The drug lag and associated factors for orphan anticancer drugs in Japan compared to the United States

Abstract

The approval of orphan anticancer drugs in Japan has increased to meet high social demand. Drug lag, namely the approval lag of new drugs, is recognized as a social issue in Japan. We investigated the approval lag and its components, submission lag and review-time lag, between Japan and the United States (US) to reveal whether an approval lag still exists, and to identify potential factors that may contribute to reducing the approval lag. Anticancer drugs approved in Japan between April 2004 and November 2017 were investigated using publicly available information. Results showed that the median approval lag of orphan anticancer drugs in 2016-2017 was 727.0 days (interquartile range, IQR, 310.0-1054.3). The approval lag was significantly correlated with the submission lag (correlation coefficient = 1.00, P < 0.001) but not with the review-time lag (correlation coefficient = -0.16, P = 0.22). The submission lag was significantly longer for orphan anticancer drugs than non-orphan drugs (median, 712.5 days [IQR, 186.0-1448.3] vs. 387.0 days [92.8-1096.0], P = 0.023). External collaboration in drug development was associated with a longer submission lag (coefficient = 762.1, P = 0.017), while breakthrough therapy designation in the US was associated with a shorter submission lag (coefficient = -832.8, P = 0.035). In conclusion, we revealed that an approval lag for orphan anticancer drugs still existed in 2016-2017. A submission lag for orphan anticancer drugs was the main component affecting the approval lag, and was longer than that for non-orphan drugs. External collaboration in drug development may be a potential factor in reducing the submission lag for orphan anticancer drugs.

Drug Lag and Associated Factors for Approved Drugs in Korea Compared with the United States

“…The criteria for orphan drug designation have evolved; however, the key criteria are for prevalence and the medical plausibility over alternative treatments as well as the unmet needs of the patients [ 30 , 31 ]. Several previous studies have evaluated the impact of whether drugs were was approved as an orphan drug in the US and the regulatory pathway, including priority review, accelerated approval, and breakthrough therapy [ 3 , 12 ]. Our findings show that the regulatory pathway in the US did not have a significant effect on drug lag.…”

“…Preparing the regulatory pathway of the local new drug application (NDA) requires generating local specific data for the target indication and population to address the potential ethnic difference of the efficacy or safety of the drug [ 9 , 10 , 11 , 12 ]. Bridging clinical studies are required to extrapolate the foreign clinical data to local populations for local regulatory approval [ 13 ].…”

Assessment of Drugs Approved by Public Knowledge‐Based Applications (Kouchi‐shinsei) During the Last Two Decades in Japan

“… 6 , 7 Furthermore, although drug lag had previously been marked for anticancer drugs, it may occur for drugs for orphan diseases in the future. 42 , 43 Clearly, patient access to drugs for orphan diseases is a global issue. 44 Thus, in the future, when considering the direction of public knowledge‐based application in Japan, we consider it necessary to apply this method of application to orphan diseases.…”

“…Moreover, drug lag has recently been eliminated in Japan [41], and it is assumed that public knowledge-based application has been useful in eliminating drug lag [6,7]. Furthermore, while drug lag had previously been marked for anti-cancer drugs, it may occur for drugs for orphan diseases in the future [42,43]. Clearly, patient access to drugs for orphan diseases is a global issue [44].…”

Comparison of Successful and Unsuccessful Cases of New Drug Approvals Based on the International Council on Harmonization E5 Guidelines in Japan

“…[8][9][10] However, it has been reported that the approval lag still exists in some therapeutic areas. [10][11][12][13] Shortening the development start lag is important for reducing a large approval lag. 14 In Japan, drug development may be pursued using bridging strategies if overseas (non-Japanese) MRCTs are under way.…”