Recently, Hengrui Pharmaceutical (600276) announced that the company has received a complete reply (Complete Response Letter) from the US Food and Drug Administration (FDA) regarding the application for biological product licensing (BLA) of carrazumab combined with apatinib for first-line treatment of unresectable or metastatic hepatocellular carcinoma patients. In the reply letter, FDA said that it would conduct a comprehensive assessment based on the enterprise's complete response to the defects in the production site inspection.CrashboombangAnd due to travel restrictions in some countries, FDA said that the necessary biological research monitoring program (BIMO) clinical tests for the project could not be completed during the review cycle.
According to understanding from the industry, the full reply letter, which is commonly known as CRL,FDA in the industry, will explain in detail the possible defects and risks in the CRL, and put forward proposals. If the applicant can complete the changes within the specified time, CRL will not actually affect the final approval. In other words, the US listing of Hengrikarelli's bead monoclonal antibody has been delayed. The previous triplet monoclonal antibody FDA, which also received CRL, was finally approved in October last year.
Hengrui Pharmaceutical said that the company plans to actively maintain close communication with FDA and resubmit its listing application as soon as possible, so that the product can be approved in the United States as soon as possible.
It is understood that the listing application is based on the positive results of an international multicenter phase III clinical study (CARES-310 study). The study, led by Professor Qin Shukui of Nanjing Tianyinshan Hospital affiliated to China Pharmaceutical University, with the participation of 95 centers in 13 countries around the world, showed significant survival benefits and tolerable safety in the first-line treatment of advanced unresectable or metastatic liver cancer. The median overall survival time (mOS) was 22.1months, and the risk of death was significantly reduced by 38%. In early 2023, Carrilizumab combined with apatinib was approved by the State Drug Administration (NMPA) for first-line treatment in patients with unresectable or metastatic hepatocellular carcinoma. Among all the approved indications for first-line treatment of hepatocellular carcinoma, carrazumab combined with apatinib regimen has become the treatment regimen 2-7 with the longest median OS study. In July 2023, the research data were published in the main issue of the Lancet (The Lancet,IF)Crashboombang: 168.9).
About liver cancer
According to the data released by GLOBOCAN 2022, there are about 866100 new cases of liver cancer in the world in 2022, accounting for the sixth of all malignant tumors, and about 758700 new deaths of liver cancer, accounting for the third of all malignant tumors.
About Carrilizumab.
Carrilizumab (trade name: Erika ®) is a humanized PD-1 monoclonal antibody independently developed by Hengrui Medicine, which was approved by the State Drug Administration (NMPA) in May 2019. Carrilizumab has high affinity for PD-1 and can significantly prolong the overall survival time of patients in a variety of solid tumor treatment studies. At present, 9 indications have been approved in China, including lung cancer, liver cancer, esophageal cancer, nasopharyngeal carcinoma and lymphoma. It is a domestic PD-1 product with the leading number of approved indications and covering tumor species.
About Apatinib.
Apatinib (trade name: Aitan ®) is a small molecular tyrosine kinase inhibitor for vascular endothelial growth factor receptor (VEGFR) developed by Hengrui Pharmaceutical. It was approved by the State Drug Administration (NMPA) in October 2014. At present, three indications have been approved in China. they are monotherapy for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma that has progressed or relapsed after at least two kinds of systematic chemotherapy, advanced hepatocellular carcinoma that has failed or intolerable after at least first-line systematic treatment, and combined with carraizumab for unresectable or metastatic hepatocellular carcinoma.
References:
1.Qin S, Chan SL, Gu S, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310)Crashboombang: a randomised, open-label, international phase 3 study. Lancet. 2023 Sep 30th 402 (10408)Crashboombang: 1133-1146.
2.Yau T, Park JW, Finn RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised,multicentre, open-label, phase 3 trial. Lancet Oncol 2022; 23: 77
