FDA issues second rejection of liver cancer drug combo due to manufacturing issues
The FDA has again declined to approve a liver cancer treatment developed by Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics over manufacturing issues.
The combination therapy, which pairs the PD-1 inhibitor camrelizumab with the VEGFR inhibitor rivoceranib, was submitted for use as a first-line treatment for unresectable hepatocellular carcinoma. According to a regulatory filing by Hengrui, the FDA issued a second Complete Response Letter (CRL), citing unresolved issues related to manufacturing.
This latest rejection follows an earlier CRL issued in May 2024, which stemmed from deficiencies uncovered during an FDA inspection of Hengrui’s facility in Suzhou, China. At that time, the agency also noted an incomplete clinical trial site inspection.
Hengrui stated that while the issues raised in the original review have since been addressed, the FDA has now identified three new concerns at the same site, prompting further delays. The company has responded to these new findings but has not yet received feedback from the agency.
The manufacturing site in question belongs to Suzhou Suncadia Biopharmaceuticals, a Hengrui subsidiary responsible for producing camrelizumab. A prior inspection resulted in a 10-page Form 483, outlining lapses in data integrity, contamination control, and raw material handling.
Despite these findings, the application was resubmitted in October 2024 with updated clinical trial data. The final analysis from the Cares-310 Phase 3 trial showed a median overall survival benefit of 23.8 months with the drug combination, compared to 15.2 months for the control arm.
Because the therapy involves a fixed combination of two drugs, the FDA cannot approve rivoceranib alone in the U.S. market. Elevar’s parent company, HLB, confirmed this limitation in a separate regulatory filing. Outside of the U.S., the companies plan to seek European approval later this year, with a submission to the European Medicines Agency expected in September.