During the COVID-19 pandemic, the clinical development of therapeutics progressed rapidly. However, regions outside the areas where most clinical development occurred experienced delayed access and had fewer options for new therapeutics. To adequately respond to future pandemics, these regions must be prepared to expedite the development of necessary therapeutics. In this study, we compared the clinical development of COVID-19 therapeutics between the USA and Japan and proposed strategies for enhancing global therapeutic deployment in future pandemics.

Cross-sectional analysis.

The regulatory documentation for COVID-19 therapeutics granted Emergency Use Authorization (EUA) in the USA or approved in Japan during the WHO-declared pandemic period (30 January 2020 to 5 May 2023) was analysed.

The development timelines and submitted data in both regions were analysed.

14 therapeutics were authorised in the USA compared with 9 in Japan, of which 8 were authorised in both countries. For all eight therapeutics, authorisation was obtained earlier in the USA, with an average difference of 4 months. The number of clinical studies submitted for authorisation was 1.0 in Japan and 4.0 in the USA. The data packages submitted for approval in the USA generally followed the standard structure for a typical application, including phase 1, 2 and 3 studies, whereas in Japan, phase 3 study data were often the primary focus.

Compared with the USA, fewer therapeutics were approved in Japan, and the approvals occurred later. Most therapeutics approved in Japan had previously received EUA in the USA, with Japanese approvals largely dependent on participation in large-scale global studies and the US review schedule. Application data in Japan were primarily based on data from large-scale global studies that had been submitted for the US application; the observed delay in approval was considered attributable to the time required for application preparation. In preparation for future pandemics, it will be necessary to establish systems that take these characteristics into account.

Traumatic brain injury (TBI) often causes permanent neurological dysfunction. Although no medication has been validated yet to prevent secondary injury of brain tissue, recent animal studies have reported that perampanel, a glutamine receptor antagonist, could improve the neurological functions of animals with TBI by mitigating the abnormal calcium influx and cell death around the site of primary injury. The present study aims to elucidate the efficacy of perampanel administration in improving the neurological function of patients with TBI.

The perampanel for alleviation of secondary injury in TBI trial is a multicentre, phase-II, open-label randomised controlled trial targeting patients with mild-to-moderate TBI. This trial will include adult TBI patients with a Glasgow Coma Scale score of 9–14 from five tertiary centres. Patients with epilepsy as a comorbidity, delayed presentation of symptoms (>24 hours after injury) or Injury Severity Score of ≥25 will be excluded. The study participants will be randomly assigned to either the perampanel group (2 mg/day) or the control group (fosphenytoin administered at a dose of 15–18 mg/kg/day, followed by 5–7.5 mg/kg/day of fosphenytoin). In both groups, the medication will be initiated within 12 hours of the TBI diagnosis and continued for 7 days. The antiepileptic drugs can be increased, changed or added as necessary if early post-traumatic seizures are observed. The primary outcome is favourable neurological outcome, defined as a Glasgow Outcome Scale Extended score of ≥5 at 90 days after the TBI diagnosis, which will then be compared between the groups through an intention-to-treat analysis.

The present study has been approved by the Certified Review Board of Keio at the principal institution (approval number: N20240004). Written informed consent will be obtained from all participants or their legal representatives. The results will be disseminated via publications and presentations.

Japan Registry of Clinical Trials (jRCTs031250067).