Tuesday, July 18, 2023
Elevar Therapeutics, a biopharmaceutical company committed to enhancing treatment options for patients with limited therapeutic alternatives, has announced that the U.S. Food and Drug
Administration (FDA) has accepted its new drug application (NDA) for rivoceranib, an investigational oral TKI, in combination with camrelizumab, a PD-1 inhibitor. The NDA aims to seek approval for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of May 16, 2024.
The NDA submission is supported by data from the Phase 3 CARES 310 study (NCT03764293), which demonstrated significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared to the standard first-line treatment, sorafenib. The study enrolled 543 patients across 13 countries/regions and showed a median OS of 22.1 months and a median PFS of 5.6 months for the rivoceranib and camrelizumab combination.
Elevar Therapeutics is focused on advancing the treatment options for patients with unresectable hepatocellular carcinoma and is looking to expedite the availability of the combination therapy following potential approval. The company is also exploring the use of rivoceranib as a monotherapy for adenoid cystic carcinoma (ACC) and investigating its potential in combination therapies for various tumor cell types.
Apart from the FDA acceptance, the combination therapy of rivoceranib and camrelizumab has already received approval from the National Medical Products Administration (NMPA) in China as a first-line treatment for liver cancer in February 2023.
Hepatocellular Carcinoma (HCC) is the most common form of primary liver cancer and is frequently associated with chronic liver diseases like hepatitis B or hepatitis C. Patients with HCC face a poor prognosis and limited treatment options, highlighting the urgent need for effective therapies.
Rivoceranib is a small-molecule tyrosine kinase inhibitor (TKI) that selectively targets vascular endothelial growth factor receptor 2 (VEGFR-2), a crucial pathway involved in tumor angiogenesis. By inhibiting VEGFR-2, rivoceranib demonstrates its potential to impede tumor growth and disease progression, offering a promising approach to cancer treatment.
Ongoing clinical studies are investigating rivoceranib as both a monotherapy and in combination with chemotherapy and immunotherapy for various solid tumor indications. These include unresectable hepatocellular carcinoma (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy), and colorectal cancer (in combination with Lonsurf®). Rivoceranib received its first approval as a TKI for gastric cancer in China in November 2014 and was subsequently approved as a first-line treatment for unresectable hepatocellular carcinoma in February 2023. The drug has been extensively studied in over 6,000 patients worldwide, demonstrating a safety profile comparable to other TKIs and VEGF inhibitors. Orphan drug designations have been granted for gastric cancer (U.S., EU, and South Korea), adenoid cystic carcinoma (U.S.), and unresectable hepatocellular carcinoma (U.S.).
Camrelizumab (SHR-1210) is a humanized monoclonal antibody that targets the programmed death-1 (PD-1) receptor. By blocking the PD-1/PD-L1 signaling pathway, camrelizumab has shown promising results in a wide range of solid and hematological cancers. Developed by Hengrui Pharmaceuticals, camrelizumab has been studied in more than 5,000 patients and is currently being investigated in 50 clinical trials for various tumor types, including liver cancer, lung cancer, gastric cancer, and breast cancer.
In China, camrelizumab is marketed under the brand name AiRuiKa® and has received approval for multiple indications, both as a monotherapy and in combination with chemotherapy. These indications include second-line treatment for hepatocellular carcinoma, relapsed/refractory classic Hodgkin's lymphoma (third-line), esophageal squamous cell carcinoma (second-line), and nasopharyngeal carcinoma (third-line or further). The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to camrelizumab for advanced hepatocellular carcinoma in April 2021.