Akeso Survival Data for Ivonescimab Misses Expectations, STAT Says

The biotech world is buzzing over Akeso’s PD-1/VEGF bispecific antibody, ivonescimab, following its April 2025 regulatory approval in China for first-line non-small cell lung cancer (NSCLC). While the drug’s progression-free survival (PFS) data were robust enough to secure approval, its interim overall survival (OS) results fell short of statistical significance, sparking a sharp sell-off in partner Summit Therapeutics’ shares and raising questions about its long-term promise.

The Trial’s Mixed Signals

The HARMONi-2 Phase III trial pitted ivonescimab against Merck’s Keytruda (pembrolizumab) in PD-L1-positive NSCLC patients. The results were a study in contrasts:
- PFS Triumph: Ivonescimab delivered a 49% reduction in disease progression (median PFS 11.14 months vs. 5.82 months for Keytruda), earning NMPA approval.
- OS Hurdle: An interim OS analysis showed a 22.3% risk reduction in death (HR 0.777) but failed to meet the trial’s stringent statistical threshold (α=0.0001) due to incomplete data (only 39% of expected deaths recorded).

The OS data’s lack of statistical significance, despite a hazard ratio below the clinically meaningful 0.8 threshold, left investors skeptical.

Market Reaction: A Case of “Almost There”

The news sent Summit Therapeutics (SMMT), Akeso’s U.S. partner, into a tailspin. Shares plummeted 37% to $23.21, while BioNTech (BNTX)—a strategic collaborator—fell 17% in sympathy.

Analysts cited two key concerns:
1. Statistical Rigor: The interim OS HR of .777, though clinically meaningful, fell short of the 30%+ risk reduction benchmark set by Keytruda’s prior approvals.
2. Competitive Benchmarking: While ivonescimab outperformed Keytruda in PFS, its OS edge was narrower than hoped, undermining its case as a “next-generation” standard of care.

Analysts Split on Clinical vs. Statistical Value

Citi’s Yigal Nochomovitz argued that the HR of 0.777 was “clinically meaningful” and could solidify in the HARMONi-7 global trial, which prioritizes OS as its primary endpoint. He noted that the interim’s strict alpha threshold (0.0001) skewed statistical interpretation, reserving power for later analyses.

However, others emphasized the high bar for oncology approvals. “The market wants to see statistical significance now, not later,” said one Wall Street analyst. “Investors are tired of ‘promising’ interim data that never pans out.”

The Bigger Picture: Why Ivonescimab Still Matters

Despite the OS stumble, ivonescimab’s dual PD-1/VEGF mechanism offers distinct advantages:
- Safety Profile: Comparable adverse events (including bleeding) to Keytruda, addressing concerns about anti-angiogenic therapies.
- Global Pipeline: Over 12 Phase III trials are ongoing across lung, breast, and other cancers, with the HARMONi-6 trial already showing PFS superiority over BeiGene’s Tevimbra in squamous NSCLC.

Akeso’s CEO, Dr. Xia Yu, framed the OS data as a “positive trend” and emphasized the drug’s 22% OS benefit over Keytruda—higher than Keytruda’s own 19% OS edge over chemotherapy in monotherapy settings.

The Bottom Line: A Wait-and-See Moment

The interim OS data’s failure to achieve statistical significance is a setback for ivonescimab’s near-term valuation. However, its PFS dominance and the HARMONi-7 trial’s potential to validate OS benefits suggest this is far from a death knell.

Key metrics to watch:
- Final OS Data: Expected once 232 and 280 deaths are recorded in HARMONi-2.
- Global Adoption: HARMONi-7’s design could address China-centric enrollment biases, bolstering the drug’s case for FDA/EU approval.

For now, investors are left in limbo. The $23.21 price tag for Summit reflects skepticism, but a positive HARMONi-7 readout could ignite a rally. Until then, the market will remain fixated on whether ivonescimab’s OS promise translates to hard numbers.

Conclusion: A Drug with Legs, but Still Running the Gauntlet

Akeso’s ivonescimab is a prime example of modern oncology’s “almost there” dilemma. Its PFS data and dual-mechanism profile position it as a transformative therapy, but the interim OS shortfall underscores the razor-thin margins between breakthrough and bust in drug development.

With China’s NSCLC market alone exceeding 1 million annual cases and global immuno-oncology sales projected to hit $100 billion by 2030, ivonescimab’s potential remains immense. The question now is whether its OS data matures into statistical significance—or if investors will demand more proof before betting big.

For investors, the lesson is clear: In a field where survival data reigns supreme, “clinically meaningful” trends aren’t enough. The final OS results will decide whether ivonescimab becomes a blockbuster or a cautionary tale.