The European Medicines Agency (EMA) on Monday adopted revised versions of its drug development guidelines for two inflammatory bowel diseases, Crohn's disease and ulcerative colitis.
The guidelines are intended to facilitate drug development in the specific disease areas by providing tailored recommendations to drugmakers for the clinical development of new products to treat the respective conditions.
Last updated in 2016, the 19-page guideline provides recommendations for the clinical development of drugs to treat Crohn's disease, including patient enrollment, endpoint selection, study design, safety considerations and risk management plans.
For its second revision, EMA says the guideline has been updated with changes to the recommendations for study design for adult patients with regard to treatment claims, primary and secondary endpoints and comparators to use in the studies.
According to EMA, sponsors should no longer use combined indexes, such as the Crohn's Disease Activity Index (CDAI), as the primary endpoint for their studies. Instead, the agency says sponsors should evaluate symptoms and inflammation separately as co-primary endpoints.
As for comparators, EMA says it is necessary to have a direct comparison against a standard first line treatment. EMA also says that having a placebo arm is ideal unless the study aims to show superiority against a standard of care comparator.
For sponsors looking to get a second-line therapy indication, EMA says that a placebo is an acceptable comparator, though in certain populations an active comparator may be necessary as well.
The guideline also includes additional clarification on whether data from adult patients can be extrapolated to children, or whether separate pediatric studies are necessary, and gives specific recommendations on evaluating pharmacokinetic and pharmacodynamic (PD/PD) data for pediatric development.
In its first revision to its 2008 guideline on developing new products to treat ulcerative colitis, EMA has updated the 18-page guideline with new recommendations for study design, endpoint selection and possible comparators.
As for primary endpoints, EMA says that sponsors should measure both the proportion of patients with symptomatic remission based on patient reported outcomes and the proportion of patients with endoscopic remission.
EMA also lays out similar criteria for comparators as in the Crohn's disease guideline, noting that a direct comparison with a generally accepted standard first line treatment is necessary for first line indications, while a placebo is acceptable for second line indications.
As with the Crohn's disease guideline, EMA has also added recommendations for pediatric extrapolation and considerations for pediatric PK/PD.
, Ulcerative Colitis