FDA Rejects Camrelizumab-Rivoceranib Combo for Liver Cancer Over Manufacturing Issues

FDA Rejects Hengrui and Elevar's Liver Cancer Combo for Second Time

The U.S. Food and Drug Administration (FDA) has once again issued a complete response letter (CRL) to Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics for their combination therapy of camrelizumab and rivoceranib in first-line liver cancer treatment. This marks the second rejection for the PD-1 inhibitor and VEGFR inhibitor combination, with manufacturing issues cited as the primary concern.

Manufacturing Woes Continue

The FDA's latest decision comes after a previous rejection in May 2024, which was also attributed to manufacturing deficiencies at Hengrui's facility in China. While Hengrui reported that a January 2025 reinspection confirmed resolution of previous shortfalls, the agency has now raised three new issues requiring improvement.

Hengrui stated in a filing to the Shanghai Stock Exchange that the company will maintain close communication with the FDA and take measures to address the specific reasons for rejection. The pharmaceutical firm aims to resubmit the application as soon as possible in hopes of obtaining approval.

Clinical Efficacy and Market Landscape

Despite the regulatory setback, the camrelizumab-rivoceranib combination has shown promising clinical results. The final analysis from the phase 3 Cares-310 trial demonstrated that the combo reduced patients' risk of death by 36% compared to Bayer's Nexavar in first-line unresectable hepatocellular carcinoma. Patients receiving the combination lived a median of 23.8 months, versus 15.2 months for the control group.

The liver cancer treatment landscape in the United States currently includes established options such as Roche's Tecentriq-bevacizumab combination and AstraZeneca's Imfinzi-Imjudo duo. Bristol Myers Squibb is also awaiting an FDA decision for its Opdivo-Yervoy combination, with a target decision date set for April 21.

Global Regulatory Strategy

While facing challenges in the U.S. market, Hengrui and Elevar are pursuing approvals in other regions. Elevar plans to submit an application for the camrelizumab-rivoceranib combination to the European Medicines Agency in September 2025. The combo has already received approval for first-line liver cancer treatment in China, having been cleared in January 2023.

Dr. Saeho Chong, CEO of Elevar, expressed surprise at the FDA's decision, noting recent positive interactions and final label negotiations with the agency. He emphasized that the rejection was solely due to unresolved site remediation at the camrelizumab facility and not related to clinical data or issues with rivoceranib.