Nationalism in Japanese media coverage of domestic pharmaceutical products

In November, 2022, ensitrelvir, developed by one of the largest Japanese pharmaceutical companies (Shionogi, Osaka), was granted the first emergency-approval authorisation for patients with mild-to-moderate COVID-19, following the implementation of the emergency-approval system in May, 2022, by the Japanese Government.1Pharmaceuticals and Medical Devices AgencyDrug application review report for ensitrelvir.https://www.pmda.go.jp/drugs/2022/P20220719001/340018000_30400AMX00205000_A100_4.pdfDate: Nov 22, 2022Date accessed: March 23, 2023Google Scholar The new system allows regulatory approval for up to 2 years based on a presumption of efficacy and safety with immature clinical trial data conducted in a short timeframe in case of emergencies, such as a pandemic. After emergency approval, a regulatory reassessment based on additional data, such as a confirmatory clinical trial and real-world data on the drug, is required. During the regulatory assessment of the emergency approval of ensitrelvir, unusual controversy was aroused about preliminary results of a pivotal trial; the original primary endpoint of the protocol has been arbitrarily changed from the time until recovery from 12 COVID-19-related symptoms to five specific symptoms (ie, fatigue, fever, stuffy nose, sore throat, and cough). The study population for the analysis was narrowed down and the effect of shortening the resolution of symptoms was just 24·3 h faster than in the placebo group (167·9 h vs 192·2 h).2Yotsuyanagi H Ohmagari N Doi Y et al.A phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (phase 3 part).Medicine. 2023; 102e33024Crossref Scopus (6) Google Scholar, 3Conference on Retroviruses and Opportunistic Infections. Ensitrelvir for mild-to-moderate covid-19: phase 3 part of phase 2/3 study.https://www.croiconference.org/abstract/ensitrelvir-for-mild-to-moderate-covid-19-phase-3-part-of-phase-2--3-study/Date: Feb 22, 2023Date accessed: March 23, 2023Google Scholar Subsequently, after the emergency approval, additional data were presented at an academic meeting in February, 2023, suggesting that ensitrelvir might decrease the risk of post-COVID-19 condition (also known as long COVID).3Conference on Retroviruses and Opportunistic Infections. Ensitrelvir for mild-to-moderate covid-19: phase 3 part of phase 2/3 study.https://www.croiconference.org/abstract/ensitrelvir-for-mild-to-moderate-covid-19-phase-3-part-of-phase-2--3-study/Date: Feb 22, 2023Date accessed: March 23, 2023Google Scholar However, the data did not confirm a dose-dependent effect, and the reported 45% risk reduction was observed only in the subgroup of patients with high symptom scores. These data remain unpublished to date.4ShionogiCROI 2023 follow-up meeting.https://www.shionogi.com/content/dam/shionogi/jp/investors/ir-library/presentation-materials/fy2022/J_CROI_clean.pdfDate: Feb 22, 2023Date accessed: March 23, 2023Google Scholar Despite the ambiguous clinical evidence,1Pharmaceuticals and Medical Devices AgencyDrug application review report for ensitrelvir.https://www.pmda.go.jp/drugs/2022/P20220719001/340018000_30400AMX00205000_A100_4.pdfDate: Nov 22, 2022Date accessed: March 23, 2023Google Scholar, 2Yotsuyanagi H Ohmagari N Doi Y et al.A phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (phase 3 part).Medicine. 2023; 102e33024Crossref Scopus (6) Google Scholar, 3Conference on Retroviruses and Opportunistic Infections. Ensitrelvir for mild-to-moderate covid-19: phase 3 part of phase 2/3 study.https://www.croiconference.org/abstract/ensitrelvir-for-mild-to-moderate-covid-19-phase-3-part-of-phase-2--3-study/Date: Feb 22, 2023Date accessed: March 23, 2023Google Scholar Japanese mass media enthusiastically covered the drug as if it was a miracle cure, possibly because it was developed by a Japanese company rather than a foreign company. Understandably, the propagandisation of such preliminary results of ambiguously designed clinical trial data, and data of a non-approved indication, such as long COVID, that has not yet been academically peer-reviewed,4ShionogiCROI 2023 follow-up meeting.https://www.shionogi.com/content/dam/shionogi/jp/investors/ir-library/presentation-materials/fy2022/J_CROI_clean.pdfDate: Feb 22, 2023Date accessed: March 23, 2023Google Scholar is concerning because it could contribute to the undue promotion and use of the drug.5Tuccori M Convertino I Ferraro S et al.The impact of the COVID-19 “infodemic” on drug-utilization behaviors: implications for pharmacovigilance.Drug Safety. 2020; 43: 699-709Crossref PubMed Scopus (0) Google Scholar Such biased medical reports by Japanese mass media are not rare. Japan previously faced a similar issue with off-label use of favipiravir (FUJIFILM, Toyama) and ivermectin (Kowa, Nagoya) against COVID-19, other drugs manufactured in Japan, which were exuberantly highlighted in media coverage and endorsed by prominent political authorities before the results of clinical trials were released.6Ueda M Tanimoto T Murayama A Ozaki A Kami M Japan's drug regulation during the COVID-19 pandemic: lessons from a case study of favipiravir.Clin Pharmacol Ther. 2022; 111: 545-547Crossref Scopus (15) Google Scholar In the background of such biased media coverage, there is a shared urgency about Japan's declining pharmaceutical industry among stakeholders and the Government. The worldwide pharmaceutical market had a 5·1% growth from 2017 to 2021, whereas only Japan had a slight decline or stagnation, and the importation of foreign-made drugs is increasing.7IQVIA Institute for Human Data ScienceThe global use of medicines 2022: outlook to 2026.https://www.iqvia.com/-/media/iqvia/pdfs/library/publications/the-global-use-of-medicines-2022.pdfDate: Jan 15, 2022Date accessed: March 26, 2023Google Scholar Although there is growing expectation for the development of domestic products for economic growth, whether a policy that unscientifically favours domestic companies can effectively benefit both Japanese citizens and the larger medical science community, rather than solely supporting domestic pharmaceutical companies, is disputable. For the mass media to maintain a rational and neutral stance towards science is essential to avoid becoming a mouthpiece of manufacturers with exaggerated commercial interests. TT receives personal fees from Medical Network Systems (MNES) and Bionics unrelated to this Correspondence. HS received personal fees from TAIHO Pharmaceutical unrelated to this Correspondence. AO receives personal fees from MNES, TAIHO Pharmaceutical, and Kyowa Kirin unrelated to this Correspondence. HH and KT declare no competing interests. We thank Shai Mulinari for the fruitful discussion.