Korea Biomedical Review is publishing a series of articles to analyze the top 10 Korean pharmaceutical and biopharma companies with the largest market capitalizations listed on the main bourse, Kospi, and the tech-heavy Kosdaq. The series aims to reflect key industrial issues and the flow of the capital market in the Korean pharmaceutical and biopharma industry. This is the eleventh installment. -- Ed.

HLB has been preparing for four years to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for rivoceranib, which the company says is a promising candidate for cancer treatment.

Initially developed to treat gastric cancer, rivoceranib faced a setback during the NDA submission for this indication. Since then, HLB has expanded the drug's targeted indications and is currently testing it in combination with various drugs.

HLB's latest goal is to submit an NDA to the FDA for using a combination therapy of rivoceranib and camrelizumab, an immune anticancer drug from Jiangsu Hengrui Pharmaceutical, as the first-line treatment for hepatocellular carcinoma (HCC).

This will be an important milestone for the company as it has yet to succeed in filing an NDA for rivoceranib, despite its efforts to apply an NDA to treating gastric and adenocarcinoma.

In 2019, HLB announced its plan to submit an NDA to the FDA for rivoceranib as a third-line treatment for gastric cancer by 2020.

HLB's decision to file an NDA for rivoceranib as a third-line treatment for gastric cancer was based on the drug's superior progression-free survival (PEF) compared to the control group, even though it did not achieve the primary clinical outcome of overall survival (OS).

However, the NDA application for rivoceranib for gastric cancer was delayed after the FDA required the company to supplement the data.

Although HLB received external data from Jiangsu Hengrui Pharmaceutical last year and completed the supplemental data required by the FDA, there has been no progress in submitting the NDA for rivoceranib as a treatment for gastric cancer.

Since the delay of the first NDA, HLB has conducted clinical trials of rivoceranib in various cancers, including adenocarcinoma, HCC, colorectal cancer, and lung cancer.

HLB planned to file one NDA for either HCC or adenocarcinoma last year, but the deadline was pushed back to this year.

Until the second half of last year, HLB expected that the NDA for adenocarcinoma would be the fastest.

However, after another request for additional data from the FDA, the company decided to file NDA for HCC first.

The company is currently expected to submit an NDA for combo therapy of rivoceranib and camrelizumab to treat HCC to the FDA in May.

Rivoceranib the first angiogenesis inhibitor (VEGF TKI) and camrelizumab is an immune checkpoint inhibitor (PD-1 inhibitor). 

In phase 3 clinical trials, the median overall survival (mOS) was 22.1 months in HCC patients treated with the combo therapy, versus 15.2 months in the control group treated with sorafenib. The median progression-free survival (mPFS) was 5.6 months vs. 3.7 months, and the ORR (objective response rate) was 25.4 percent vs. 5.9 percent.

Notably, the combo has confirmed high efficacy in patients infected with HBV (hepatitis B virus) as well as HCV (hepatitis C virus), the leading cause of liver cancer in Western countries, and in non-viral patients, confirming its broad therapeutic efficacy regardless of ethnicity or cause. 

HLB's future looks bright for now

HLB's progress on submitting an NDA for the combination therapy of rivoceranib and camrelizumab as a primary treatment for HCC is now on track.

According to the company, the FDA has given a go-ahead with HLB's NDA for the rivoceranib combination therapy through a pre-NDA consultation.

HLB Chairman Jin Yang-gon told Korea Biomedical Review that it was “almost certain” that the company would submit the NDA in May.

“We're monitoring the situation every day, and the process is going to be smooth,” Jin said during HLB Bio Forum 2023 in Songdo on Thursday. 

Local analysts have expressed a positive outlook.

Wi Hae-ju, a researcher at Korea Investment & Securities, said rivoceranib will need regulatory flexibility from the FDA to receive approval in the U.S. successfully.

"The FDA approval of China's Junxi Biosciences' toripalimab provides a preview of the potential for HLB and Hangxu Pharmaceutical to enter the U.S. amid the ongoing U.S.-China dispute," she said. "The FDA also mentioned the need to exercise regulatory flexibility in rare cancers such as nasopharyngeal carcinoma and HCC, which is important for the company as it needs regulatory flexibility for the FDA to recognize a combination therapy as a single new drug."

Wi's comment refers to the fact that both rivoceranib and camrelizumab have not been approved by the FDA separately and that there are currently no cases where the FDA approved a combination therapy that uses drugs unapproved by the agency.

HLB completes transformation into a full-fledged biocompany

Meanwhile, HLB is investing heavily in the commercialization of rivoceranib in the U.S. and is shifting its business structure to focus on biotechnology.

HLB announced that it has successfully completed the spinoff of its shipping business and transitioned to a biotech company on April 20.

The company will complete the spinoff by May 19, and the company expects that it will be able to attract capital from global healthcare funds.

Last year, the company also secured 240 billion won ($179.5 million) through a capital increase and decided to invest about 70 percent of it in its U.S. subsidiary to promote rivoceranib if it receives approval.

HLB's 2022 earnings have garnered the attention of investors thanks to the swing in operating profit to a positive figure.

HLB posted 176.69 billion won sales in 2022, up 384 percent from 2021, and 37.65 billion won in operating profit.

While HLB's positive indicators, including the swing in operating profit and progress on the HCC NDA, are promising, the outcome of the NDA submission to the FDA in May will be crucial to sustain these positive trends. As the company's shares have been declining since April 14, investors will be closely watching the outcome of the NDA submission to determine the future trajectory of HLB.

As of 10:17 a.m. Thursday, the company's shares stood at 34,100 won, up 0.29 percent from the previous day.