HLB's liver cancer drug makes fourth FDA bid after manufacturing fixes

HLB has launched its fourth attempt to win FDA approval for its first-line liver cancer treatment, pressing ahead despite repeated requests for additional information from the US regulator.

HLB said Monday that its US subsidiary Elevar Therapeutics and Chinese partner Hengrui Pharmaceuticals resubmitted a new drug application and a biologics license application to the FDA on Thursday (local time), seeking approval of the rivoceranib and camrelizumab combination therapy as a first-line treatment for hepatocellular carcinoma.

The submission is the third resubmission since the original filing, marking the fourth approval application in total.

Elevar and Hengrui first filed for approval in May 2023, but received a complete response letter in May 2024 citing manufacturing facility inspection and clinical site issues. They resubmitted in September 2024, only to receive a second CRL in March 2025. A third application filed on Jan. 23 of this year also ended in failure when the FDA issued a third CRL on July 9. The two companies then continued discussions with the FDA, completed their response to the outstanding manufacturing facility inspection procedures, and filed the current fourth application.

The review will again rely on data from the global Phase 3 trial (CARES-310) as its primary evidence. In the trial involving patients with unresectable or metastatic hepatocellular carcinoma, the rivoceranib-camrelizumab combination arm achieved a median overall survival of 23.8 months — a 36% reduction in the risk of death compared with the sorafenib control arm (15.2 months), with a hazard ratio of 0.64 (95% CI 0.52–0.79, P<0.0001). This represents the longest survival duration reported in any first-line liver cancer trial to date.

The final Phase 3 results were published in The Lancet Oncology last December. Even before formal regulatory approval, the data's clinical value has been recognized: the combination has been listed as a first-line treatment recommendation in both the Barcelona Clinic Liver Cancer staging system guidelines and the European Society for Medical Oncology clinical practice guidelines.

"Unresectable liver cancer remains an area of high unmet medical need, and we have been focused on providing patients and clinicians with a new option," said Kim Dong-geon, chief executive of Elevar Therapeutics. "With the manufacturing facility inspection procedures now concluded, we will work closely with the FDA to ensure the review process concludes successfully, based on the therapeutic value demonstrated in clinical trials."

The latest resubmission addresses the chemistry, manufacturing and controls issues that led to the three previous rejections, clearing the way for the FDA to reassess the drug's clinical data on its own merits. Whether this Korean oncology drug, which has persistently pursued regulatory approval, can finally clear the last hurdle to US commercialization remains to be seen.