The European Medicines Agency (EMA) has published a new guideline on medicines for the treatment of lupus, its first on the topic.
Lupus erythematous (LE) is a chronic auto-immune inflammatory disease that manifests itself in either cutaneous (CLE) or systemic (SLE) form
In a statement released on 5 March 2013, EMA explained that while advancements in care have dramatically reduce mortalities and morbidities associated with the disease, "Many patients still have incompletely controlled disease and progress to end-stage organ failure."
"Therefore, there is a need for the development of effective medicines to treat this condition," the agency argued.
That's where EMA's new draft guideline, Clinical investigation of medicinal products for the treatment of systemic lupus erythematosus, cutaneous lupus and lupus nephritis, comes in, EMA explained. The document is intended to establish a framework covering the clinical investigation phase of products intended to treat SLE, including patient characteristics, inclusion and exclusion criteria and the use of other medicines during the trial.
For example, if sponsors wish to show evidence of a clear reduction in disease activity, they need to only enroll patients who exhibit "clinically important and sufficient level of disease activity prior to treatment," which should be measured at the enrolment phase to establish a baseline for treatment.
"In order to demonstrate prevention or reduction of flares (maintenance of clinical response) patients will need to have evidence of well documented flares for a period of 6-12 months prior to enrollment," EMA explained. These considerations may be more narrowly tailored depending on the type of lupus present in the patient, the agency added.
These patients should also be evaluated for any concomitant medications they may be taking, which regulators said should be "standardized and stable as far as possible without compromising optimization." This is meant to make sure that any changes observed are the result of the medication being studied, and not changes in existing therapies.
"Certain common practice modifications of background therapy could be allowed; these modifications should be well defined and carefully documented in the protocol (this includes also non-SLE medication, e.g. ACE inhibitors)," EMA wrote.
Evaluation of Safety and Efficacy
EMA also writes that it is looking to establish certain efficacy endpoints, though these are likely to vary depending upon the particular therapy in question and its mode of action. In general, however, endpoints might include "a reduction of disease activity, the prevention of flares/increased time intervals between flares and prevention of long-term damage."
All endpoints should be statistically and clinically relevant, and demonstrated "preferable through validated composite indexes in which the effect seen in an objective measure of reduction in global disease activity is not offset by worsening of the subject's condition overall or worsening in any specific organ system." Numerous indexes have already been validated for use by EMA, and are listed within the guideline.
Other secondary endpoints might also be relevant to regulatory evaluation, including the quality of a patient's life and reduced use of other medications (such as steroid dosing).
Biomarkers, too, were identified as being of potential use to clinical investigators, though EMA noted that none have yet been validated for use.
The drugs also need to undergo clinical safety evaluations, including monitoring for specific adverse events. As lupus patients are generally at greater risk for infections, malignancies and other cardiovascular complications due to the nature of the disease, EMA recommended that patients be especially monitored for the presence of these adverse events. Renal function and liver toxicities, too, should be watched especially closely as the organ may have already sustained damage from lupus.
Comments on the draft guideline are due by 4 September 2013.