Raw material and finished product manufacturing facilities receive VAI judgment one after another… Reapply after 3 months
Phase 3 clinical trial survival period of 23.8 months, death risk reduced by 36%... U.S. approval review schedule to be confirmed
HLB (028300) has completed re-application for new drug approval from the U.S. Food and Drug Administration (FDA) for the combination therapy of rivoceranib and camrelizumab, which is being developed as a first-line treatment for liver cancer. As raw material and finished drug manufacturing facilities have received the FDA's Voluntary Corrective Action Advisory (VAI) decision one after another, the inspection of the production facility, which was the cause of the approval delay, has also been completed. HLB is seeking to enter the U.S. market again based on the survival time improvement effect confirmed in the global phase 3 clinical trial.
HLB announced on the 12th that its U.S. subsidiary Elevar Therapeutics and Chinese partner Hengrui Pharma submitted a new drug application (NDA/BLA) for riboceranib and camrelizumab combination therapy to the FDA on the 9th (local time).
This reapplication comes about three months after receiving the FDA's supplementation request letter (CRL) in July. Eleva and Hengseo Pharmaceutical have since been working on supplementing their manufacturing facilities, and recently began re-applying as all FDA inspections of raw material and finished drug manufacturing facilities were concluded with VAI.
Both raw material and finished product manufacturing facilities are VAI… Securing a basis for permit re-application
Manufacturing and quality control issues were raised as major supplementary issues in the previous approval review for HLB's liver cancer new drug. In 2024 and 2025, camrelizumab manufacturing and quality control (CMC) issues, and in July of this year, the results of the pharmaceutical manufacturing and quality management (cGMP) inspection of the riboseranib raw drug manufacturing facility affected the approval schedule.
Last July, the Rivoceranib drug substance (DS) manufacturing facility received a VAI judgment from the FDA, and Hengseo Pharmaceutical submitted a corrective and preventive action (CAPA) regarding the issues pointed out by the finished drug product (DP) manufacturing facility.
Earlier this month, a finished pharmaceutical manufacturing facility also received VAI recognition. HLB announced on the 6th that the FDA classified the facility's regular cGMP inspection as VAI, and on the 3rd, Eleva received a letter from Hengseo Pharmaceutical to terminate the inspection.
VAI applies to cases where some improvements have been identified during an inspection of a manufacturing facility, but the FDA has determined that immediate formal regulatory action is not necessary. The related inspection was completed with both raw materials and finished product manufacturing facilities receiving VAI recognition, and Eleva and Hangseo Pharmaceutical submitted re-application documents after consultation with the FDA.
At the time of the CRL last July, HLB explained that there were no new comments or requests for additional clinical trials regarding clinical efficacy or safety. This time, the company applied for approval based on the results of the global phase 3 clinical trial CARES-310.
Survival period: 23.8 months... Reconfirmation of global phase 3 clinical trial results
In the final analysis of CARES-310, the median overall survival (mOS) of the riboseranib/camrelizumab combination therapy was 23.8 months, which was 8.6 months longer than the 15.2 months of the control group, sorafenib. The risk of death was 36% lower than the control group (HR 0.64, 95% confidence interval 0.52-0.79).
HLB explained that the survival period is the longest among clinical results for primary treatment of liver cancer reported to date. Although it is difficult to directly compare different clinical trials, the company evaluates that the results show its competitiveness compared to existing treatments.
The final analysis results of CARES-310 were published in the international academic journal ‘The Lancet Oncology’ in December last year. According to the company, the combination therapy was presented as a first-line treatment option for liver cancer in the 2025 Barcelona Liver Cancer Clinic (BCLC) treatment strategy and the European Society of Medical Oncology (ESMO) guidelines.
FDA review schedule to be confirmed… Following bile duct cancer, liver cancer approval is being promoted.
After the FDA officially receives the reapplication documents, it determines the type of review based on the scope of the supplementary materials and the need for review. A review period of 2 months applies to Class 1 and 6 months to Class 2, and the type of application and target date for approval decision have not yet been confirmed.
After securing FDA approval for bile duct cancer treatment rirafugratinib last September, HLB has again sought approval for the first-line liver cancer treatment. If a new drug for bile duct cancer and a combination therapy for liver cancer are approved, the product portfolio can be expanded in the U.S. anticancer drug market.
Kim Dong-gun, CEO of Eleva Therapeutics, said, “Now that the manufacturing facility inspection process has been completed, we will work closely with the FDA to successfully complete this approval review based on the clinical value confirmed in CARES-310.”
As the inspection evaluation of the raw material and finished product manufacturing facilities was completed and the FDA re-application was completed, the approval schedule for HLB's liver cancer new drug began to move again. Once the FDA's review type is confirmed, the future schedule will become more concrete, and if US approval is secured for liver cancer treatments following bile duct cancer, the expansion of the global anticancer drug business is expected to accelerate.
