Accelerated Approval and Oncology Drug Development Timelines
Authors: Michael L. Lanthier, Rajeshwari Sridhara, John R. Johnson, Ann Farrell, Patricia Keegan, Robert Justice, Richard Pazdur
Journal: Journal of Clinical Oncology (2010)

Richey et al 1 report that novel oncology drugs and biologics (new molecular entities [NMEs]) approved through the US Food and Drug Administration's accelerated approval (AA) pathway (21 CFR 314.510 [Subpart H] for new drug applications [NDAs], 21 CFR 601.41 [Subpart E] for biologics license applications [BLAs]) reach the market no faster than drugs that receive regular approval (RA).The authors state that the median development time from investigational new drug application (IND) to drug approval for AA oncology drugs was 7.3 years, whereas the median development time for RA oncology drugs was 7.2 years.They conclude that the AA program does not meet its intended purpose of bringing important new therapies to the market sooner.The authors acknowledge that they were unable to obtain 25% of the IND filing dates, which according their definitions were used to calculate drug development time. 1 In our experience, such a high level of missing data has the potential to substantively affect the outcome of the type of analysis conducted by Richey et al.Inaccuracies, which we identify regarding classification of approval status (AA or RA) and orphan drug designations, also may affect the outcome of such analyses and resultant conclusions.The authors state that tositumomab was approved under AA; however, this application received RA. 2 Although the authors classify bicalutimide as an RA, the approval letter clearly references AA. 2,3 The authors classify sunitinib as an AA and dasatinib as an RA.Sunitinib and dasatinib simultaneously received both AA and RA for different indications that were approved under separate NDA applications.The authors include cetuximab as an orphan drug approval; the original approval in February 2004 for treatment of epidermal growth factor receptor-expressing metastatic colorectal carcinoma did not receive an orphan drug designation.Two years later, in March 2006, cetuximab received a supplemental orphan approval for the treatment of head and neck cancer.The authors also failed to identify azacitidine as an orphan drug for the treatment of myelodysplastic syndromes. 4he authors incorrectly state that the gefitinib application for marketing approval was withdrawn by the sponsor; the drug remains available under restricted distribution provisions to patients who have previously received and are believed to be benefitting from treatment with gefitinib.After correcting the noted inaccuracies and including IND development times missing in the publication, we found that the median development times for NMEs for novel drugs and biologics receiving AA and RA were 6.1 years (range, 3.1 to 12.4 years) and 7.1 years (range, 3.0 to 33.4 years), respectively.If we count the approvals for sunitinib and dasatinib only once as the authors did, and accept their designations for these two drugs, similar results are observed (6.3 v 7.2 years, respectively).For nonbiologic NMEs approved through the NDA regulatory pathway (82% of the drugs in this data set, and 75% of the AAs), the difference between