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ES10 - Oncology Drug Approval: Challenges and Opportunities (ID 13)
- Event: WCLC 2019
- Type: Educational Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
ES10.02 - Japan Pharmaceuticals and Medical Devices Agency (Now Available) (ID 3206)
13:30 - 15:00 | Presenting Author(s): Sumimasa Nagai
The Pharmaceuticals and Medical Devices Agency (PMDA) and the Ministry of Health, Labour and Welfare (MHLW) are responsible for reviewing applications and approving the marketing authorization of drugs, medical devices, and regenerative medicines in Japan. All applications for marketing authorization in Japan are submitted to the PMDA. The PMDA conducts scientific review. Review reports prepared by the PMDA are then submitted to MHLW. The MHLW approves the marketing authorization.
Japanese regulation has two categories of regulatory review: standard review and priority review. Priority review is applied to orphan drugs and products designated by the MHLW. Other than orphan drugs, the MHLW designates medical products as priority review products based on the following criteria described: 1. Seriousness of the target disease and 2. Clinical usefulness of the drug: no standard therapy exists, and clinical usefulness is superior to the existing products in terms of efficacy, safety, or the patient’s quality of life. The target total review time for standard review products and priority review products is 12 months and 9 months, respectively.
The conditional and term-limited approval system has been first introduced for regenerative medical products since November, 2014. Regenerative medical products may be granted conditional and term-limited approval if their efficacy can be assumed and safety is confirmed in early-phase (phase I and/or II) registration trials. In the approval system, sponsors of the products must confirm their efficacy and safety after marketing authorization in postmarketing clinical studies etc and by resubmitting applications for regular approval within a predetermined period (not more than 7 years). The conditional and term-limited approval for regenerative medical products is similar to the accelerated approval in the US.
In addition, the conditional approval system for drugs has been newly instituted since October, 2017 in Japan. This may be granted if all of the following requirements are met: 1. seriousness of the target disease, 2. clinical usefulness of the drug: no standard therapy exists, and clinical usefulness is superior to the existing products in terms of efficacy, safety, or quality of life, 3. it is difficult or it takes too long time to conduct a confirmatory study, 4. exploratory clinical studies can show efficacy and safety, and 5. surveillance or clinical studies must be conducted as post-marketing requirement. Because these requirements include the requirements for priority review (seriousness of the target disease and clinical usefulness of the drug), drugs granted conditional approval can automatically enjoy priority review. Moreover, the requirement for conditional approval “it is difficult or it takes too long time to conduct a confirmatory study” in Japan is totally different from accelerated approval based on surrogate endpoint in the US. The requirement is similar to the requirement for marketing authorization under exceptional circumstances “companies cannot provide comprehensive clinical data because of the rarity of the disease” in the EU. Although the requirements for conditional approval for drugs in Japan include “surveillance or clinical studies must be conducted as post-marketing requirement”, the term of validity for conditional approval of drugs in Japan is not established, which is different from the conditional and term-limited approval for regenerative medical products in Japan. As of May 31, 2019, only lorlatinib for ALK fusion-positive non-small cell lung cancer and pembrolizumab for MSI-high solid cancer have been granted conditional approval for drugs in Japan. Conducting confirmatory comparative studies is not included in postmarketing requirements for the both drugs.
The MHLW instituted in 2015 the SAKIGAKE (meaning pioneer or forerunner in Japanese) designation system for medical products for diseases in urgent medical need of innovative therapy and that may satisfying the following two conditions: 1. The medical product has been first developed in Japan, and a sponsor is planning to submit a marketing authorization application; and 2. Prominent effectiveness can be expected based on data from the mechanism of action, non-clinical studies, and early-phase clinical studies. Advantages of sponsors who have medical products granted SAKIGAKE designation are as follows: prioritized consultation (reduced waiting time), substantial pre-application consultation, prioritized review (target total review time of 6 months only for drugs, devices, and IVDs), assigning a PMDA manager as a concierge, and an extension of the reexamination period. Total review time for SAKIGAKE-designated regenerative medical products is not established. Although the SAKIGAKE designation is similar to a breakthrough therapy designation in the US and PRIME in the EU, the requirement “the medical product has been first developed in Japan” and the advantage of specific shortened total review time are unique to the SAKIGAKE.
Companion diagnostics (CDx) are important for oncology drug development. Current regulatory considerations regarding CDx and tumor profiling test in Japan are similar to those in the US. As of May 31, 2019, three next generation sequencing-based oncology panel tests have been approved as CDx and/or tumor profiling test in Japan. However, more flexible regulations regarding CDx are necessary for efficient clinical practice and drug development.
I will give an overview of regulatory frameworks and challenges regarding oncology drugs and companion diagnostics in Japan.
・Nagai S, Ozawa K. Regulatory approval pathways for anticancer drugs in Japan, the EU and the US. Int J Hematol. 2016;104:73-84.
・Nagai S, et al. Evolving Japanese regulations on companion diagnostics. Nat Biotechnol. 2016;34:141-144.
・Salgado R, Solit DB, Rimm DL, Bogaerts J, Canetta R, Lively T, Lyerly K, Span PN, Bateman-House A, Makady A, Bergmann L, Nagai S, et al.; IBCD-Faculty. Addressing the dichotomy between individual and societal approaches to personalised medicine in oncology. Eur J Cancer. 2019;114:128-136.
・Lyerly HK, Ren J, Canetta R, Kim GH, Nagai S, et al. Global Development of Anticancer Therapies for Rare Cancers, Pediatric Cancers, and Molecular Subtypes of Common Cancers. J Glob Oncol. 2018;4:1-11.
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