Torrey Cope looks at the recent FDA emphasis on the challenges of a China-only trial strategy. He explores the FDA concern that a China-only clinical trial will be unable to prove that a drug is suitable for the U.S. population, and considers the regulatory requirements for U.S. approvals based on ex-U.S. trial data.

Recent developments relating to the use of China-only clinical trials for seeking approval in the U.S. have left many Chinese pharma companies wondering whether it’s possible to use China-only trials to get U.S. approval. It is, but those seeking to do so now face a number of challenges.

At the broadest level, the U.S. Food and Drug Administration (FDA) wants to be satisfied that ex-U.S. data are applicable to the U.S. population and medical practice. Among other things, this generally requires consideration of a variety of intrinsic (genetic and physiologic) and extrinsic (cultural and environmental) factors that may influence whether data from one population are applicable to another.

We have recently seen evidence of some changes in the FDA’s attitude towards data from China-only trials. In 2019, the head of the FDA’s oncology centre, Dr. Richard Pazdur, made comments at the AACR conference which suggested an openness to applications with clinical data generated only in China, depending on the quality of the actual data.

Earlier this year, however, the FDA made statements about the challenges of a China-only approach to U.S. approval in connection with its review of an application for a drug to treat non-small cell lung cancer. These statements focused on the need for consideration of class- and product-specific trial design issues, such as having a comparator arm and end points that are applicable to the U.S. population and medical practice, as well as potential differences in known and unknown characteristics of foreign patients compared to U.S. patients.

The non-small cell lung cancer drug example demonstrates how complicated the issue of data from China-only trials can become once the FDA begins to consider a specific application for a specific product. It also shows how the FDA’s views on the acceptability of data from China-only clinical trials can change quite quickly. In the above example, the FDA pointed out that the treatment paradigm for non-small cell lung cancer had changed dramatically between 2019 — the time of Dr. Pazdur’s original statement — and 2022 when the FDA actually came to consider an application for a new treatment in that area.

Generally, these concerns are being raised in a climate where the FDA has strongly emphasised that trials for U.S. approval should reflect the diversity of ethnic subgroups in the U.S. population, and has expressed strong interest in making multiregional clinical trials (MRCTs) the new standard for global drug development. The FDA has stressed that because of the push for more diversity and more MRCTs, single country trials are, in its own words, ‘a step backward.’

In such climate, we should expect that applications for U.S. approval based on China-only trials will be scrutinized on a class-by-class and a product-by-product basis. The best way to guard against rejection is to seek and carefully consider FDA input throughout the development process. Companies can also mitigate risk by ensuring they review the relevant legal standards, FDA guidance, and precedents.