FDA Approves Alemtuzumab for Relapsing Forms of Multiple Sclerosis

Genzyme announced the FDA has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis.

Genzyme announced the US Food and Drug Administration (FDA) has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS).

The company also noted that 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.”

Alemtuzumab is a monoclonal antibody that targets the CD52 protein, which is abundant in T and B cells. Treatment with alemtuzumab depletes circulating T and B lymphocytes after each treatment course.

The FDA approved alemtuzumab based on two randomized phase III studies that compared treatment with alemtuzumab to high-dose subcutaneous interferon beta-1a in patients with relapsing remitting MS who were either new to treatment (the CARE-MS I study) or who had relapsed while on prior therapy (CARE-MS II).

According to Genzyme, alemtuzumab was “significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance.” In the CARE-MS II study, alemtuzumab was “significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed” in patients given alemtuzumab vs. interferon beta-1a. The clinical development program for alemtuzumab involved “nearly 1,500 patients with more than 6,400 patient-years of safety follow-up.”

The FDA will require the alemtuzumab label to carry a boxed warning noting that treatment with alemtuzumab is associated with “a risk of serious, sometimes fatal autoimmune conditions, serious and life-threatening infusion reactions.” The label will also note that alemtuzumab “may cause an increased risk of malignancies including thyroid cancer, melanoma and lymphoproliferative disorders.”

Alemtuzumab can only be prescribed and dispensed through a restricted distribution, REMS (Risk Evaluation and Mitigation Strategy) program intended to help educate healthcare providers and patients on the serious risks associated with alemtuzumab and the appropriate periodic monitoring required to support the detection of these risks for 48 months after the last infusion.

Alemtuzumab “has a unique dosing and administration schedule of two annual treatment courses. The first treatment course is administered via intravenous infusion on five consecutive days, and the second course is administered on three consecutive days, 12 months later.”

During clinical trials, the most common side effects associated with alemtuzumab treatment were 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, and vomiting.

Other serious side effects include autoimmune thyroid disease, autoimmune cytopenias, infections and pneumonitis.