FDA Accepts Elevar's Resubmitted Rivoceranib and Camrelizumab Application for First-line Hepatocellular Carcinoma Treatment

Elevar Therapeutics, Inc., a subsidiary of HLB Co., Ltd., has announced that the U.S. Food and Drug Administration (FDA) has accepted the resubmission of a New Drug Application (NDA) for their investigational drug rivoceranib. This drug is an oral VEGF-TKI and, when combined with camrelizumab, a PD-1 inhibitor, is aimed at treating unresectable or metastatic hepatocellular carcinoma (uHCC) as a first-line systemic treatment. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date for March 20, 2025.

Chris Galloway, M.D., senior vice president of clinical and medical affairs at Elevar Therapeutics, expressed confidence in the combination of rivoceranib and camrelizumab, citing significant improvements in overall survival demonstrated in the pivotal CARES-310 trial. According to Galloway, the combination has shown a manageable safety profile compared to currently approved uHCC therapies, and Elevar is committed to bringing this treatment to market.

The resubmission is backed by the final analysis of the Phase 3 CARES-310 study, which was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The study reported a median overall survival (mOS) of 23.8 months, the longest for any treatment in a global Phase 3 trial for patients with uHCC. This indicates that the combination of camrelizumab and rivoceranib continues to show sustained long-term survival benefits for these patients.

The efficacy results were consistent across all subgroups, suggesting that the combination therapy could benefit a global uHCC population. The data also showed consistent efficacy among patients with both viral and non-viral etiologies.

The CARES-310 study was an international, randomized, open-label, Phase 3 trial involving 543 patients with uHCC who had not previously received systemic treatment. It was the first study to demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits with immunotherapy combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKIs as the first-line treatment for uHCC. In the primary analysis of PFS, conducted in May 2021, and the interim analysis of OS, conducted in February 2022, significant improvements were observed with the combination of camrelizumab (C) and rivoceranib (R) compared to sorafenib (S).

In the final analysis of the CARES-310 study, after approximately 16 months of additional follow-up, median OS was significantly prolonged with C+R compared to S (23.8 months vs. 15.2 months). The OS rate for C+R was 49.0% at 24 months and 37.7% at 36 months, compared to 32.6% and 24.8% for S, respectively. The OS benefits with C+R were generally consistent across various subgroups, including geographical regions, races, and etiologies. The benefits in PFS, objective response rate (ORR), and duration of response (DoR) with C+R compared to S persisted after prolonged follow-up. Safety data aligned with the interim OS analysis, with no new safety signals noted. The extended follow-up confirmed the favorable benefit-to-risk profile of C+R, supporting it as a new first-line treatment option for uHCC.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, often developing in individuals with chronic liver inflammation due to viral and non-viral causes. HCC generally has a poor prognosis with limited treatment options, representing an ongoing urgent medical need.

Rivoceranib is a small-molecule tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptors (VEGFRs), a primary pathway for tumor angiogenesis. It is being studied as a monotherapy and in combination with other treatments in various solid tumor indications. It has shown a comparable safety profile to other TKIs and VEGF inhibitors in clinical trials and has been granted orphan drug designations for gastric cancer, adenoid cystic carcinoma, and uHCC.

Camrelizumab is a humanized monoclonal antibody that targets the programmed death-1 (PD-1) receptor. It has shown success in treating a variety of cancers and is currently approved for multiple indications in China. The U.S. FDA has granted orphan drug designation to camrelizumab for advanced HCC.

Elevar Therapeutics holds the global rights (excluding China) to rivoceranib and has partnered with HLB-LS in South Korea for its development and marketing.