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.

Keywords: FDA; biomarkers; drug development; pharmacoeconomics; precision medicine.

Figure 1. Flow chart of drug selection

Figure 2. Development phases of drugs approved between 09/1998 and 07/2014 for the treatment of advanced cancers

Figure 3. Reported response rates in phase I trials in all tumors (A) and tumors in which the drug was eventually approved (B) and total time of drug development (IND submission to NDA/BLA approval) in months

Total time of development was inversely associated with response rate. Reported response rates in phase I trials in all tumors (C) and tumors in which the drugs were eventually approved (D) and response rates in registration trials of the same drug. Phase I trials were matched to registration trials as described in methods section and previously published. [31].