Akeso·Seamless Ibezamib, 3 Phase Shows Survival Superiority Over Keytruda
Survival Advantage Over Keytruda
Akeso's Ibezamib is a bispecific antibody that simultaneously blocks PD-1 and VEGF-A. The HARMONi-2 Phase 3 trial, conducted at 55 institutions in China, enrolled 398 patients with PD-L1 TPS ≥1%, EGFR·ALK mutation-negative, advanced non-small cell lung cancer (NSCLC), randomly assigned to Ibezamib (198 patients) and Keytruda (200 patients). A pre-specified interim analysis showed statistically significant and clinically meaningful improvement in overall survival (OS) over Keytruda, achieving the key secondary endpoint. The hazard ratio and median will be disclosed at a future conference, so the focus of this announcement is not the direction but the statistical confirmation of survival superiority.
Already Proven Tumor Inhibition
The primary endpoint of progression-free survival (PFS) in HARMONi-2 was 11.14 months for Ibezamib and 5.82 months for Keytruda, with a hazard ratio of 0.51 and a p-value less than 0.0001. The objective response rate (ORR) was also higher for Ibezamib at 50.0% versus 38.5% for Keytruda. This OS achievement strengthens clinical credibility by showing that early imaging advantages translated into actual survival extension. The design logic of combining PD-1 inhibition to suppress immune evasion and VEGF-A neutralization to block tumor angiogenesis in a single molecule is also reinforced.
From China Approval to Global Validation
The China NMPA approved Ibezamib in combination with pemetrexed and carboplatin for EGFR-TKI-treated, EGFR-mutated, non-squamous NSCLC on May 24, 2024. On April 25, 2025, it approved Ibezamib as a first-line monotherapy for PD-L1-positive advanced NSCLC based on HARMONi-2, and it is now commercially available. In the U.S., a separate global HARMONi-3 trial is being used as the basis for a biological license application (BLA) for Ibezamib in combination with chemotherapy for EGFR-mutated patients, with an FDA target action date of November 14, 2026. Because HARMONi-2 is a single-region Chinese study, Seamless's global development program and Western patient data will be key evidence for U.S. and European value assessments.
Changing Competitive Landscape in the Megaphone PD-1 Market
The current standard of care, Merck's Keytruda (pembrolizumab), is a PD-1 monoclonal antibody. The combined 2025 sales of Keytruda and its subcutaneous formulation QLEX were USD 31.68 billion. Ibezamib's survival advantage in direct comparison gives Akeso and Seamless a clinical differentiation to target this large immunotherapy revenue base. A direct competitive pipeline is BioNTech and Bristol-Myers Squibb's PD-L1·VEGF-A bispecific antibody Pemigatin (BNT327·BMS-986545), which is in global Phase 2/3 ROSETTA Lung-02 for first-line NSCLC. Therefore, the competitive axis is shifting from comparisons between simple PD-1 inhibitors to next-generation combined mechanisms controlling immune checkpoints and angiogenesis.
Ibezamib secured a PFS hazard ratio of 0.51 and statistically significant OS superiority over Keytruda in a 398-patient Phase 3 trial, creating a basis to re-evaluate the China-approved product as a global late-stage asset. Given that Keytruda and QLEX had 2025 sales of USD 31.68 billion, changes in first-line NSCLC market share will directly impact the value of both Merck and Seamless. In the short term, the upcoming OS hazard ratio and median, and the FDA's November 14, 2026 BLA decision for a separate indication, are key catalysts. In the medium to long term, comparisons with Pemigatin's global Phase 2/3 trial will determine efficacy, VEGF-related safety such as bleeding and hypertension, and reproducibility in Western patients. For R&D professionals, this signals a shift in hiring and investment demand from PD-1 monotherapy to late-stage clinical strategies that simultaneously regulate the tumor microenvironment and angiogenesis.