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FDA Advisers Recommend Approval of Asthma Drug Reslizumab for Adults

Approval decision expected by March 2016

The FDA’s Pulmonary–Allergy Drugs Advisory Committee (PADAC) has recommended that the agency approve the investigational drug reslizumab (Cinqair, Teva Pharmaceutical Industries) for the treatment of severe asthma in patients 18 years of age and older.

The panel voted unanimously that the drug should not be approved for children aged 12 to 17 years.

The FDA is not required to follow the advice of its expert advisory panels, but it usually does so.

Reslizumab is a humanized monoclonal antibody (IgG4 kappa) that binds to human interleukin 5 (IL-5). While several cytokines can affect eosinophils, IL-5 is the main cytokine involved in the regulation of blood and tissue eosinophils.

Reslizumab for injection is not currently marketed in the U.S. or in any other country in the world. However, another monoclonal antibody-targeting IL-5, mepolizumab (Nucala, GlaxoSmithKline), was approved in the U.S. in November 2015. Mepolizumab is indicated for add-on maintenance treatment in patients aged 12 years and older with severe asthma and with an eosinophilic phenotype. While the reslizumab program has also studied asthma patients with an eosinophilic phenotype, the proposed indication includes patients of a lesser disease severity (uncontrolled on inhaled corticosteroids). The basis for the approval of mepolizumab was a reduction in asthma exacerbations, oral corticosteroid-sparing activity, and a positive trend toward improvement in asthma symptoms. If approved, reslizumab would be another choice in the class of anti–IL-5 agents.

Teva submitted five principal efficacy and safety studies in support of the proposed asthma indication. These studies included a 16-week dose-ranging lung-function trial (Study 3081) and two 52-week exacerbation trials (Studies 3082 and 3083). These studies were conducted in patients 12 years of age and older with moderate-to-severe asthma and baseline blood eosinophil counts greater than or equal to 400/mcL. A fourth trial (Study 3084) was a 16-week lung-function study in patients unselected for baseline eosinophil levels; it was designed to support Teva’s definition of their chosen eosinophil threshold by examining the forced expiratory volume in 1 second (FEV1) response and blood eosinophil count interaction.

According to a briefing document supplied to the advisory panel, the efficacy of reslizumab in severe asthma was supported by data from the exacerbation and lung-function studies, but interpretation of these findings was limited by the lack of sufficient dose-ranging data. Study 3081 observed a mean 286-mL increase in FEV1 for reslizumab 3.0 mg/kg IV compared with a mean 127-mL increase for placebo over 16 weeks (treatment difference of 0.16 L; P = 0.002). Study 3082 observed an exacerbation rate of 0.9 per year for reslizumab compared with 1.8 per year for placebo (a 50% reduction) over 52 weeks (P < 0.0001). Similarly, Study 3083 observed an exacerbation rate of 0.86 per year for reslizumab compared with 2.11 per year for placebo over 52 weeks (P < 0.0001). A paradoxical increase in asthma exacerbation rates was observed in adolescent, African-American, and U.S. patients, although the evidence for improvement in lung function generally was supportive.

The FDA is slated to decide by March 2016 whether to approve reslizumab for its requested indication.

Sources: Reuters; December 9, 2015; and FDA Briefing Document; December 9, 2015.

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