtrada was based on two phase III randomized, open-label,blinded studies comparing treatment with Lemtrada to Rebif (high-dose subcutaneous interferon beta-1a) in patients with relapsing remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II).

CARE-MS 1

This trial enrolled 581 subjects who had not received treatment. The trial compared alemtuzumab to Rebif according to two co-primary endpoints: the time to sustained accumulation of disability and the annualized relapse rate. Alemtuzumab was dosed at 12 mg/day for five days by daily IV infusion, with a second dosing 12 months later of 12 mg/day for three days. Rebif was administered three times per week. Lemtrada was significantly more effective than Rebif at reducing annualized relapse rate (0.18 for Lemtrada and 0.39 for interferon beta-1a (p<0.0001) a 55 percent relative reduction. The difference observed in proportion of patients with disability progression at year two did not reach statistical significance (8% for Lemtrada and 11% for Rebif (p=0.22)), a relative risk reduction of 30 percent. The percent of patients remaining relapse-free at year two for Lemtrada was 78% vs. 59% for Rebif (p<0.0001). The percent change in T2 lesion volume from baseline did not reach statistical significance (-9.3 for Lemtrada and -6.5 for Rebif, p=0.31).

CARE-MS II

This trial enrolled 840 subjects who had relapsed on prior therapy. The subjects received alemtuzumab intravenous 12 mg per day for 5 consecutive days, and again for three days one year later, or treatment with Rebif 44 mcg administered by injection three times per week throughout the two years of study. Lemtrada was significantly more effective than Rebif at reducing annualized relapse rates (0.26 for Lemtrada and 0.52 for interferon beta 1-a, p<0.0001, a 49 percent relative reduction). The proportion of patients with confirmed six-month disability progression was significantly lower for Lemtrada (13% for Lemtrada vs. 21% for Rebif, p=0.0084), a 42 percent relative risk reduction. The percent of patients remaining relapse-free at year two for Lemtrada was 65% vs. 47% for Rebif (p<0.0001). The percent change in T2 lesion volume from baseline did not reach statistical significance (-1.3 for Lemtrada and -1.2 for Rebif, p=0.14).