HLB, Having Surpassed Cholangiocarcinoma, Expected to Resubmit New Liver Cancer Drug Application to FDA Next Month

Received Three Complete Response Letters Despite Phase 3 Success
Focus on the Appropriateness of Phase 3 Comparison with Former Standard of Care

Market attention is focused on whether HLB, which obtained approval from the U.S. Food and Drug Administration (FDA) for its cholangiocarcinoma treatment LePikto (ingredient name: lirafugratinib), will also succeed in securing approval for its key pipeline, a new liver cancer drug. If HLB receives approval for the new liver cancer treatment, the company will then have two anti-cancer drugs approved for direct sale in the U.S. With the pathway opened by the cholangiocarcinoma treatment, HLB would have a “two-stage leap” by scaling up with the liver cancer drug.

According to industry sources on September 29, HLB is likely to resubmit its application for approval to the FDA as early as next month for the combination therapy of rivoceranib and camrelizumab as a new liver cancer drug. The results of the finished drug manufacturing site inspection, completed in early July, are expected later this month. Once the inspection results are released, HLB plans to immediately proceed with resubmission procedures unless there are any special circumstances.

The combination therapy of rivoceranib and camrelizumab received its third Complete Response Letter (CRL) from the FDA in July. Deficiencies were found during a routine inspection of the rivoceranib manufacturing facility in China operated by Hengrui Pharma. The manufacturing issue was concluded in the same month when the FDA issued a Voluntary Action Indicated (VAI) status. In its letter, the FDA stated that this finding would not directly disadvantage the pending approval review. Preparation of the latest safety data, which will be included in the resubmission documents, is in its final stages. The data required by the FDA includes results from ongoing combination clinical trials and post-market data from China.

Manufacturing Site Issues Concluded; The Core Question Now Is the Clinical Control Group for the Liver Cancer Drug

The combination therapy of rivoceranib and camrelizumab emphasizes improved survival times as its strength. In phase 3 clinical trials involving 543 participants, the median overall survival was 23.8 months, which is 8.6 months longer than the control group (sorafenib, 15.2 months). The median progression-free survival was also 5.6 months, surpassing sorafenib (3.7 months). The comparison drug, sorafenib, is Bayer’s “Nexavar,” which received FDA approval in 2007.

There are observations that one of the key points of FDA review may be the appropriateness of sorafenib as the control group in the clinical trial. A university hospital oncology professor commented, “The critical question is whether results comparing the drug to sorafenib, the previous standard of care, will be accepted as valid evidence for current American patients.” When the trial began in 2019, sorafenib was the standard of care, but today, first-line liver cancer treatment is led by immune checkpoint inhibitor combinations such as Roche’s Tecentriq and Avastin.

In 2022, the FDA declined approval for Eli Lilly’s lung cancer immunotherapy sintilimab because the pivotal clinical trial was conducted solely in China, and the comparison drug was not the standard-of-care treatment in the U.S. In contrast, the combination therapy with rivoceranib and camrelizumab was a global clinical study, and so far, all publicized CRL reasons have been related to manufacturing. Nevertheless, the choice of control group could still become an issue during the review process.

The liver cancer market, for which HLB now aims to secure FDA approval, is significantly larger than the cholangiocarcinoma market. According to market research firm MarketGlass, the U.S. hepatocellular carcinoma treatment market targeted by the rivoceranib and camrelizumab combination was estimated at 560.3 million dollars (approximately 766 billion won) last year. This is about 2.5 times the size of the U.S. cholangiocarcinoma treatment market (227.1 million dollars) as calculated in the same survey. Looking globally, the unresectable hepatocellular carcinoma market exceeds 1.8 billion dollars (about 2.461 trillion won), more than twice the cholangiocarcinoma market (776.1 million dollars).

This content was produced with the assistance of AI translation services.