Evolving Landscape of New Drug Approval in Japan and Lags from International Birth Dates: Retrospective Regulatory Analysis

Tanaka, Mototsugu; Idei, Mayumi; Sakaguchi, Hiroshi; Kato, Ryosuke; Sato, Daisaku; Sawanobori, Kenji; Kawarasaki, Shuichi; Hata, Toshiyuki; Yoshizaki, Asako; Nakamura, Miki; Ikuma, Mutsuhiro

doi:10.1002/cpt.2080

Cited by 35 publications

(35 citation statements)

References 28 publications

(81 reference statements)

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“…Although Sakigake thus requires the will to achieve the first‐in‐world approval in Japan, the system is also open to global sponsors. In this study, 1/4 of the sponsors for Sakigake products were from overseas, and this proportion was higher than that for the new drugs with first‐in‐approval in Japan, 6 suggesting that overseas manufacturers actively use this system. Sakigake, as well as BTD in the USA and PRIME in the EU, does not exclude the overlap designations.…”

Section: Discussionmentioning

confidence: 65%

“…(C) The number of new drugs and the median drug lags from the international birth dates in each therapeutic area (with >8 products) among the drugs with new active substances approved in Japan from 2008 to 2019. The data in this panel of the Figure are not actually from this paper but from prior work 6 …”

Section: Resultsmentioning

confidence: 99%

“…Second, MHLW launched the promotion programme for the development of unapproved or off‐label drugs in 2009 to address the issue of unapproved drugs or off‐label uses of drugs, which are already available overseas but not in Japan. These measures resulted in a certain reduction in the drug lag in Japan; however, there remain substantial lags behind the USA and EU 6 …”

Section: Introductionmentioning

confidence: 99%

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Achievements and challenges of the Sakigake designation system in Japan

Tanaka

Idei

Sakaguchi

et al. 2021

Brit J Clinical Pharma

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The Sakigake designation system (Sakigake) has been launched to encourage the pioneered development of innovative new medical products for the effective treatment of severe illness in Japan, which allows leveraging the several advantages in prioritized consultation, rapid review, premium drug pricing and extended data‐protection period. We retrospectively analysed the Sakigake products including drugs and regenerative medical products to clarify the achievements and the future issues in this system. From April 2015 to August 2020 (the first 5‐year trial period of Sakigake), 37 products were designated, and 10 of those were approved in Japan in which 7 new active substances achieved the first‐in‐world approvals. Oncology, neurology and cardiovascular disease were the major therapeutic areas, and those 3 accounted for 75.7% of all products. Sakigake achieved some first‐in‐world approvals by the Pharmaceuticals and Medical Devices Agency/the Ministry of Health, Labor and Welfare of innovative new medical products, although in some therapeutic areas, there remains room in stimulating drug development.

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Section: Discussionmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Achievements and challenges of the Sakigake designation system in Japan

Tanaka

Idei

Sakaguchi

et al. 2021

Brit J Clinical Pharma

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“…The drug lag is a critical issue for patients with lifethreatening diseases or serious conditions that could cause irreversible disease progression [5,8]. For pediatric and/or rare diseases, there is an even higher risk of delay in drug approval in Japan, which further prolongs the drug lag [9].…”

Section: Data Source and Analysesmentioning

confidence: 99%

Evaluation of Drug Lags in Development Initiation, New Drug Application and Approval Between Japan and the USA and the Impact of Local Versus Multi-regional Clinical Trials

2021

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Background Drug time lags occur between the date that new drugs are first approved, often in the USA, and approval is granted in other countries. Multi-regional clinical trials (MRCTs) are a key strategy for simultaneous global development and regulatory submission of new drugs. However, no studies have evaluated the impact of MRCT versus local development on key time points in the drug development lifecycle between the USA and Japan. It is important for pharmaceutical companies planning drug development in Japan to understand when they can start development, when they can catch up in case of development initiation delay, length of time the development period might take, and amount of time that market exclusivity is lost, if Japan does not participate in the MRCT. Objective The aim of this study was to investigate differences in drug lag in development initiation, New Drug Application (NDA) submission and drug approval, as well as differences in the development and review periods, by local trials and MRCTs between Japan and the USA. We also assessed the advantages and disadvantages of MRCTs for these lags in Japan. Methods We analyzed drug approvals in Japan between 2016 and 2020 and divided them into local and MRCT groups. Lags in development initiation, NDA submission, and approval of new drugs were calculated by subtracting each date in Japan from the corresponding date in the USA. Our study period was divided into three periods based on the International Conference on Harmonization (ICH) E17 guideline, published in 2017, and the guideline for the Phase I trials in the Japanese population prior to MRCTs, published in 2014. In addition, subgroup analyses by therapeutic area, regulatory background, modality, capital style, and sales ranking (2020) were conducted. ResultsWe analyzed 174 approvals in Japan and the USA. The differences in the drug lags for development initiation, NDA submission, and approval between the local and MRCT groups were 4.9, 3.5, and 3.2 years, respectively. All three lag times were shorter for the MRCT group than the local group. A development initiation lag in the local group has expanded since publication of the guidelines. Conclusions For the people of Japan, important drug lags were identified in development initiation, NDA submission, and drug approval dates between local trials and MRCTs that include Japan. It is difficult to recover fully from the delay caused by local development, and it is important to understand the further expansion of drug lags, in cases where Japan is not involved in the MRCT.

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“…We have recently studied new drugs with Japan‐first approvals 7 and found that several new drugs required a long review period. Some important issues may underlie the review history for new drugs with delays in approval times.…”

Section: Introductionmentioning

confidence: 99%

Rationales of delay and difference in regulatory review by Japan, the USA and Europe among new drugs first approved in Japan

Tanaka

Idei

Sakaguchi

et al. 2021

Brit J Clinical Pharma

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To clarify the rationales of delay or difference in the review of new drug applications among regulatory authorities for new drugs, those first approved in the world being in Japan.Methods: Among 80 new drugs first approved in Japan from 2008 to 2019, we identified those subsequently approved in the USA or Europe. Significant delays in approval time (boxplot outliers) and the rationales for the delays were assessed among the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).Results: Of the 80 Japan-first approvals, 25 and 24 were approved in the USA and Europe, respectively, and their median approval times in Japan, the USA and Europe were 285, 334 and 477 days, respectively. Significant delays were identified for pirfenidone (1806 days, FDA), alogliptin benzoate (1856 days, FDA), insulin degludec (1457 days, FDA) and romosozumab (750 days, PMDA; 994 days, FDA; 748 days, EMA). Due to concerns about cardiovascular risk, alogliptin benzoate and insulin degludec were requested for additional clinical trials by the FDA, and romosozumab required a much longer review period than the standard approval time in all three regions.Conclusions: Among the new drugs significantly delayed in approval time in Japan, the USA or Europe, there were some differences in the requirements, the participating regions and the assessment of clinical trials. The regulatory views on the cardiovascular risk also differed among the three regions. These divergences may be associated with the differences in approval histories.

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Evolving Landscape of New Drug Approval in Japan and Lags from International Birth Dates: Retrospective Regulatory Analysis

Cited by 35 publications

References 28 publications

Achievements and challenges of the Sakigake designation system in Japan

Achievements and challenges of the Sakigake designation system in Japan

Evaluation of Drug Lags in Development Initiation, New Drug Application and Approval Between Japan and the USA and the Impact of Local Versus Multi-regional Clinical Trials

Rationales of delay and difference in regulatory review by Japan, the USA and Europe among new drugs first approved in Japan

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