New Drug Review 2016

Jack DeRuiter, PhD; Pamela L. Holston, RPh, BS, BA; Taylor Joseph DeRuiter, PharmD


US Pharmacist. 2016;41(10):30-36. 

In This Article

Mepolizumab (Nucala, Glaxosmithkline)

Indication and Clinical Profile3,4

Mepolizumab has been approved for use as an add-on maintenance treatment for patients aged ≥12 years with severe eosinophilic asthma. Asthma is a chronic disease affecting more than 24 million people in the United States. It is characterized by periods of triggered exacerbations that cause airway inflammation, leading to difficulty in breathing and sometimes resulting in hospitalization.

FDA approval of mepolizumab was based on one dose-ranging trial and two confirmatory controlled trials in 1,327 patients. Study endpoints included frequency of exacerbations (trials 1 and 2), lung function as measured by volume of air exhaled in 1 second (all trials), and percentage of reduction of oral corticosteroid dose from baseline while maintaining asthma control (trial 3). Compared with placebo, patients receiving mepolizumab experienced significantly fewer exacerbations and were significantly more likely to reduce their daily maintenance oral corticosteroid dose by at least 50% while maintaining asthma control. However, mepolizumab treatment did not result in a significant improvement in lung function in any trial.

Pharmacology and Pharmacokinetics3,4

Mepolizumab is a humanized monoclonal antibody that binds to and inhibits interleukin-5 (IL-5), the primary cytokine responsible for eosinophil activation, recruitment, and differentiation. By inhibiting IL-5 signaling, mepolizumab effectively reduces the level of eosinophils in the blood, thereby limiting a key cellular component of the inflammatory process involved in asthma.

Mepolizumab is 80% bioavailable after SC injection, and its volume of distribution is estimated at 3.6 L. It is metabolized via proteolytic enzymes involved in endogenous protein catabolism throughout the body. Mepolizumab is cleared entirely metabolically at a rate of 0.28 L/day, and it has a mean terminal half-life of 16 to 22 days.

Adverse Reactions and Drug Interactions3,4

The most common adverse reactions reported in clinical trials of mepolizumab were headache, injection-site reactions, back pain, and fatigue. The use of mepolizumab was associated with an increased incidence of herpes zoster infection and possibly an increased risk of parasitic infections. As a monoclonal antibody, mepolizumab is associated with an increased risk of hypersensitivity reactions, and patients should be monitored after administration. Mepolizumab should not be used to treat acute bronchospasm or exacerbations, and patients receiving the drug should not have their oral or inhaled corticosteroid therapy reduced or discontinued abruptly. Data are insufficient regarding the safety of mepolizumab in pregnancy, but the drug may be transported across the placenta, and transport may increase as pregnancy progresses.

No formal drug-interaction studies involving mepolizumab have been performed, but the drug is not metabolized by CYP enzymes and it is not known to have any effect on CYP metabolism or P-glycoprotein pumps. Furthermore, there was no evidence of an effect of commonly coadministered drugs on mepolizumab exposure in population pharmacokinetic analyses during clinical trials.

Dosage and Administration3,4

Mepolizumab is supplied as 100-mg single-dose vials of lyophilized powder for reconstitution and SC injection by a healthcare professional. The recommended dosing is 100 mg by SC injection into the upper arm, thigh, or abdomen once every 4 weeks. The safety and efficacy of mepolizumab in patients aged <12 years have not been established. Although there are no trial data on patients with hepatic or renal impairment, no dose adjustments are specifically required, as it is unlikely that reduced hepatic or renal function would substantially affect the clearance rate of mepolizumab.