LEMTRADA

What it is

Lemtrada is a recombinant DNA-derived humanised monoclonal antibody directed against the 21–28 kD cell surface glycoprotein, CD52. Each 1.0 mL of concentrate solution contains 10 mg alemtuzumab. Lemtrada is a sterile, clear, colourless to slightly yellow, injection concentrate with pH 7.0–7.4, intended for dilution prior to infusion.

Approved indications

— Lemtrada is indicated for the treatment of relapsing forms of multiple sclerosis for patients with active disease defined by clinical or imaging features to slow the accumulation of physical disability and reduce the frequency of clinical relapses.

Dosing overview

The recommended dose of Lemtrada is 12 mg/day administered by IV infusion for 2 or more treatment courses. The initial treatment consists of a first course of 12 mg/day on 5 consecutive days (60 mg total dose) and a second course of 12 mg/day on 3 consecutive days (36 mg total dose) administered 12 months after the first course. Additional treatment with a third or fourth course comprises 12 mg/day on 3 consecutive days (36 mg total dose) administered at least 12 months after the prior treatment course. Lemtrada should be administered by IV infusion over a period of approximately 4 hours.

Key safety warnings

Treatment with Lemtrada may result in the formation of autoantibodies and increase the risk of autoimmune mediated conditions which may be serious and life threatening. Reported autoimmune conditions include thyroid disorders, immune thrombocytopenic purpura (ITP), or uncommonly, vasculitis, nephropathies, autoimmune hepatitis, acquired haemophilia A, thrombotic thrombocytopenic purpura, and autoimmune encephalitis. Endocrine disorders including autoimmune thyroid disorders have been observed in an estimated 36.8% of patients treated with alemtuzumab, with observed autoimmune thyroid disorders including hyperthyroidism or hypothyroidism. Most events were mild to moderate in severity, although serious endocrine events occurred in 4.4% of patients. Serious events of ITP have been observed in 12 patients treated with alemtuzumab in controlled clinical trials in MS, with an annualised rate of 0.0047 events/patient/year. In a controlled clinical trial, one patient developed ITP that went unrecognised prior to monthly blood monitoring requirements and died from intracerebral haemorrhage. An additional 12 serious events of ITP have been observed through up to 12 years follow-up. ITP onset has generally occurred between 14 and 36 months after first alemtuzumab exposure. Infections occurred in 71% of patients treated with alemtuzumab compared to 53% of patients treated with Rebif in controlled clinical trials. Infections that occurred more often in alemtuzumab-treated patients included nasopharyngitis, urinary tract infection, upper respiratory tract infection, sinusitis, oral herpes, influenza, and bronchitis. Serious infections occurred in 2.7% of patients treated with alemtuzumab as compared to 1.0% of patients treated with interferon beta-1a. In the postmarketing setting, serious and life-threatening stroke (including ischaemic and haemorrhagic stroke) has been reported within one week of Lemtrada administration, with most cases occurring within 3 days. Cervicocephalic arterial dissections involving multiple arteries were reported in some cases.

Contraindications

Lemtrada is contraindicated in patients with hypersensitivity or anaphylactic reactions to alemtuzumab, to murine proteins or to any of the excipients, and in patients with human immunodeficiency virus infection. Lemtrada is also contraindicated in patients with severe active infection, uncontrolled hypertension, a history of arterial dissection of the cervicocephalic arteries, a history of stroke, a history of angina pectoris or myocardial infarction, and in patients with known coagulopathy or on concomitant anticoagulant therapy.

PBS listing

Lemtrada solution concentrate for intravenous infusion 12 mg in 1.2 mL is listed on the PBS with streamlined restriction and an ex-manufacturer price of A$10283.09.

Regulatory history

Lemtrada alemtuzumab 10 mg/mL injection concentrate was first listed on the ARTG on 18 December 2013. Lemtrada was approved by the TGA on 11 December 2013, receiving initial registration on the ARTG on 18 December 2013.