The U.S. Food and Drug Administration (FDA) has delivered a second rejection to the liver cancer combination therapy jointly developed by Chinese pharmaceutical giant Jiangsu Hengrui Medicine and South Korean partner HLB, according to regulatory filings released this week.
The combination therapy, targeting advanced hepatocellular carcinoma (HCC), received a Complete Response Letter (CRL) from the FDA, indicating that the application cannot be approved in its current form. This marks the second regulatory setback for the partnership's oncology program in the U.S. market.
Regulatory Challenges for the Combination Approach
The rejected application sought approval for a combination of Hengrui's tyrosine kinase inhibitor and HLB's investigational immunotherapy agent for patients with advanced liver cancer who have failed previous systemic treatments. The FDA cited concerns regarding efficacy data consistency across different patient populations and questions about the risk-benefit profile.
"The agency has requested additional clinical data to demonstrate consistent efficacy across global populations," said a spokesperson from Hengrui Medicine. "We remain committed to addressing these concerns and working closely with regulatory authorities to bring this potential treatment option to patients with limited alternatives."
Industry analysts note that this rejection reflects the increasingly stringent regulatory environment for oncology drugs, particularly those developed primarily with data from non-U.S. populations.
Market Implications and Strategic Response
The news sent shares of both companies lower, with HLB experiencing a more significant decline on the Korean exchange. The setback is particularly challenging for HLB, which has positioned the liver cancer program as a cornerstone of its oncology portfolio.
Dr. Michael Chen, an independent oncology analyst, commented on the development: "This second rejection raises important questions about the companies' regulatory strategy. Liver cancer presentations can vary significantly between Asian and Western populations, and these differences may not have been adequately addressed in the submission package."
Hengrui and HLB have indicated they will request a meeting with the FDA to discuss a path forward, which may include conducting additional clinical trials with greater representation of U.S. and European patients.
Liver Cancer Treatment Landscape
Hepatocellular carcinoma represents a significant global health burden, with approximately 800,000 new cases diagnosed annually worldwide. The disease has a particularly high prevalence in Asia due to the higher rates of hepatitis B infection, a major risk factor for liver cancer.
Current first-line treatments for advanced HCC include sorafenib and lenvatinib, with second-line options including regorafenib, cabozantinib, and immunotherapy combinations. However, response rates remain modest, and the five-year survival rate for advanced disease is below 20%.
The Hengrui-HLB combination had shown promising results in Phase 2 studies conducted primarily in China and South Korea, with objective response rates exceeding those of current standard therapies. However, a smaller U.S.-based cohort apparently did not demonstrate the same level of efficacy.
Broader Implications for Global Drug Development
This case highlights the ongoing challenges in global pharmaceutical development, particularly for companies based outside the traditional Western pharmaceutical hubs seeking to enter the lucrative U.S. market.
"We're seeing increasing scrutiny of applications based predominantly on data from Asian populations," noted Sarah Johnson, a regulatory affairs consultant specializing in cross-border pharmaceutical approvals. "The FDA is requiring more robust evidence that efficacy translates across different ethnic groups and practice settings."
For patients with advanced liver cancer, the rejection means a potentially promising treatment option remains unavailable in the U.S. market for the foreseeable future, underscoring the continued unmet need in this difficult-to-treat malignancy.
Meanwhile, in a separate development, China's National Medical Products Administration (NMPA) has accepted a New Drug Application for an oral influenza treatment tablet and approved a biosimilar version of Tepezza, demonstrating the continuing regulatory activity in the Chinese pharmaceutical market.
