New Jersey-based Elevar Therapeutics, a majority-owned subsidiary of HLB Co., Ltd., announced that the US FDA issued a Complete Response Letter (CRL) for the New Drug Application (NDA) for the VEGFR-2 inhibitor rivoceranib (Aitan) in combination with PD-1 targeted camrelizumab (AiRuiKa; SHR-1210) as a first-line systemic treatment for unresectable or metastatic hepatocellular carcinoma (HCC). The CRL delays what would have been a commercially significant US launch for a combination that has already achieved approval in China and recognition in major international clinical guidelines.
The FDA’s decision was attributable solely to manufacturing deficiencies identified during a current Good Manufacturing Practice (cGMP) inspection of a production site listed on the rivoceranib NDA. According to Jiangsu Hengrui Pharmaceuticals Co., Ltd., the camrelizumab biologics license application partner, the site in question underwent FDA cGMP inspection in April 2026 and had previously passed EU inspections in 2025. Both companies confirmed the CRL did not involve clinical data, safety, or efficacy concerns.
This is the second CRL for this application. The FDA issued a prior CRL on March 20, 2025, with Elevar resubmitting the NDA in January 2026. The resubmission was accepted with a PDUFA date of July 23, 2026, and Elevar had publicly stated its intent to ensure manufacturing facility readiness throughout the review process. The recurrence of a manufacturing-related CRL at the same stage of review indicates the inspection findings were not fully resolved prior to the PDUFA date.
Rivoceranib is an oral VEGFR-targeted tyrosine kinase inhibitor; camrelizumab is a humanized anti-PD-1 monoclonal antibody. The combination blocks tumor angiogenesis and restores immune-mediated anti-tumor activity. The Phase III CARES-310 trial demonstrated a median overall survival of 23.8 months, reported as the longest among first-line HCC treatments to date, with the final analysis published in The Lancet Oncology in December 2025. In the competitive first-line HCC space, Bristol Myers Squibb’s nivolumab plus ipilimumab combination received US FDA approval in April 2025, while atezolizumab plus bevacizumab and lenvatinib remain established options.