Doctors long for a new treatment option for liver cancer

Demands improvement of reimbursement standards for Tecentriq+Avastin

After HLB’s rivoceranib fails to receive approval… ImmuneOncia gains the spotlight for developing second-line treatment

Progressive hepatocellular carcinoma, or liver cancer, is a disease with only a few effective treatment options in the clinical setting.

 

Recently, the emergence of various first-line treatment options such as targeted anticancer drugs and immuno-oncology drugs, has raised expectations for improved treatment outcomes.

 

However, treatment options for liver cancer are still in high demand in the clinical setting due to low treatment response rates, the lack of biomarkers for treatment selection, and the lack of second-line treatment options.

 

# Among these, the domestic pharmaceutical and bio industry is attracting attention, with Korean companies making a bid into the global big pharma-led drug market with their development of new drugs.

 

According to the medical community on the 7th, the treatment options that are used as a standard therapy in the first-line treatment of liver cancer are the Tecentriq (atezolizumab) and Avastin (bevacizumab) combination therapy.

 

According to the “Guidelines for the Treatment of Hepatocellular Carcinoma” revised by the Korean Liver Cancer Association and the National Cancer Center in 2022, if a liver cancer patient is not indicated for surgery or local treatment as first-line systemic therapy, the Tecentriq and Avastin combination or Imfinzi (durvalumab) and Imjudo (tremelimumab) is recommended as the first choice.

 

Professor Hong-Jae Jeon of the CHA Bundang Medical Center (Hematolo-oncology), explained, “Liver cancer is the sixth most common cancer worldwide and the second leading cause of cancer deaths in Korea, and various treatment options have emerged to improve its prognosis.

 

However, there is still a high unmet need in terms of long-term survival.

 

As the development of therapeutic agents continues with the aim of improving the treatment outcomes of liver cancer, immune-oncology drugs have recently emerged as an innovative first-line treatment option for liver cancer.’ However, the standard therapy currently available for practical use in clinical practice is limited to the Tecentiq+Avastin combination.

 

Previously, there were treatments such as Nexavar (sorafenib) and Lenvima (lenvatinib), but in the course of developing treatments, the Tecqntriq+Avastin combination has recently been used as a standard therapy.

 

In the case of the Imfinzi+Imjudo combination, which has improved the risk of bleeding, a typical side effect of existing treatments, the combination has been approved by the Ministry of Food and Drug Safety in Korea but is not reimbursed by the National Health Insurance, so it can only be used as a non-reimbursed drug.

 

AstraZeneca, Imfinzi’s developer, pushed for reimbursement and passed the threshold of the Cancer Disease Review Committee of the Health Insurance Review and Assessment Service in November last year, but the application is still in the pharmacoeconomic evaluation stage of the subcommittee under the Drug Reimbursement Evaluation Committee.

 

Imjudo, which is used in combination with Imfinzi, is administered only once, but the patient must pay KRW 10 million for the single shot, so it is essential for the company to apply for the combination’s reimbursement due to poor patient access in terms of finances.

 

As a result, although there are currently 4 liver cancer treatment options approved in Korea, the first-line treatment option is limited to the Tecentriq+Avastin combination.

 

The problem is that the reimbursement of even this combination is at risk of being cut back in the field.

 

In fact, major medical associations have prepared and submitted a proposal to the Health Insurance Review and Assessment Service to improve reimbursement standards for liver cancer treatments, led by the Tecentiq+Avastin combination, in the second half of last year.

 

This is believed to be a measure to reduce the frequency of reimbursement price cuts due to increased claims for this treatment option.

 

Professor Hyun Yang of Eunpyeong St.

 

Mary's Hospital (Department of Gastroenterology) recently gave a presentation on the topic at the Korean Liver Cancer Association.

 

He said, “There is a gap between the actual reality and the application of reimbursement for systemic treatment of hepatocellular carcinoma.

 

There is ambiguity in the reimbursement criteria for the Tecentriq+Avastin combination therapy, which states 'local treatment is not possible,’ and there is a gap between the indication for the Phase III clinical trial of the Imfinzi+Imjudo combination therapy as well as the combination therapy in question.” Soon Sun Kim, Insurance Director of the Korean Liver Cancer Association (Department of Gastroenterology, Ajou University Hospital), said, “We submitted expert consensus opinions to HIRA on the reimbursement application of systemic liver cancer treatment for hepatocellular carcinoma.

 

We presented the opinion paper to improve the ambiguity of the reimbursement criteria for the use of such treatments.” The lack of treatment options for liver cancer in clinical settings has created an unmet demand, and the domestic pharmaceutical and biotechnology industries, which have identified the marketability in the field, are busy developing new drugs.

 

A typical example is HLB's rivoceranib.

 

HLB Life Science acquired the development rights to rivoceranib from Bukwang Pharm in 2018 for KRW 40 billion.

 

Since then, HLB has been developing a combination therapy of lenvatinib and camrelizumab for liver cancer with Jiangsu Hengrui Pharmaceuticals Company, Camrelizumab, which was developed by Jiangsu Hengrui Pharmaceuticals Company, is an immuno-oncology drug that inhibits the PD-1 protein expressed on the surface of immune cells (T cells), preventing them from binding to the PD-L1 receptor on the surface of cancer cells and activating immune cells.

 

According to the results of the Phase III CARES-310 study, which was unveiled at the 2022 European Society for Medical Oncology (ESMO) by HLB and Jiangsu Hengrui Pharmaceuticals, the combination of rivoceranib and camrelizumab recorded a median overall survival (OS) of 22.1 months, an improvement over Nexavar’s 15.4 months.

 

However, the FDA approval was again denied last month, following the one in May last year.

 

As with the previous time, the issue this time is also related to the Chemistry, Manufacturing, and Control (CMC) of camrelizumab by Jiangsu Hengrui Pharmaceuticals.

 

However, HLB has expressed its intention to reapply for FDA approval, so there is still a possibility of approval.

 

The progress of Yuhan Corporation's subsidiary, ImmuneOncia, a biotech company specializing in immuno-oncology drugs, is also noteworthy.

 

The company's pipeline has recently attracted increased attention after passing the preliminary screening for the KOSDAQ listing.

 

In particular, there is a lot of interest in 'IMC-002’ in the company's pipeline of monoclonal antibodies targeting the CD47 factor.

 

MC-002 is an immune checkpoint inhibitor for macrophages that blocks the “don't eat me” signal between CD47 on cancer cells and SIRPα on macrophages, helping macrophages attack cancer cells (phagocytosis).

 

In Phase Ia clinical trial on solid tumors, it has been attracting attention as a CD47 immuno-oncology drug candidate that global big pharma has given up on because it minimizes binding to normal cells such as red blood cells and is highly safe.

 

Based on this, ImmuneOncia also signed a technology export contract for IMC-002 to China with 3D Medicines for KRW 540 billion in 2021.

 

The results of the Phase Ib clinical trial of IMC-002 will be presented at the American Society of Clinical Oncology (ASCO 2025) congress scheduled to be held in May.

 

ImmuneOncia plans to develop IMC-002 as a second-line treatment option for liver cancer, which has a high unmet clinical need.

 

“The biggest feature is that it binds strongly to cancer cells while minimizing binding to normal cells, such as red blood cells,” said Heung Tae Kim, CEO of ImmuneOncia (Oncology specialist).

 

”This is why global pharmaceutical companies have been held back.

 

Existing candidate substances had a strong tendency to bind with red blood cells, causing side effects such as anemia and thrombocytopenia, but IMC-002 has solved the safety issues and is expected to be highly effective,” he explained.

 

Kim added, ”In addition to the safety data, we will present efficacy data on our candidate at ASCO 2025.

 

While our competitors have been developing treatments for blood cancers, we are currently conducting clinical trials for liver cancer among solid cancers.

 

In the case of liver cancer, there are first-line treatment options regarded as standard of care, but there are virtually no therapies available as a second-line treatment.

 

We are working to provide next-generation options in this market.”