On April 25, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that its globally first-in-class PD-1/VEGF bispecific antibody, ivonescimab, has received approval from the National Medical Products Administration (NMPA) for its supplementary New Drug Application (sNDA) for use as a monotherapy for the first-line treatment of PD-L1-positive (TPS ≥ 1%) non-small cell lung cancer (NSCLC) in patients who are negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene mutations (Press release, Akeso Biopharma, APR 25, 2025, View Source [SID1234652158]). This indication marks Ivonescimab’s second major approval.
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The sNDA approval is based on the breakthrough results of the AK112-303/HARMONi-2 Phase III study, which is a randomized, double-blind, controlled study that directly compared ivonescimab with pembrolizumab in first line PD-L1 positive NSCLC.
Ivonescimab demonstrated a statistically significant improvement in the trial’s primary end point, median progression-free survival (PFS) when compared to pembrolizumab, with a median PFS of 11.14 months, achieving a hazard ratio (HR) of 0.51 reducing the risk of disease progression or death by 49%.
An interim analysis of OS conducted at 39% data maturity (α=0.0001), indicated a clinically meaningful improvement in OS with ivonescimab compared to pembrolizumab, with a hazard ratio (HR) of 0.777, reflecting a 22.3% reduction in the risk of death.
Ivonescimab is the first therapy to achieve statistically significant positive results in a Phase III trial compared with pembrolizumab in a head-to-head setting.
Ivonescimab represents a new, more effective, and safer "chemotherapy-free" option for the first-line treatment of NSCLC.
Ivonescimab is the first bispecific antibody approved globally with a dual "cancer immunotherapy + anti-angiogenesis" mechanism. It has already shown significant positive results in three Phase III trials for lung cancer, including 1) treatment for EGFR-TKI-resistant NSCLC, 2) comparison with pembrolizumab in PD-L1-positive NSCLC, and 3) treatment in combination with chemotherapy versus tislelizumab in combination with chemotherapy in squamous NSCLC.
Professor Zhou Caicun, principal investigator of the HARMONi-2 trial, director of the Department of Oncology at the Shanghai East Hospital, Tongji University, commented:
"The Phase III HARMONi-2 study demonstrated that ivonescimab offers significant improvements in progression-free survival (PFS) and overall survival (OS) compared to pembrolizumab. This breakthrough provides a safer and more effective first-line treatment option for NSCLC, particularly beneficial for patients who need better efficacy or quality of life, or those who are not suitable for chemotherapy due to its side effects.
Ivonescimab has also gained widespread recognition in treating EGFR-TKI-resistant NSCLC. The recent Phase III trial combining ivonescimab with chemotherapy, compared to tislelizumab for squamous NSCLC, showed promising positive results. Ivonescimab is now positioned as a new standard of care for both first- and second-line treatment in lung cancer. We are optimistic about its continued success in global Phase III trials and its potential to redefine cancer treatment standards worldwide."
Dr. Xia Yu, Founder, Chairwoman, President, and CEO of Akeso, commented:
"We are thrilled to announce the approval of ivonescimab as a first-line treatment for PD-L1-positive NSCLC, a major breakthrough in cancer immunotherapy. This milestone is a result of the dedication of investigators, participants, and patients, and we sincerely thank all of them. We also appreciate the regulatory authorities for their efficient and diligent review, which enables us to offer this new treatment to patients in China.
Ivonescimab has shown superior efficacy over pembrolizumab in the HARMONi-2 Phase III trial, becoming the first therapy to achieve this globally. Positive results so far from three pivotal Phase III lung cancer trials further establish ivonescimab as a next-gen IO treatment with strong global potential.
The clinical data highlights ivonescimab’s exceptional efficacy and safety benefits for patients across various cancer types. Beyond lung, ivonescimab has demonstrated promising potential as first-line treatment for other key cancers, including breast, head and neck, biliary tract, and colorectal cancer, supported by, over 12 ongoing Phase III trials. Akeso, along with our partner Summit, are committed to advancing ivonescimab as a cornerstone of global cancer immunotherapy, aiming to provide safer, more effective treatment options for patients worldwide."