The US Food and Drug Administration (FDA) on Thursday released a revised version of its draft guidance intended to help pharmaceutical companies develop products to treat the lung disease known as chronic obstructive pulmonary disease (COPD).
Specifically, FDA says the guidance is meant to assist sponsors in determining the efficacy of new drugs to treat the disease in Phase III clinical trials, and includes new information on using health-related quality-of-life instruments, such as St. George's Respiratory Questionnaire (SGRQ), as part of an endpoint assessment.
FDA says it developed its guidance to help address the "challenges and opportunities" in developing new molecular entities to treat COPD.
According to FDA, new drugs are needed to treat COPD, as it "is associated with significant morbidity and mortality, and current treatment options are limited." Today, most drugs used to treat COPD patients only address symptoms of the disease and have not been shown to address its cause or slow its progression.
However, FDA says that medical understanding of COPD has improved significantly in recent years, making it a good time to update its guidance on drug development for the disease.
When taking a novel approach not outlined in the draft guidance, FDA also encourages companies to seek advice from the agency or its Pulmonary-Allergy Drugs Advisory Committee.
FDA says that sponsors should specify whether a product is intended to treat the "whole spectrum of COPD patients or patients with only one of its clearly defined entities" early in the product development lifecycle.
"Because chronic bronchitis and emphysema are histologically and clinically distinct entities, we recognize that a drug may be effective for one and not the other," FDA writes.
FDA says it is currently aware of four approaches to treat COPD: drugs to "improve airflow obstruction, provide symptom relief, modify or prevent exacerbations, or alter the natural progression of the disease."
Due to the variety of approaches, FDA says sponsors should keep their products' mechanisms of action in mind when selecting endpoints and designing clinical trials.
When it comes to selecting an efficacy endpoint for a Phase III study, FDA says sponsors must choose an endpoint that's appropriate for a product's mechanism of action.
FDA breaks down the various types of endpoints into three groups: Objective physiological assessments, patient- or evaluator-reported outcome measures, and biomarkers and surrogate endpoints.
In the guidance, FDA makes specific recommendations to address the strengths and weaknesses of the different types of endpoints within the three groups.
For many of the types of endpoints, including exercise capacity, symptom scores, activity scales and health-related quality-of-life instruments, FDA cautions that such endpoints have limitations owing to their imprecise nature and may require additional validation.
For primary endpoints, FDA recommends sponsors consider the following primary endpoints:
- Change in force expiratory volume in one second (FEV1)
- Symptom relief
- Modifying or preventing exacerbations
- Altering disease progression
- Modifying lung structure
FDA says that secondary endpoints can add useful information about the effect of a drug.
"Use of subjective measures as important secondary assessments may be particularly useful in judging the value of mean changes in the primary endpoint. Similarly, in treatments intended to affect subjective perceptions of the disease through an effect on the underlying pathophysiology of COPD, secondary objective measures also can provide useful additional assessments to support the efficacy of the drug," FDA writes.