The third time is not the charm for Hengrui Pharma and Elevar Therapeutics’ star-crossed combination of camrelizumab and rivoceranib at the FDA.
U.S. regulators have declined to approve the anti-PD-1/VEGFR combo for a third time as a first-line treatment for liver cancer, Hengrui and Elevar’s parent company, HLB Group, said in separate announcements Friday.
The problem, again, is manufacturing. Only this time, the complete response letter (CRL) stemmed from deficiencies the FDA had identified in April at the plant producing rivoceranib, also known as apatinib, unlike the previous two rejections, which centered on Hengrui’s camrelizumab facility, according to the Chinese pharma. The rivoceranib manufacturer had passed an inspection by EU authorities in 2025, it noted.
Still, three CRLs do not necessarily mean three strikes and you're out for Hengrui and Elevar.
“The company has thoroughly evaluated the regulator’s feedback and is taking steps to implement appropriate corrective measures,” Hengrui said in a securities filing (Chinese, PDF) in Shanghai. “The company will actively communicate with the FDA and our partner, Elevar Therapeutics, to establish the next resubmission plan.”
Elevar “intends to promptly address the aforementioned deficiencies and resubmit the application for FDA approval,” HLB said in its own securities filing to the Korea Exchange.
As Elevar noted, a re-inspection by the FDA may be required to determine that the facility meets CGMP compliance requirements.
More than two years have passed since the FDA first snubbed the camrelizumab-rivoceranib regimen in May 2024. The second CRL arrived in March 2025. And Elevar refiled the newest application on Jan. 23, 2026.
The latest CRL does not raise any issues on clinical data, Hengrui said. For this application, the two companies provided updated final analysis from the phase 3 Cares-310 trial, which showed a 36% death risk reduction for camrelizumab and rivoceranib versus Bayer’s Nexavar in first-line unresectable hepatocellular carcinoma.
Chinese companies have long viewed follow-on PD-1 inhibitors as a viable entry point into the highly lucrative U.S. innovative drug market. However, these candidates have faced a string of regulatory and operational setbacks along the way.
In a high-profile decision that triggered ripple effects across the industry, the FDA in 2022 refused to approve Innovent Biologics’ then Eli Lilly-partnered Tyvyt, citing predominantly China-only data as a problem. Thanks to that policy, Novartis abandoned its U.S. submission plan in first-line non-small cell lung cancer for Tevimbra before returning the asset to BeOne Medicines, then known as BeiGene. The same fate met CStone Pharmaceuticals’ PD-L1 inhibitor sugemalimab and its partnership with EQRx, which was absorbed into Revolution Medicines in 2023.
Besides Hengrui, Fosun Pharma is also angling its China-approved PD-1 inhibitor serplulimab for an initial FDA approval in extensive-stage small cell lung cancer. Despite the positive phase 3 Astrum-005 trial, which showed the drug beat placebo, both added to chemotherapy, Fosun had to conduct a U.S. bridging study that compared serplulimab to Roche’s Tecentriq. With that study recently complete, Fosun is in discussions with the FDA about a potential filing this year.