TY - JOUR
T1 - An appraisal of drug development timelines in the Era of precision oncology
AU - Jardim, Denis Leonardo
AU - Schwaederle, Maria
AU - Hong, David S.
AU - Kurzrock, Razelle
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Drug development
KW - FDA
KW - Pharmacoeconomics
KW - Precision medicine
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U2 - 10.18632/oncotarget.10588
DO - 10.18632/oncotarget.10588
M3 - Article
C2 - 27419632
AN - SCOPUS:84982296374
SN - 1949-2553
VL - 7
SP - 53037
EP - 53046
JO - Oncotarget
JF - Oncotarget
IS - 33
ER -