The European Medicines Agency (EMA) has released a new general guidance document on the development of medicinal products intended to treat asthma, a condition that restricts a patient's airways and can be fatal if improperly treated.
Background and Overview
The document, Draft note for guidance on clinical investigation of medicinal products for treatment of asthma, is meant to provide general advice on the development of asthma products, including clinical development programs.
"The current revision has taken into account the updated international clinical recommendations for asthma, focused on a control-based management in order to include revised concepts of the disease and new variables developed to assess the effect of medicines for asthma treatment," wrote EMA. In addition, the guidance includes a "detailed chapter" on developing asthma medications intended for use in pediatric populations and some general considerations about developing immunotherapy-based treatments.
Among regulators' top concerns has to do with the nature of the disease and the length of treatment. Because asthma often develops at an early age, consumers may take a medication throughout their lives, greatly increasing the risk that they will be subject to adverse side effects, and making the long-term safety of the drug a particular concern to regulators. As a result, safety data in any trial conducted in support of an approval must be collected for a minimum for one year, with additional data asked of any new agents that work by suppressing immune function.
In the case of children, data should be provided for three distinct groups: Those under the age of six, those between the ages of six and 12, and those over 12 years of age. The guidance explains the unique enrollment, testing, endpoint and trial design criteria for each particular population.
EMA's guidance also notes a number of general clinical considerations, including the determination of eligibility of patients using pre-defined asthma diagnosis criteria, documenting a patients' history of particular allergens (in immunotherapy trials), profiling the inflammatory airway in cases where it is relevant to the drug's mechanism of action, and recording of a patient's physical attributes.
Different studies will be expected for each grade of asthma severity, EMA added.
In addition, a wide range of methods are available for sponsors who wish to assess the efficacy of an asthma treatment, including:
- lung function testing
- airway hyper-responsiveness and challenge testing
- asthma exacerbation testing
- symptom scores
- reliever use rates
- composite scores
- medication use reductions
- biomarkers of airway inflammation
- health-related quality of life
Studies should also employ comparators or concomitant treatments. EMA notes that a three-arm study is preferable in comparator studies, with a placebo treatment compared against an existing reliever medication and the investigational medication. Active comparator trials should be employed in trials where a drug is intended as a first-line controller treatment, again using a three-arm approach.
If a patient is engaged in existing therapy, it should be confirmed that the dosing is appropriate for the severity of their asthma before they are enrolled into a trial.
Consultation on the guidance ends on 31 December 2013. The document is a revision of an earlier guidance released in May 2003.
EMA: Draft note for guidance on clinical investigation of medicinal products for treatment of asthma