Regulatory and scientific issues regarding use of foreign data in support of new orphan drug applications for approval by the FDA
The globalization of clinical research is demonstrated by the exponential increase in clinical trials conducted outside of the United States. These have been submitted to the US Food and Drug Administration (FDA) for marketing approval of new drug applications. An interesting article published in Nature written by FDA employees, discuss their experience with submissions of results from clinical trials performed outside the US in specific therapeutic areas, including orphan drugs. They also discuss the “extent of this practice, differences between the effectiveness and safety outcomes of studies conducted inside and outside the United States, and the FDA’s approach to acceptance of these trials”.
According to the authors, in the area of orphan drugs, the FDA exercises “greater regulatory flexibility” due to the rarity of the diseases in question and the difficulty of finding adequate number of patients to perform an efficient clinical trial, thus making FDA approval for orphan drugs based entirely on foreign data more likely. The authors provide a several examples where the FDA has approved drugs based completely on data gathered from countries other than US. These examples include the approval of velaglucerase alfa for type 1 Gaucher disease for which the clinical trials were conducted in five countries - Argentina, Paraguay, Israel, Russia, and Tunisia. The FDA has also approved carglumic acid for the treatment of hyperammonemia in patients with N-acetyl-glutamate synthase deficiency of the urea cycle was also based on data from from France, Germany, and the United Kingdom. Thus, the authors confirm the FDA’s eagerness on the use of cross border data from clinical trials for orphan drugs.
Consult the PubMed abstract
Mucopolysaccharidosis type I (MPS I) is a genetic disease caused by the deficiency of -L-iduronidase (IDUA) activity. MPS I is classified into three clinical phenotypes called Hurler, Scheie, and Hurler-Scheie syndromes according to their clinical severity. Although treatments for MPS I are available, better outcomes are associated with early treatment, which suggests a need for newborn screening for MPS I. An article published in Orphanet Journal of Rare Diseases was to determine whether measuring IDUA activity in dried blood on filter paper was effective in newborn screening for MPS I. The authors conducted a newborn screening pilot program for MPS I from October 01, 2008 to April 30, 2013. This screening involved measuring IDUA activity in dried blood spots from 35,285 newborns using a fluorometric assay. The authors observed that of the 35,285 newborns screened, 19 did not pass the tests and were recalled for examination, out of which three were recalled for leukocyte IDUA enzyme activity testing. The authors reported that two of the three had deficient leukocyte IDUA activity, while DNA analyses confirmed the diagnosis of MPS I in these two newborns. Thus from this study, the authors conclude that it is feasible to use the IDUA enzyme assay for newborn screening. The authors report that the incidence of MPS I in Taiwan estimated from this study is about 1/17,643. 
