Table 1.

Selected regulatory failures since 2005

AgentsTargetIndicationLessons learnedReference
Bevacizumab (Avastin; Roche/Genentech)VEGFRBreast cancerODAC recommended and FDA withdrew approval on November 18, 2011.(36, 50)
Dutasteride (Avodart; GlaxoSmithKline)5α reductaseProstate cancer risk reductionFDA rejected sNDA, January 2011(51, 52)
Finasteride (Proscar; Merck)Type II 5α reductaseProstate cancer risk reductionFDA rejected sNDA, January 2011(53, 54)
Trastuzumab emtansine (T-DM1; Roche/Genentech)HER2Breast cancerAccelerated approval denied, FDA awaits phase III data, August 2010(47)
Gemtuzumab ozogamicin (Mylotarg; Pfizer)CD33AMLVoluntarily withdrawn from U.S. markets, June 21, 2010(48, 55)
Omacetaxine mepesuccinate or homoharringtonine (Omapro; ChemGenex)BcrAbl T315I mutationCMLODAC recommended development of companion diagnostic test for the BcrAbl T351I mutation prior to approval, April 10, 2010(56, 57)
Pixantrone Pixantrone, BBR 2778 (Pixuvri; Cell Therapeutics)Topoisomerase IIRelapsed or refractory NHLAccelerated approval denied, April 2010(58)
Single-arm trial, accrual only 44% of planned enrollment
Laromustine (Onrigin; Vion)AMLODAC recommended and FDA required a randomized study, SPA rejected, September 2009(59–61)
Trabectidin, ET-743 (Yondelis; PharmaMar)DNAIn combination with liposomal doxorubicin in relapsed ovarian cancerNDA voluntarily withdrawn following a request by the FDA for an additional phase III study, July 2009; approved by EMEA on the basis of same data showing 1.5-month PFS benefit, no OS benefit(62, 63)
Satraplatin (Spectrum and GPC Biotech)DNAHRPCGPC Biotech withdrew NDA filed for accelerated approval on the basis of ODAC recommendation that the FDA should wait for the survival analysis of the SPARC trial, July 30, 2007(44, 64, 65)
Oblimersen (Genasense; Genta)Bcl-2 antisense oligodeoxy-nucleotide G3139In combination with fludarabine and cyclophosphamide for patients with relapsed and/or refractory CLLODAC voted no for reasonable likelihood of clinical benefit, the threshold for accelerated approval.(66, 67)
FDA recommended that PFS or TTP be used as primary endpoint, rather than response rate, September 25, 2006
Atrasentan (Xinlay; Abbott)SERA(TM)HRPC that has spread to the boneODAC did not recommend approval of NDA, on the basis of TTP analysis, September 13, 2005(59, 68–70)
Gefitinib (Iressa; AstraZeneca)Mutated EGFRLung cancerNo survival benefit in unselected patient population. FDA restricted access to gefitinib, June 17, 2005(71, 72)

Abbreviations: CLL, chronic lymphocytic leukemia; EMEA, European Medicines Agency; HRPC, hormone-refractory prostate cancer; NHL, non-Hodgkin lymphoma; OS, overall survival; SERA(TM), selective endothelin-A receptor antagonists; sNDA, supplemental New Drug Application; SPA, special protocol assessment; SPARC trial, Satraplatin and Prednisone Against Refractory Cancer; TTP, time to progression; VEGFR, VEGF receptor.