Chapter 5 92 Table 1: Overview of all FDA and EMA approvals that rely in a pivotal way on real-world data from expanded access programs. Generic name Indication FDA3 EMA Studies4 N EA/N5 amphotericin B fungal infections 1997 N 10 CT (n=2,038), 1 EA (n=133) 0.06 (133/2,171) anagrelide essential thrombocythemia 1997 2004 2 SACT (n=35 + 254), 1EA (n=245) 0.45 (245/538) cholic acid inborn errors of bile acid metabolism 2015 2015 2 EA (n=63+22) 1.00 (85/85) clarithromycin Mycobacterium avium complex 1993 N6 1 RCT (n=154), 1 SACT (n=25), 1 EA (n=469) 0.72 (469/648) dinutuximab ꞵ neuroblastoma N7 2017 1 RCT (n=370), 1 SACT (n=44), 1 EA (n=54) 0.12 (54/468) fish oil triglycerides parenteral nutrition-associated cholestasis 2018 N 1 SACT (n=144), 1 EA (n=37) 0.20 (37/181) glucarpidase elevated methotrexate levels 2012 W 1 SACT (n=147), 1 EA (n=22) 0.13 (22/169) lutetium oxodotreotide neuroendocrine tumors 2018 2017 1 RCT (n=229), 1 EA (n=558) 0.71 (558/787) nitisinone tyrosinemias 2002 2005 1 EA (n=207) 1.00 (207/207) sodium phenylacetate/benzoate acute hyperammonemia in urea cycle disorders 2005 N 1 EA (n=316) 1.00 (316/316) uridine triacetate fluorouracil or capecitabine overdose 2015 N 2 EA (n=75+60) 1.00 (135/135) velmanase α alpha-mannosidosis N 2018 1 RCT (n=25), 1 EA (n=35) 0.58 (35/60) vestronidase α mucopolysaccharidosis VII 2017 2018 2 SACT (n=3+12), 1 EA (n=2)8 0.12 (2/17) 3 Year of EMA/FDA approval (if applicable). W: Withdrawn, N: Not approved. 4 Main studies that provided information on efficacy. SACT = single arm clinical trial, EA = expanded access, (R)CT = (randomized) controlled trial. 5 Ratio of patients in expanded access (nEa) to total number of patients in main studies (N) 6 Clarithromycin is approved in individual member states, before the introduction of the centralized procedure. 7 Dinutixumab α is marketed in the US (Unituxin) but not anymore in the EU (replaced by β). As α and β are not exactly equal, we opted not to compare α and β. 8 The EMA did not consider the 2 patients in EA for clinical efficacy.
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