Active Pharmaceutical Ingredient and Finished Product Facilities Receive Voluntary Action Indicated (VAI) Classification; Resubmission Follows Three-Month Correction Period
Phase 3 Clinical Trial Demonstrates Median Overall Survival of 23.8 Months and 36% Reduction in Risk of Death; FDA Review Timeline Pending
HLB (028300) has resubmitted its U.S. Food and Drug Administration (FDA) application for the combination therapy of rivoceranib and camrelizumab, which is being developed as a first-line treatment for hepatocellular carcinoma (liver cancer). With both the Active Pharmaceutical Ingredient (API) and finished product manufacturing facilities receiving "Voluntary Action Indicated" (VAI) status from the FDA, the production-related inspections that previously stalled the approval process have been successfully concluded. Building on the significant survival improvements confirmed in its global Phase 3 clinical trials, HLB is renewing its push to enter the U.S. market.
HLB announced on the 12th that its U.S. subsidiary, Elevar Therapeutics, and its Chinese partner, Hengrui Pharma, submitted the New Drug Application (NDA/BLA) for the rivoceranib-camrelizumab regimen to the FDA on the 9th (local time).
This resubmission comes approximately three months after the FDA issued a Complete Response Letter (CRL) in July. Since then, Elevar and Hengrui Pharma have focused on addressing manufacturing requirements, successfully concluding the FDA’s site inspections with VAI classifications.
VAI Status Secured for API and Finished Product Facilities
The primary hurdle for HLB’s liver cancer treatment in the previous review cycle involved Chemistry, Manufacturing, and Controls (CMC) issues. In 2024 and 2025, CMC concerns regarding camrelizumab were raised, while in July of this year, the FDA’s Current Good Manufacturing Practice (cGMP) inspection results for the rivoceranib API facility impacted the approval timeline.
Following the July CRL, the rivoceranib API facility received a VAI classification, and Hengrui Pharma submitted its Corrective and Preventive Actions (CAPA) regarding the findings at the finished product facility.
Earlier this month, the finished product facility was also granted VAI status. HLB stated on the 6th that the FDA had classified the regular cGMP inspection of that facility as VAI, and Elevar confirmed receipt of the inspection closing letter from Hengrui Pharma on the 3rd.
A VAI classification indicates that while some improvements were identified during the inspection, the FDA has determined that no immediate formal regulatory action is required. With both facilities now cleared, Elevar and Hengrui Pharma consulted with the FDA to finalize the resubmission.
Notably, the FDA’s July CRL did not raise any new concerns regarding clinical efficacy or safety, nor did it require additional clinical trials. The resubmission continues to rely on the results of the global Phase 3 "CARES-310" study.
23.8-Month Survival Rate: Reaffirming Phase 3 Success
The final analysis of the CARES-310 trial revealed a median overall survival (mOS) of 23.8 months for patients receiving the rivoceranib-camrelizumab combination, compared to 15.2 months for those in the sorafenib control group—a gain of 8.6 months. The risk of death was reduced by 36% compared to the control group (HR 0.64, 95% CI: 0.52–0.79).
HLB stated that this survival rate is among the longest reported to date in first-line liver cancer treatment trials. While direct comparisons across different clinical studies are challenging, the company maintains that these results demonstrate strong competitiveness against existing treatments.
The CARES-310 results were published in the international journal *The Lancet Oncology* last December. According to the company, the combination therapy has also been listed as a recommended first-line treatment option in the 2025 Barcelona Clinic Liver Cancer (BCLC) strategy and European Society for Medical Oncology (ESMO) guidelines.
FDA Review Timeline Awaited: Expanding Portfolio Beyond Cholangiocarcinoma
Upon formal receipt of the resubmission, the FDA will determine the review classification based on the scope and necessity of the additional documentation. Class 1 reviews typically take two months, while Class 2 reviews take six months. The specific classification for this resubmission and the target action date have not yet been determined.
Following the FDA approval of its cholangiocarcinoma treatment, lirafugratinib, in September, HLB is now moving to secure approval for its first-line liver cancer therapy. Success in the liver cancer market would significantly expand the company's oncology portfolio in the U.S.
"With the manufacturing facility inspection process concluded, we will work closely with the FDA to ensure a successful review process, grounded in the clinical value demonstrated in the CARES-310 study," said Kim Dong-geon, CEO of Elevar Therapeutics.
With the facility inspections resolved and the resubmission filed, the momentum for HLB’s liver cancer treatment has been restored. Once the FDA confirms the review classification, the timeline will become clearer, potentially accelerating HLB’s global oncology business expansion should the drug receive U.S. approval.
