(B-069) Differences in Characteristics and Clinical Benefits of Pivotal Trials Supporting Regulatory Approval of “Breakthrough” Drugs in the US and China

Background: While clinical testing for investigational drugs can take six to eight years, regulators apply flexibilities to promising treatments addressing unmet medical needs. The FDA introduced the Breakthrough Therapy Designation (BTD) in 2012, followed by a similar pathway in China in 2020. Whether these pathways effectively balance patient benefits and drug access remains a key concern in drug policy research. However, no study has systematically compared BTD implementation in the U.S. and China. Our research aims to fill this gap and provide insights for future drug approvals.

Objectives: This study compared the BTD programs, the characteristics of designated drugs in each country, and the clinical benefits demonstrated in their pivotal trials. Our objective is to systematically assess the implementation effects of BTD in both the US and China, conduct a meaningful comparative analysis, and ultimately provide valuable recommendations for global regulatory practices.

Methods: We identified new drugs approved by the FDA and the NMPA between January 2021 and December 2023 using the FDA’s Drugs@FDA database and China’s CDE Annual Drug Evaluation Reports, focusing on first indications approved by the FDA and both category 1 innovative drugs and category 5.1 imported new drugs in China. BTD-designated drugs were identified using regulatory lists, review reports, and databases. We extracted approval details, pivotal trial data, and expedited pathways from public reports. Clinical value assessments were obtained from German and French agencies, with statistical analyses conducted using R version 4.3.0.

Results: Our cohort included 142 FDA-approved and 179 NMPA-approved new drugs from 2021 to 2023, with BTD granted to 25.4% and 15.6%, respectively (P = 0.04). BTD-designated drugs were more likely to be cancer therapies and qualify for additional expedited pathways, such as accelerated or conditional approval, compared to non-BTD drugs. Pivotal trials for FDA-approved BTD drugs tended to involve fewer trials and smaller patient populations, while NMPA-approved BTD drugs showed no significant differences in trial size. Clinical benefit analysis indicated higher benefits for FDA-approved BTD drugs, though ratings from German and French HTA agencies suggested that both FDA and NMPA BTD drugs had limited added therapeutic value over existing treatments.

Conclusions: This study revealed differences between China and the United States in the implementation of the BTD expedited program. FDA-approved BTD drugs demonstrated significantly higher clinical benefits, whereas NMPA-approved drugs did not show markedly greater efficacy benefits. This highlights the need for long-term evaluation of BTD program to enhance drug accessibility and align with global standards.