The domestic pharmaceutical company HLB and China's Antengene Corporation's new drug for liver cancer did not receive approval from the U.S. Food and Drug Administration (FDA). They attempted a second FDA approval for commercialization but failed.
According to HLB, the FDA sent a complete response letter (CRL) on the 20th (local time) regarding the review results for the approval of HLB's liver cancer new drug, riboceranib, and the combination therapy of Antengene's camrelizumab as a first-line treatment for liver cancer. The FDA did not disclose the reasons for the lack of approval.
Jin Yang-gon, chairman of HLB, said through YouTube on that day, "The first CRL in May last year was for two issues: the manufacturing and quality control (CMC) of camrelizumab, but this CRL is solely because the CMC issues with camrelizumab have not been sufficiently resolved." He explained, "The CRL does not specifically state what the deficiencies are" and added, "Antengene will quickly contact the FDA to identify what specific content needs to be addressed before responding."
Riboceranib is a targeted cancer drug developed by Elevate, a subsidiary of HLB, while camrelizumab is an immune checkpoint inhibitor from Antengene. Immune checkpoint inhibitors prevent cancer cells from disguising as normal cells, allowing them to be attacked by immune cells.
The two companies first knocked on the FDA's door in 2023. They submitted a new drug application (NDA) to the FDA in May 2023, seeking approval for riboceranib and camrelizumab combination therapy as a first-line treatment for liver cancer based on the global Phase 3 clinical trials. Subsequently, the FDA conducted a clinical site inspection (BIMO) at Harbin Hospital, one of the hospitals conducting the trial, and gave a 'no action item (NAI)' declaration in November 2023. NAI indicates passing. The BIMO inspection is an evaluation where FDA inspectors directly visit the clinical sponsor, clinical hospitals, and clinical research organizations (CRO) to verify the reliability of clinical trial data and compliance with regulations.
However, they encountered obstacles last year. The FDA sent a CRL related to manufacturing facilities (CMC) on May 17, 2024, deciding that additional BIMO inspections were necessary. The issues highlighted by the FDA at that time were defects in the production facilities revealed during Antengene's on-site inspection. Additionally, the FDA pointed out that the clinical trials conducted in Russia and Ukraine could not be inspected due to travel restrictions caused by the war. As a result, HLB's stock price plummeted, and the transfer listing on KOSDAQ was postponed significantly.
Afterward, Antengene began to address the issues pointed out by the FDA. The FDA then conducted BIMO inspections of global Phase 3 clinical hospitals from October 28 to November 15, 2024, subsequently receiving an 'NAI' declaration. Typically, the FDA's BIMO inspections are conducted at 2 to 3 hospitals where the clinical trials were performed.
The final hurdle after the BIMO inspection is the CMC evaluation. CMC is the most important checkpoint because it directly influences product approval. The FDA assesses CMC from the perspective that the responsibility for product development, manufacturing, and quality control lies with the developer to ensure consistent therapeutic effects and safety when administered to patients. HLB submitted additional CMC documentation at the end of January this year and has been waiting for the final results.
Chairman Jin Yang-gon said, "Having worked tirelessly over the past 10 months to achieve good results, I believed that this time I would be able to bring happy news to our shareholders, but I am saddened to bring disappointing news once again," and added, "I will not be discouraged and will overcome this well."
Meanwhile, HLB announced that at the 2024 American Society of Clinical Oncology (ASCO) held in Chicago last year, the global Phase 3 results for the combination therapy of riboceranib and camrelizumab recorded a median overall survival (mOS) of 23.8 months. This is 8.6 months longer than the control drug sorafenib, representing the most positive figure among existing first-line treatments for liver cancer.
Amed Omar Kaseb, a professor at the University of Texas MD Anderson Cancer Center, who participated in the Phase 3 study, said, "The global Phase 3 trial combining riboceranib and camrelizumab has demonstrated the longest patient survival duration in the field of liver cancer therapeutics" and added, "Moreover, this significantly raised the standard of care for patients with non-resectable liver cancer."