HLB’s Liver Cancer Drug Fails FDA Approval Again: “Hansoh Pharma cGMP Inspection Issue”

Receipt of Complete Response Letter Regarding Hansoh Pharma Manufacturing Facility

HLB’s liver cancer drug candidate ‘Rivoceranib’ has once again failed to clear the U.S. Food and Drug Administration (FDA) hurdle. The company received a Complete Response Letter (CRL), which pointed out issues related to the current Good Manufacturing Practice (cGMP) at the manufacturing facility of Hansoh Pharma, its Chinese partner. HLB stated that it plans to refile its application as soon as the relevant documentation is secured.

HLB announced on July 10 that its U.S. subsidiary, Elevar Therapeutics, had received a CRL from the FDA regarding the New Drug Application (NDA) for Rivoceranib on July 9 (local time).

The CRL stated that, during the cGMP inspection of the Hansoh Pharma manufacturing facility listed in the Rivoceranib NDA, certain deficiencies were identified and a Form 483 (a document notifying the company of inspectional observations) was issued. The FDA explained that although the observations from this inspection may not relate directly to the NDA for Rivoceranib itself, since the facility is listed in the NDA, the issues must be addressed in a timely manner in collaboration with the manufacturer.

The FDA made it clear that the NDA for Rivoceranib cannot be approved until the deficiencies at the manufacturing facility are resolved and compliance with cGMP is confirmed. Furthermore, the CRL noted that, even after issues related to cGMP are resolved, the FDA may conduct a Pre-Approval Inspection (PAI) of the facility if necessary, and approval will only be granted if both the cGMP inspection and the PAI yield satisfactory results.

The facility in question has been taking follow-up actions since receiving a Form 483 after cGMP inspection by the FDA in April, but the final classification of the inspection results has yet to be determined. This inspection was the first in about eight years since 2018, and during the previous five FDA routine inspections, the facility received a “No Action Indicated (NAI)” rating four times and a “Voluntary Action Indicated (VAI)” rating once.

Rivoceranib is a key pipeline for HLB’s entry into the global anticancer drug market. Combination therapy with this compound and the immuno-oncology agent Camrelizumab (an immune checkpoint inhibitor developed by Hansoh Pharma) has been developed as a first-line treatment for hepatocellular carcinoma. The combination therapy previously faced approval delays in FDA review due to manufacturing issues with Camrelizumab. In the 2024 CRL issued by the FDA, problems were cited regarding Hansoh Pharma’s compliance with pharmaceutical manufacturing and quality standards (GMP), as well as delays in clinical site inspections. Manufacturing-related deficiencies were also raised last year. With the receipt of this additional CRL, HLB once again exposed chemistry, manufacturing, and controls (CMC) issues in the global approval process, regardless of the clinical efficacy of its candidate.

The company explained that the inspection underlying this CRL was a routine cGMP inspection of the Hansoh Pharma facility, not a Pre-Approval Inspection (PAI) for approval review. Therefore, HLB and Elevar were not informed in advance about the inspection or the issuance of Form 483. After receiving the CRL, Elevar confirmed that the inspection was indeed relevant to the drug approval review and has officially requested Hansoh Pharma to provide Form 483, the corresponding responses, and information on when remediation is expected to be completed.

HLB plans to thoroughly analyze the FDA Form 483 and Hansoh Pharma’s remediation documentation and to announce a concrete response plan for rapid resubmission after close consultation with Hansoh Pharma.

Donggun Kim, CEO of Elevar, stated, “No observations or additional clinical trial requirements were identified in the CRL regarding clinical efficacy or safety data. Since the main deficiencies are related to the cGMP inspection of the manufacturing facility, we will work closely with the FDA to clarify the necessary procedures and pursue resubmission as quickly as possible.”

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