Approval gap of pharmacogenomic biomarkers and in vitro companion diagnostics between the United States and Japan

Abstract

What is known and objectivesIn vitro companion diagnostic devices (CDx) provide information on pharmacogenomic biomarkers (PGBMs) to enable the safe and effective use of targeted agents for personalized therapy. These devices require specific regulations that strike a balance between scientific evidence and financial burden. The aims were to compare approval of PGBMs and CDx in the USA and Japan and to help inform current discussions on personalized medicine.MethodsWe analysed published documentation from the USA and Japan for CDx and PGBMs, listed by the US Food and Drug Administration (FDA). Aspects evaluated were aim, approval state and therapeutic area. Coverage by the National Health Insurance in Japan was also investigated.Results and discussionThirty-eight PGBMs were listed in the FDA table as of March 2013. In the USA, the aim was efficacy in 55% (21/38). The largest therapeutic area was oncology (39%, 15/38). Fifty-three per cent (20/38) of the PGBMs had a corresponding CDx approved. Of the 38 PGBMs in the FDA table, six had no approved drug in Japan; in 16 of the remaining 32 PGBMs, the aim was efficacy. The largest therapeutic area was oncology (34%, 11/32). Of the 32 PGBMs, 15 were associated with an approved and/or covered CDx, with only 11 having an approved CDx. Four PGBMs had a covered CDx without prior approval in Japan.What is new and conclusionOur study confirms that there is still a substantial gap in the approval of PGBMs and CDx between Japan and the USA. Complementary coverage of unapproved CDx by the National Health Insurance, however, is raising access to a similar level in both countries. Because the number of expensive personalized medicines and CDx is increasing, patient access will continue to be an important challenge to healthcare systems in all countries.

Guidance for pharmacogenomic biomarker testing in labels of FDA-approved drugs

“…Although we lack an official list of drugs with biomarker information in the label for countries other than the United States, some authors found discrepancies between the United States, Europe, and Japan in the number of such drugs and the contents of the labels. [22][23][24] Moreover, the phrasing and the number of indications for a given drug may differ between the United States and Europe. 25 Shimazawa et al 23 found substantial discordances in labels between Japan, the United States, and the United Kingdom, but these discordances were low for the indications section of labels and for biomarkers with recommendations for genetic testing.…”

Pharmacogenomic biomarkers: Interpretation of information included in United States and Japanese drug labels

“…Therapeutic areas were determined by the code list of the Anatomical Therapeutic Chemical (ATC) classification system. 42 We updated the approval status of US and Japanese CDx based on our previous study 43 If the ATC code was not available, it was extrapolated from the therapeutic area of the drug.…”

International differences in companion diagnostic approvals: how are we able to manage the differences?

“…A previous study has confirmed a substantial gap in the approval of CDx between Japan and the USA [2]. Of the 38 PGBMs listed in the FDA table [6], 20 PGBMs had a corresponding CDx approved in the USA.…”

“…Clinical cost-effectiveness is considered in reimbursement decisions on CDx even in countries without a health technology assessment approach, such as the USA [14] and Japan [15]. Approved CDx are generally covered by the National Health Insurance in Japan [2], but FDA approval is not a guarantee of coverage for CDx in the USA [14]. Lack of evidence for the clinical use of many CDx has led payers to deny or restrict coverage [16].…”

“…One would expect approvals for CDx not to differ significantly across countries, given that regulatory authorities evaluate the same scientific data. Differences in regulations of CDx arise [2,3], however, from biological and non-biological factors. Although the significance of regulatory factors in CDx approval is recognized, these factors have rarely been the focus of systematic research.…”