Akeso's Ivonescimab Shows Promise in Head-to-Head Trial Against Keytruda, But Investors Remain Cautious

Akeso, a Chinese biopharmaceutical company, has released the first overall survival data from its high-profile head-to-head trial comparing its PD-1xVEGF bispecific antibody, ivonescimab, with Merck's Keytruda in first-line PD-L1-positive non-small cell lung cancer (NSCLC). The results have sparked mixed reactions from investors and analysts, highlighting the complexities of interpreting clinical trial data in the competitive oncology landscape.

Overall Survival Data and Market Response

In a recent announcement regarding ivonescimab's Chinese approval, Akeso revealed that the drug reduced the risk of death by 22.3% compared to Keytruda at an interim analysis of the HARMONi-2 trial. This data point, while potentially clinically significant, did not meet the stringent statistical significance threshold set for the interim analysis, which had an alpha assignment of 0.0001.

The market's reaction to this news was swift and severe, with Summit Therapeutics—Akeso's partner for ivonescimab—experiencing a nearly 37% drop in stock price on the Nasdaq before trading was halted. This dramatic decline suggests that investors had higher expectations for the overall survival benefit or were hoping for clearer statistical significance at this stage of the trial.

Clinical Efficacy and Regulatory Milestone

Despite the lukewarm reception of the overall survival data, ivonescimab has demonstrated impressive efficacy in other metrics. The Chinese approval was based on progression-free survival data, which showed that ivonescimab reduced the risk of progression or death by 49% compared to Keytruda. Patients treated with ivonescimab lived a median of 11.14 months without disease progression, nearly doubling the 5.82 months observed in the Keytruda arm.

This approval marks a significant milestone for Akeso and potentially signals a shift in the treatment paradigm for NSCLC in China. The drug's performance in progression-free survival is particularly noteworthy, as it surpasses the benefits typically seen with established therapies in this setting.

Expert Analysis and Future Outlook

While the market reaction was negative, some analysts view the overall survival data more positively. Citi analyst Yigal Nochomovitz, Ph.D., described the initial overall survival number as an "excellent result," noting that the statistical bar of 0.0001 was "exceedingly high." Nochomovitz emphasized that the 0.777 hazard ratio is "solidly below" the 0.8 threshold often cited by oncologists as clinically meaningful.

The future of ivonescimab may hinge on the global HARMONi-7 trial being conducted by Summit Therapeutics. This phase 3 study, which is comparing ivonescimab to Keytruda in first-line, PD-L1-high NSCLC patients, is well-powered to detect overall survival benefits. Nochomovitz suggests that if similar results to the Chinese trial are observed, U.S. physicians would likely be eager to adopt a treatment that offers a 22-23% relative risk reduction in death compared to the current standard of care.

As the pharmaceutical industry closely watches the development of novel bispecific antibodies and their potential to challenge established immunotherapies, the full results of the HARMONi-2 and HARMONi-7 trials will be crucial in determining ivonescimab's place in the evolving landscape of cancer treatment.