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.
Highlights
Recent improvements in the understanding of cancer biology have posed new challenges for drug development in oncology
A personalized approach for drug development was associated with faster clinical development (Investigational New Drug [investigational new drug (IND)] to New Drug Application [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
More personalized drugs had the initiation of their clinical development (IND submission) during the contemporary period of time (2001–2010) compared to non-personalized drugs (75% of personalized drugs were developed between 2001 and 2010 while 42% of nonpersonalized drugs were developed in this time frame; P = .0186)
Summary
Recent improvements in the understanding of cancer biology have posed new challenges for drug development in oncology. New agents aiming to target these specific alterations are emerging and entering the drug development pathway. The March 2006 Food and Drug Administration (FDA) critical path report stressed that the development of biomarkers and streamlining of clinical trials were major priorities for medical product development [5]. Incorporating biomarkers for treatment selection in cancer therapy holds the promise of enhancing efficacy of new treatments and improving the success of drug approvals [6]. We previously showed that the incorporation of a biomarker-driven rationale for drug development (personalized/precision therapy strategy) was associated with improvements in response rate, progression-free and overall survival for FDA-approved anticancer agents [7]
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