Two manufacturing facilities completed re-application for FDA VAI determination and approval
3-year survival rate 37.7%... Expect new drugs for liver cancer following Repick2
HLB (028300) is preparing for a new leap forward in the U.S. anticancer drug market by completing the reapplication for approval from the U.S. Food and Drug Administration (FDA) for a new liver cancer drug. Quality control issues at two Chinese manufacturing facilities that had blocked approval in the previous review were corrected and follow-up inspections were completed, making it possible for a long-planned liver cancer new drug to enter the U.S. market again.
This re-application has greater significance for HLB Group, which secured FDA approval for the bile duct cancer treatment ‘Repick2’ last month. If a new liver cancer drug is approved, the United States will have two new anticancer drugs targeting different types of cancer. Expectations for a reevaluation of corporate value are also rising as the company can move from waiting for approval for a single new drug to expanding its global business based on multiple anticancer drugs.
HLB announced through a voluntary disclosure on the 12th that its U.S. subsidiary Elevar Therapeutics resubmitted an application to the FDA on the 9th (local time) for approval of the combination therapy of riboceranib and camrelizumab as a first-line treatment for liver cancer. Rivoceranib is subject to a New Drug Application (NDA), and camrelizumab is subject to a Biopharmaceutical License Application (BLA).
[Source: Financial Supervisory Service Electronic Disclosure System (DART), HLB liver cancer new drug FDA approval re-application announcement]
VAI decision at two manufacturing facilities… Official letter from FDA states lifting alert
What is noteworthy in this reapplication is the results of the FDA's follow-up inspection of the Hengseo Pharmaceutical manufacturing facility in China. As requests for supplementation related to manufacturing and quality control were raised in the previous permit review, the completion of inspections of the two facilities is a meaningful step forward in resuming the permit process.
Hengxi Pharmaceutical's Jinqiao raw drug manufacturing facility was assessed as VAI during an FDA inspection. An official letter issued by the FDA on July 22 stated that the inspection results of the facility were classified as VAI, and the existing Potential Subject to Official Action (pOAI) alert was lifted. The FDA also notified that the facility was judged to be in acceptable condition according to current Good Manufacturing Practices (cGMP).
In an official announcement last July, Hengseo Pharmaceutical stated, “FDA’s request for supplementation is not related to clinical trial data or safety/efficacy issues.”
[Source: U.S. FDA official letter, Hengshe Pharmaceutical Jinqiao manufacturing facility VAI determination/pOAI alert lifted]
VAI is a classification given when improvements are identified during the inspection process, but it is determined that the company can respond through voluntary correction without formal regulatory action from the FDA. Although this result shows that concerns related to quality control at manufacturing facilities have been alleviated, it does not mean final product approval for individual drugs.
The Dongjin facility, which produces finished drugs of Rivoceranib, also received VAI recognition from the FDA. HLB announced on the 6th that Hangseo Pharmaceutical had been notified of the completion of the inspection of the facility, and Elevar completed the supplementary procedures for the two manufacturing facilities and then re-applied for this license.
[Source: HLB official blog, announcement regarding FDA VAI decision at Dongjin manufacturing facility of Hengseo Pharmaceutical]
Clinical results published in Lancet Oncology… 3-year survival rate 37.7%
The combination therapy of rivoceranib and camrelizumab achieved the result of significantly increasing survival time compared to existing treatments in the global phase 3 clinical trial CARES-310. The final analysis results were published in the international academic journal ‘The Lancet Oncology’ in December last year.
In a clinical trial involving 543 patients, the median overall survival time for combination therapy was 23.8 months, which was 8.6 months longer than the 15.2 months for the existing treatment sorafenib. The risk of death during the clinical follow-up period was also found to be 36% lower than that of the comparison group.
There were also clear differences in long-term survival rates and tumor responses. The three-year survival rate was 37.7%, which was 12.9% higher than sorafenib's 24.8%, and the objective response rate (ORR), which is the percentage of patients whose tumor size was reduced by a certain standard, was 26.8%, more than four times higher than the 5.9% of existing treatments.
In terms of safety, the incidence of some adverse reactions, such as hypertension, in the combination therapy group was higher than that in the comparison group. By combining the efficacy and safety results, the researchers suggested the possibility that the combination therapy could become a new primary treatment option for advanced liver cancer.
In addition to confirming the extended survival period and high tumor response rate compared to existing treatments, the FDA approval process for entry into the U.S. market was restarted by correcting the manufacturing and quality control issues pointed out in the previous review.
From Repick To to liver cancer... Challenge of two types of new anticancer drugs system in the U.S.
Last September, HLB Group secured FDA approval for the bile duct cancer treatment Lipictu (ingredient name: rirafugratinib) through its U.S. subsidiary Eleva. The current approved indication is FGFR2 fusion or rearrangement-positive advanced cholangiocarcinoma with existing treatment experience. Separately, Elevar is pursuing phase 2 clinical trials targeting patients with other advanced solid tumors, and is also working on the development of a ‘carcinoma-agnostic’ drug that targets multiple cancer types based on specific genetic mutations.
While Lipic2 is expanding its treatment area to other solid cancers, the rivoceranib/camrelizumab combination therapy targets the primary liver cancer treatment market, which has a relatively large patient population. If a new liver cancer drug receives FDA approval, HLB Group will have the foundation to pursue commercialization of anticancer drugs in different cancer types.
In the domestic pharmaceutical industry, which has a history of about 130 years since the establishment of Dongwha Pharmaceutical in 1897, the approval of a new anti-cancer drug by the U.S. FDA is considered an important milestone in entering the global market. If HLB Group receives approval for a new drug for liver cancer, it could also attract attention as an example of a domestic bio company expanding its business base in the U.S. anticancer drug market.
In evaluating corporate value, the importance of not only clinical results and approval possibilities but also actual sales performance may increase. HLB Group's mid- to long-term performance and business value may vary depending on the extent to which RepickTwo's indications are expanded and the commercialization of liver cancer new drugs is successful.
HLB showed high stock price volatility, including concentrated short selling after RepickTwo was approved. As the FDA approval of a liver cancer new drug can affect investment sentiment and market supply and demand, this reapplication is an important process that will determine not only the performance of new drug development but also market evaluation.
The FDA's reexamination type and schedule will vary depending on manufacturing and quality control-related supplements and how existing inspection results are reflected in the review. Once the FDA sets the reexamination type and target schedule, the next schedule for evaluating approval is expected to become concrete.
By completing the VAI decision for the two manufacturing facilities and re-applying for approval, HLB Group has laid the foundation for re-entering the U.S. market for a new drug for liver cancer. The market's attention is focused on whether FDA approval of the second new anticancer drug following RepickTwo can be realized and whether this review will serve as an opportunity to take HLB's U.S. anticancer drug business to the next level.
