title: An appraisal of drug development timelines in the Era of precision oncology.
abstract: The effects of incorporating a biomarker-based (personalized or precision) selection strategy on drug development timelines for new oncology drugs merit investigation. Here we accessed documents from the Food and Drug Administration (FDA) database for anticancer agents approved between 09/1998 and 07/2014 to compare drugs developed with and without a personalized strategy. Sixty-three drugs were included (28 [44%] personalized and 35 [56%] non-personalized). No differences in access to FDA-expedited programs were observed between personalized and non-personalized drugs. A personalized approach for drug development was associated with faster clinical development (Investigational New Drug [IND] to New Drug Application [NDA] submission; median = 58.8 months [95% CI 53.8-81.8] vs. 93.5 months [95% CI 73.9-112.9], P =.001), but a similar approval time (NDA submission to approval; median=6.0 months [95% CI 5.5-8.4] vs. 6.1 months [95% CI 5.9-8.3], P = .756) compared to a non-personalized strategy. In the multivariate model, class of drug stratified by personalized status (targeted personalized vs. targeted non-personalized vs. cytotoxic) was the only independent factor associated with faster total time of clinical drug development (clinical plus approval phase, median = 64.6 vs 87.1 vs. 112.7 months [cytotoxic], P = .038). Response rates (RR) in early trials were positively correlated with RR in registration trials (r = 0.63, P = <.001), and inversely associated with total time of drug development (r = -0.29, P = .049). In conclusion, targeted agents were developed faster than cytotoxic agents. Shorter times to approval were associated, in multivariate analysis, with a biomarker-based clinical development strategy.
authors.affiliation: Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil.
authors.forename: Denis Leonardo
authors.initials: DL
authors.lastname: Jardim
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Schwaederle
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.affiliation: Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, CA, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017277:Drug Approval / Q000379:methods*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006801:Humans; D008495:Medical Oncology / Q000379:methods*; D057285:Precision Medicine / Q000379:methods*; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational
keywords: FDA; biomarkers; drug development; pharmacoeconomics; precision medicine