Manufacturing Facilities Cleared by FDA with VAI Status; Re-application Finalized
3-Year Survival Rate at 37.7%... Hopes Rise for Liver Cancer Drug Following Rivfloza Approval
HLB (028300) is preparing for a new phase in the US oncology market after completing the resubmission of its liver cancer treatment to the US Food and Drug Administration (FDA). With the quality control issues at two Chinese manufacturing facilities—which stalled the previous application—now addressed and subsequent inspections concluded, the company’s long-standing push to enter the US market for liver cancer treatment is back on track.
This resubmission holds significant weight for the HLB Group, which secured FDA approval for its biliary tract cancer treatment, "Rivfloza," just last month. Should the liver cancer drug receive the green light, HLB would command a portfolio of two distinct oncology therapies in the US. This transition from a single-drug applicant to a multi-drug operator is fueling market expectations for a significant corporate valuation re-rating.
In a regulatory filing on the 12th, HLB announced that its US subsidiary, Elevar Therapeutics, resubmitted the application for the combination therapy of Rivoceranib and Camrelizumab as a first-line treatment for liver cancer on the 9th (local time). Rivoceranib is being filed under a New Drug Application (NDA), while Camrelizumab is submitted via a Biologics License Application (BLA).
[Source: Data Analysis, Retrieval and Transfer System (DART), HLB FDA Resubmission Filing]
Manufacturing Sites Receive VAI Status; FDA Official Letter Confirms Warning Lifted
A key highlight of this resubmission is the outcome of the FDA's follow-up inspections of the Hengrui Pharma manufacturing facilities in China. As previous regulatory hurdles were centered on manufacturing and quality control, the completion of these inspections represents a critical breakthrough.
The FDA classified Hengrui Pharma’s Jinqiao API (Active Pharmaceutical Ingredient) manufacturing facility as Voluntary Action Indicated (VAI). An official FDA letter dated July 22 confirmed this VAI status and explicitly stated that the prior "potential Official Action Indicated" (pOAI) warning had been lifted. The FDA further communicated that the facility is considered acceptable under current Good Manufacturing Practice (cGMP) standards.
Hengrui Pharma previously stated in a July announcement that the FDA’s original requests for clarification were unrelated to clinical data, safety, or efficacy issues.
[Source: Official FDA Letter, Hengrui Pharma Jinqiao Facility VAI Status and pOAI Warning Removal]
A VAI designation indicates that while some improvements were identified during inspections, they do not necessitate formal FDA regulatory action and can be addressed through the company's voluntary corrections. While this signals a mitigation of quality control concerns, it does not constitute final product approval.
The Dongjin facility, which manufactures the finished Rivoceranib drug product, also received VAI status. HLB announced on the 6th that Hengrui Pharma had been notified of the completion of that inspection, and Elevar proceeded with the resubmission only after completing the remediation processes for both facilities.
[Source: HLB Official Blog, Announcement on Hengrui Pharma Dongjin Facility FDA VAI Status]
Clinical Milestones Published in The Lancet Oncology: 3-Year Survival Rate of 37.7%
The combination therapy of Rivoceranib and Camrelizumab previously demonstrated superior survival outcomes compared to existing therapies in the global Phase 3 "CARES-310" clinical trial. Final analysis results were published in the international medical journal *The Lancet Oncology* last December.
In a trial involving 543 patients, the median overall survival (OS) for the combination therapy was 23.8 months, significantly outperforming the 15.2 months seen with the standard-of-care drug, Sorafenib. The risk of death was 36% lower in the combination group compared to the control group.
The study also showed marked improvements in long-term survival and tumor response. The 3-year survival rate was 37.7%, 12.9 percentage points higher than the 24.8% observed with Sorafenib. The Objective Response Rate (ORR)—the percentage of patients whose tumor size decreased by a defined threshold—was 26.8%, more than four times higher than the 5.9% observed in the control group.
While the safety profile showed higher incidences of certain adverse events, such as hypertension, in the combination group, researchers concluded that the therapy offers a compelling new first-line treatment option for patients with advanced liver cancer.
Having addressed the quality control issues identified in the initial review, and with clinical efficacy firmly established, the regulatory pathway to the US market has officially reopened.
Beyond Rivfloza: Aiming for a US Oncology Portfolio
In September, the HLB Group secured FDA approval for the biliary tract cancer treatment Rivfloza (generic name: lirafugratinib) through its US subsidiary, Elevar. Currently, the indication is for patients with advanced biliary tract cancer who have previously received treatment and test positive for FGFR2 fusion or rearrangement. Separately, Elevar is conducting Phase 2 trials for other advanced solid tumors, pursuing a "tumor-agnostic" development strategy to target various cancers based on specific genetic mutations.
While Rivfloza expands the company's reach across solid tumors, the Rivoceranib-Camrelizumab combination targets the much larger first-line liver cancer market. Securing FDA approval for the liver cancer drug would provide the HLB Group with a robust commercial foundation across multiple cancer types.
In the 130-year history of the South Korean pharmaceutical industry, an FDA oncology approval remains a critical milestone for global expansion. Should the HLB Group secure approval for its liver cancer treatment, it will serve as a prominent example of a domestic biotech firm successfully scaling its business in the competitive US market.
Moving forward, corporate valuation will increasingly depend on commercial performance rather than just clinical data and regulatory potential. The long-term earnings and business value of the HLB Group will hinge on the commercial trajectory of Rivfloza and the eventual launch of the liver cancer drug.
HLB has seen significant stock price volatility, exacerbated by heavy short-selling activity following the Rivfloza approval. Given that FDA approval for the liver cancer drug remains a major factor for investor sentiment and market liquidity, this resubmission is a pivotal step that will determine the market’s perception of the company.
The timeline and type of FDA review will be determined by how the agency weighs the recent quality control remediation efforts. Once the FDA classifies the resubmission and sets a target date, a clearer roadmap for the final decision will emerge.
With VAI status secured for both manufacturing sites and the resubmission finalized, the HLB Group has successfully reset its path toward the US liver cancer market. Market observers are now keenly watching to see if a second oncology approval will materialize, potentially serving as a catalyst to propel HLB’s US oncology business to the next level.
