FDA Rejects HutchMed NDA Over China Trial Data
FDA has issued HutchMed a complete response letter on its NDA for surufatinib, indicated for treating pancreatic (pNETs) and extra-pancreatic (epNETs) neuroendocrine tumors. The agency letter said that a multi-regional clinical trial (MRCT) is required for U.S. approval, according to the company. “FDA determined that the current data package, based on two positive Phase 3 trials in China and one bridging study in the United States (U.S.), does not support an approval in the U.S. at this time,” the company says.
The NDA rejection is consistent with FDA’s recent position on oncology drug development programs that rely almost exclusively on clinical data from China (see earlier story). Earlier this year, FDA Oncology Center of Excellence director Richard Pazdur co-authored a Lancet comment piece that outlined a number of concerns with China-based trials, such as many being conducted using comparators that are not considered the current U.S. standard of care. He also said there is concern about data from a single foreign country because of its “generalizability” to American patients. Pazdur also supported the decades-long standard of MRCTs where the U.S. often was included with substantial enrollment. Now, it seems, many development programs have settled in China in what likely is a move to address Asian regulator concerns about trial diversity.
HutchMed said its NDA was based on data from its SANET-p and SANET-ep studies, two randomized double-blind Phase 3 trials in patients with advanced pNETs and epNETs conducted in China. It also included data from a company-sponsored bridging study conducted in the U.S. that suggested “similar safety and efficacy to the SANET study population in China,” it says. “In a 5/2020 pre-NDA meeting, HutchMed reached an agreement with the FDA that the two positive Phase 3 studies of surufatinib in patients with pNETs and epNETs in China, along with the bridging trial in the U.S. could form the basis to support a U.S. NDA submission. The FDA accepted the filing of the NDA on 6/30/2021.”
The company says the FDA letter is requiring a “MRCT that includes subjects more representative of the U.S. patient population and aligned to current U.S. medical practice. In addition, pandemic-related issues concerning inspection scheduling and access contributed to the FDA action. This action by the FDA is not related to any safety issues with surufatinib.”
Surufatinib is described by HutchMed as a novel, oral angio-immuno kinase inhibitor that “selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.”