Hengrui Pharma and Elevar Therapeutics have received a third complete response letter from the FDA for their camrelizumab and rivoceranib combination therapy.
The rejection marks more than two years of regulatory setbacks for the anti-PD-1/VEGFR combination, which was first declined by the FDA in May 2024.
U.S. regulators declined to approve the combination as a first-line treatment for unresectable or metastatic hepatocellular carcinoma, the most common form of liver cancer.
Unlike the previous two rejections, which centered on manufacturing deficiencies at Hengrui’s camrelizumab facility, this third CRL stems from problems identified at the plant producing rivoceranib.
The FDA identified deficiencies at the rivoceranib manufacturing site during an inspection conducted in April, according to Hengrui and HLB Group in separate announcements.
Hengrui noted that the rivoceranib manufacturer had passed an inspection conducted by EU authorities in 2025, a detail the company appears to view as relevant context for the dispute.
The HLB Group, parent company of Elevar Therapeutics, confirmed it received the complete response letter on July 9, with Korean news sources reporting the agency cited only manufacturing problems.
Critically, the latest CRL raises no concerns whatsoever about the clinical data underpinning the application, Hengrui confirmed in a securities filing in Shanghai.
That clinical data comes from the phase 3 CARES-310 trial, published in the Journal of Clinical Oncology, which randomly assigned 543 patients with unresectable HCC in a 1:1 ratio to receive the combination or sorafenib.
The trial demonstrated a median overall survival of 23.8 months with camrelizumab plus rivoceranib compared to 15.2 months with sorafenib, representing a hazard ratio of 0.64 with a one-sided P value below 0.0001.
Elevar refiled its newest application on January 23, 2026, following the second complete response letter it received in March 2025, making this the third rejection in roughly as many years.
Despite the repeated setbacks, both companies appear determined to press ahead and resolve the outstanding regulatory manufacturing issues rather than abandon the programme entirely.
“The company has thoroughly evaluated the regulator’s feedback and is taking steps to implement appropriate corrective measures,” Hengrui said in its Shanghai securities filing.
Elevar acknowledged that an FDA re-inspection of the manufacturing facility may be required to confirm that it meets current good manufacturing practice compliance requirements before any approval can proceed.
“The company is reviewing the contents of the letter and intends to work closely with the FDA to determine the appropriate path forward,” said Elevar chief executive Dong-Gun Kim.