Introduction to the Canadian Scientific Advisory Committee on Respiratory and Allergy Therapies: In Vivo Evaluation For Clinical Testing in COPD and Asthma Therapy Using Generics

Abstract

Abstract

Background:

Health Canada posted a guidance for in vivo testing of subsequent market entry (SME) inhaled corticosteroids (ICS) for treatment of asthma and published proceedings regarding SME products for chronic obstructive pulmonary disease (COPD). This manuscript reviews these recommendations and outlines their rationale.

Methods:

The Scientific Advisory Committee on Respiratory and Allergy Therapies (SAC-RAT) met between 2007 and 2009. The committee reviewed approval processes for SME ICS for asthma treatment and a draft guidance was posted by Health Canada. SAC-RAT also reviewed SME long-acting beta agonists (LABA) and fixed drug dose combinations (FDDC) for COPD treatment.

Results:

SAC-RAT concluded that measuring airway eosinophils in mild, stable, steroid-naive, subjects was reproducible and measurable. Study duration could be reduced to only 3 weeks using this inflammatory outcome to establish therapeutic equivalence between SME ICS and Canadian reference product. A placebo limb of the trial was added to establish biological activity of the products. The committee recommended that LABA SME products be tested in a clinically stable, representative population with GOLD stage 2 and/or 3 COPD. There was not agreement regarding the extent of allowed FEV₁ reversibility in this population. The FEV₁ area under the curve (AUC) was recommended as a primary endpoint. For equivalence, both AUC and the shape of the curve (assessed by the peak and trough) over a 12-h period should be different from placebo but similar for the SME and reference products. Secondary endpoints were not recommended.

Conclusions:

Clinical presentations of asthma and COPD may overlap but prespecified disease phenotypes can separate the populations. ICS therapeutic equivalence can be assessed by reduction in eosinophil counts tested in steroid naive subjects. Increases in FEV₁ define LABA effects in moderate to severe COPD. When designing trials to assess therapeutic equivalence, the anticipated mechanism of action of the drug should be used to determine outcome measures.