FDA’s review of marketing applications based on clinical trials conducted solely or predominantly in China has become an unprecedented focus in recent years. In March 2022, FDA refused to approve Innovent and Eli Lilly’s BLA for sintilimab for treatment of non-squamous non-small cell lung cancer (“NSCLC”) based on a pivotal phase 3 clinical trial conducted exclusively in China. The rejection followed a landmark advisory committee meeting where FDA’s Oncologic Drugs Advisory Committee (“ODAC”) concluded that the pivotal phase 3 clinical trial conducted solely in China was insufficient to support approval of the sintilimab BLA because the trial “was not applicable to the U.S. population and U.S. medical practice” due to its single-country design. The ODAC voted 14-1 that an additional clinical trial would be required prior to approval of sintilimab in the U.S.
At the ODAC meeting, Harpreet Singh, associate director of FDA’s Oncology Center of Excellence, opined that “[r]ather than an isolated case, [the sintilimab BLA] reflects an increasing number of oncology development programs based solely on, or predominantly on, clinical data from China.” Shortly thereafter in May 2022, Hutchmed, another China-based, innovative drug manufacturer, indicated that it had received a complete response letter for its new drug application (“NDA”) for surufatinib for treatment of advanced neuroendocrine tumors where FDA raised concerns over the sufficiency of relying on China-only pivotal clinical data and a U.S. bridging study to support approval. By contrast, on October 27, 2023, Shanghai-based TopAlliance, or Junshi Biosciences, and its partner Coherus received approval for their BLA for Loqtorizi (toripalimab-tpzi)(“toripalimab”) for treatment of nasopharyngeal carcinoma (“NPC”) which was similarly based on clinical trials conducted predominantly in China. In November 2023, FDA approved HUTCHMED and Takeda’s Fruzaqla (fruquintinib) for metastatic colorectal cancer. Unlike others, this approval was based on an international clinical trial conducted in Australia, Europe, Japan and U.K. and the U.S. and a clinical trial conducted exclusively in China.
These events, among others, have raised a few questions. Why applications based on foreign clinical trial data alone result in different FDA decisions? What are FDA’s standards for approving an application based solely or partly on clinical trials conducted outside the U.S.? How can a sponsor demonstrate applicability of foreign clinical trial data to the U.S. population and medical practice? And what are the considerations for China-based and other non-U.S. drug developers seeking FDA approval of global drug development programs going forward? I wrote and published an article on the Food and Drug Law Journal to explain and provide recommendations.