Expanded access as a source of real-world data: An overview of FDA and EMA approvals 93 5♦ Expanded Access as sole evidence Strikingly, the evidence from expanded access programs was the only evidence in four cases: (i) sodium phenylacetate and sodium benzoate (FDA), (ii) uridine triacetate (FDA), (iii) cholic acid (FDA/EMA) and (iv) nitisinone (FDA/EMA). We describe these approvals here in more detail. The combination of sodium phenylacetate and sodium benzoate (i) is indicated for the acute treatment of hyperammonemia in patients with urea cycle disorders, a rare disorder causing dangerously elevated ammonia levels. The observed treatment effect was considerable; historical control data showed a 48% survival rate, whereas 80% of the patients treated under expanded access with sodium phenylacetate and sodium benzoate survived.21 Uridine triacetate (ii) treats patients following 5-fluoruoacil or capecitabine overdose. Overdosing can lead to life threatening toxicities, uridine triacetate was therefore administered under emergency expanded access. Historical control data indicated that 16% of patients receiving only supportive care survived. In the expanded access program of uridine triacetate, survival rate was 97%.22 Cholic acid (iii) is approved for the life-long treatment of bile acid synthesis disorders. It replaces the abnormal bile acids produced by patients with inborn errors in primary bile acid synthesis. Effectiveness was established by comparing changes in bile acid levels before and after treatment. The submission package only included RWD from expanded access programs, because ‘the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence, and that it would be contrary to generally accepted principles of medical ethics to collect such information’.23 Nitisinone (iv) is a treatment for hereditary tyrosinemia type 1 (HT-1) and it prevents the flawed conversion of tyrosine. The expanded access program was coordinated from Sweden and patients were treated in 87 different hospitals in 25 countries. Marketing approval was granted 'in view of the rare occurrence and seriousness of the disease, the lack of therapeutic alternatives and the obvious clinical efficacy.'24
RkJQdWJsaXNoZXIy MTk4NDMw