An inspection of a facility making Elevar’s rivoceranib uncovered deficiencies, leading the FDA to reject a combination therapy that includes the drug. The rebuff is the third strike for the partners after the agency issued manufacturing-related denials for the other drug in the combo.
The FDA has again rejected a request for approval of Hengrui Pharma and Elevar Therapeutics’ oncology drug combination over manufacturing issues.
Hengrui and Elevar, a majority-owned subsidiary of South Korea’s HLB, are developing a combination of the oral tyrosine kinase inhibitor (TKI) rivoceranib and anti-PD-1 antibody camrelizumab. A Phase 3 trial linked the first-line use of the combination to longer overall survival than sorafenib, which Bayer sells as Nexavar, in people with unresectable or metastatic hepatocellular carcinoma. But manufacturing issues have plagued the companies’ attempts to bring the two drugs to market.
In 2024, the FDA rejected camrelizumab over deficiencies seen during a preapproval inspection (PAI) of a plant listed in the application for the anti-PD-1 antibody. The camrelizumab rejection, plus the FDA’s inability to complete clinical inspections amid travel restrictions, triggered the 2024 complete response letter (CRL) for rivoceranib.
In 2025, the FDA rejected camrelizumab after finding deficiencies during a reinspection of a plant listed in the application for the anti-PD-1 antibody. The camrelizumab rejection led the FDA to issue the 2025 CRL for rivoceranib.
The roles were reversed in the latest setback, with deficiencies at a rivoceranib plant leading the FDA to issue a CRL for camrelizumab. The problems arose at a rivoceranib production plant. The FDA issued a Form 483 listing deficiencies after inspecting the rivoceranib facility. The agency wants the facility team to provide satisfactory responses to the deficiencies before Elevar resubmits.
Once it receives the responses, the FDA may reinspect the facility to confirm compliance with current good manufacturing practices (cGMP). A PAI could follow the confirmation of cGMP compliance. Satisfactory outcomes from the cGMP and PAI assessments will be needed before the FDA is willing to approve rivoceranib and, by extension, camrelizumab.
Elevar is reviewing the FDA’s CRL and plans to work closely with the agency to find the right path forward, CEO Dong-Gun Kim said in a statement. The biotech remains committed to advancing rivoceranib and camrelizumab and “will engage with the FDA promptly,” Kim said.
