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MS Treatment Alemtuzumab (Lemtrada) Gets FDA Green Light

Approval based on data from two pivotal studies

The FDA has approved alemtuzumab (Lemtrada, Genzyme/Sanofi) for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of alemtuzumab should generally be reserved for patients who have shown an inadequate response to two or more drugs indicated for the treatment of MS.

The FDA’s approval of alemtuzumab was based on data from two pivotal, randomized, phase III, open-label, rater-blinded studies that compared alemtuzumab with high-dose subcutaneous interferon (IFN) beta-1a (Rebif, EMD Serono/Pfizer) in patients with relapsing/remitting MS who were either new to treatment (CARE-MS I) or had relapsed while receiving prior therapy (CARE-MS II).

In the CARE-MS I trial, alemtuzumab was significantly more effective than IFN beta-1a at reducing the annualized relapse rate (0.18 for alemtuzumab vs. 0.39 for IFN beta-1a; P < 0.0001 –– a 55% relative reduction). The difference observed in the proportion of patients with disability progression at year 2 did not reach statistical significance (8% for alemtuzumab vs. 11% for IFN beta-1a; P = 0.22 –– a relative risk reduction of 30%). The proportion of patients remaining relapse-free at year 2 for alemtuzumab was 78% compared with 59% of patients receiving IFN beta-1a (P < 0.0001). The percent change in T2 lesion volume from baseline did not reach statistical significance (–9.3 for alemtuzumab vs. –6.5 for IFN beta-1a; P = 0.31).

In the CARE-MS II trial, alemtuzumab was significantly more effective than IFN beta-1a at reducing annualized relapse rates (0.26 for alemtuzumab vs. 0.52 for IFN beta-1a; P < 0.0001 –– a 49% relative reduction). The proportion of patients with confirmed 6-month disability progression was significantly lower for alemtuzumab than for IFN beta-1a (13% vs. 21%, respectively; P = 0.0084 –– a 42% relative risk reduction). The proportions of patients remaining relapse-free at year 2 were 65% for alemtuzumab compared with 47% for IFN beta-1a (P < 0.0001). The percent change in T2 lesion volume from baseline did not reach statistical significance (–1.3 for alemtuzumab vs. –1.2 for IFN beta-1a; P = 0.14).

The labeling for Lemtrada (alemtuzumab) includes a boxed warning noting a risk of serious, sometimes fatal autoimmune conditions and a risk of serious and life-threatening infusion reactions. The label also notes that Lemtrada may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders.

Lemtrada is available only through a restricted distribution program, the Lemtrada Risk Evaluation and Mitigation Strategy (REMS). This program was developed to ensure that access to Lemtrada in the U.S. is only through certified prescribers, health care facilities, and specialty pharmacies and to ensure that patients are enrolled in the REMS program. The program is intended to help educate health care providers and patients about the serious risks associated with Lemtrada and the appropriate periodic monitoring required to support the detection of these risks for 48 months after the last infusion.

The administration of Lemtrada involves two annual treatment courses. The first course is administered via intravenous infusion on five consecutive days, and the second course is given on three consecutive days 12 months later.

Alemtuzumab is a monoclonal antibody that targets CD52, a protein 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, which varies for the different lymphocyte subtypes.

The most common adverse effects of treatment with alemtuzumab have included 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 an extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. Serious side effects associated with alemtuzumab include autoimmune thyroid disease, autoimmune cytopenias, infections, and pneumonitis.

Approximately 400,000 Americans have MS.

Source: Genzyme Corporation; November 14, 2014.

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