Akeso's sBLA for Ivonescimab in First-Line Therapy for PD-L1 Positive NSCLC Accepted by NMPA
Tuesday, July 30, 2024
Akeso (9926.HK) is pleased to announce that the China National Medical Products Administration (NMPA) has accepted the supplemental biologics license application (sBLA) for ivonescimab injection (依达方®), the world's first PD-1/VEGF bispecific antibody drug. This application is for the use of ivonescimab as a monotherapy in the first-line treatment of PD-L1 positive (PD-L1 TPS≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC).
Ivonescimab represents the first bispecific antibody drug approved for a combined approach of "tumor immunotherapy + anti-angiogenesis." Its new indication as a first-line monotherapy for PD-L1 positive NSCLC follows its initial approval for treating EGFR-mutant non-squamous NSCLC that has progressed after EGFR-TKI therapy. Ivonescimab is set to become a key treatment option for both first-line and second-line lung cancer therapies.
This application is supported by data from the HARMONi-2 (AK112-303) study. An interim analysis by the Independent Data Monitoring Committee (IDMC) showed highly positive results. In the intent-to-treat (ITT) population, ivonescimab monotherapy significantly improved progression-free survival (PFS) compared to pembrolizumab monotherapy, with a hazard ratio (HR) that exceeded expectations.
Professor Zhou Caicun, the principal investigator of the HARMONi-2 study and director of the Oncology Department at East Hospital affiliated to Tongji University, expressed enthusiasm about ivonescimab's potential: “We eagerly anticipate ivonescimab becoming the new standard treatment for first-line lung cancer, providing a superior ‘chemotherapy-free’ option for patients. The success of the HARMONi-2 study underscores the immense value of ivonescimab’s synergistic dual anti-tumor mechanism of ‘tumor immunotherapy + anti-angiogenesis.’”
Akeso, remarked: “Achieving this milestone for first-line lung cancer therapy so soon after ivonescimab's second-line approval is significant. We extend our deepest gratitude to all Akeso colleagues, experts, and participants involved in this project. The approval fills a critical clinical gap in global lung cancer immunotherapy, aligning with our commitment to providing effective solutions for patients.”
Dr. Xia highlighted the importance of the HARMONi-2 study, noting ivonescimab’s efficacy and safety. She emphasized its potential as a cornerstone in tumor immunotherapy, particularly when used in combination with ADC drugs or other novel anti-cancer drugs. “We are excited to share ivonescimab’s robust clinical research data with global regulatory agencies, aiming for worldwide approval to benefit patients everywhere.”
Ivonescimab, known as SMT112 in Summit’s licensed territories (the United States, Canada, Europe, and Japan) and as AK112 in China and Australia, is an innovative bispecific antibody. It combines the effects of PD-1 immunotherapy with VEGF-mediated anti-angiogenesis in one molecule. Ivonescimab demonstrates unique cooperative binding to its targets, showing higher affinity when both PD-1 and VEGF are present.
This dual targeting strategy is potentially advantageous as both PD-1 and VEGF are often expressed at higher levels in tumor tissues and the tumor microenvironment (TME) compared to normal tissues. Ivonescimab’s tetravalent structure (with four binding sites) enables stronger interactions in the TME, with an 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and a four-fold increased affinity to VEGF in the presence of PD-1 in vitro. This design, combined with a half-life of 6 to 7 days, aims to improve efficacy while minimizing side effects and ensuring safety.
Ivonescimab was discovered by Akeso Inc. and is undergoing multiple Phase III clinical trials. Over 1,600 patients worldwide have participated in ivonescimab studies. Summit Therapeutics has initiated clinical development of ivonescimab in NSCLC, with patient enrollment beginning in 2023 for two Phase III trials, HARMONi and HARMONi-3.
Source: prnewswire.com
