HLB(028300) received a complete response letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its new drug application for a liver cancer treatment.
The company said no issues were raised about clinical efficacy or safety during the review, but that the result of a current good manufacturing practice (cGMP) inspection of the manufacturing site of its co-developer, China's Jiangsu Hengrui Pharmaceuticals, became a stumbling block.
HLB said on the 10th that its U.S. subsidiary Elevar Therapeutics received a CRL from the FDA on the 9th (local time) for the Rivoceranib new drug application (NDA).
HLB has been seeking FDA approval for a combination therapy of Rivoceranib and Jiangsu Hengrui Pharmaceuticals' "Camrelizumab."
But all three attempts were halted.
According to the company, the FDA said in the CRL that observations were identified during a general cGMP inspection of a Hengrui manufacturing facility listed in the Rivoceranib NDA, resulting in the issuance of a Form 483. A Form 483 is a document the FDA uses to notify a firm of conditions that may constitute violations observed during an inspection.
The FDA said the observations may not be directly related to the Rivoceranib application itself, but because the facility is included in the NDA, the site must remediate them in a timely manner. It also specified that Rivoceranib cannot be approved until compliance with cGMP at the facility is verified.
The FDA added that even after the cGMP issues are resolved, it can conduct a pre-approval inspection (PAI) of the facility if needed, and that both the cGMP inspection and the PAI must be satisfactory for final approval.
The facility in question underwent a general cGMP inspection by the FDA in April and received a Form 483, and follow-up remediation is underway. The final inspection classification has not yet been determined.
According to the company, this facility was inspected by the FDA for the first time in about eight years since 2018; in the five prior inspections, it received four "no action indicated (NAI)" and one "voluntary action indicated (VAI)" classifications.
HLB said Elevar and HLB were not informed in advance about the issuance of the Form 483 because this inspection was a routine general cGMP inspection, not a pre-approval inspection (PAI) for the application review.
Elevar, immediately after receiving the CRL, formally requested from Hengrui the Form 483, the responses submitted to the FDA, and the remediation timeline, and plans to review the materials and work with the FDA to pursue resubmission.
Kim Dong-geon, CEO of Elevar, said, "This CRL did not include any observations on clinical efficacy or safety data, nor any requests for additional clinical trials," adding, "We will promptly address the cGMP issues at the manufacturing facility and resubmit as soon as possible."