Akeso's antibody beats Keytruda in China lung cancer trial, shares soar

Summit Therapeutics and Akeso’s experimental bispecific antibody, ivonescimab, has recently made significant strides in the treatment of non-small cell lung cancer (NSCLC). Notably, the drug demonstrated a substantial improvement in progression-free survival (PFS) over Keytruda, a well-established PD-1 inhibitor, during the phase 3 HARMONi-2 trial. This trial, conducted in China, compared ivonescimab to Keytruda in patients with locally advanced or metastatic NSCLC expressing the PD-L1 protein.

Ivonescimab employs a unique dual-targeting mechanism by binding to both the PD-1 protein and the vascular endothelial growth factor (VEGF) protein. This approach is thought to be beneficial due to the higher expression of both PD-1 and VEGF in tumor tissues and the tumor microenvironment compared to normal tissues. This dual action could potentially offer a significant advantage in treating solid tumors.

The HARMONi-2 trial's results showed a statistically significant and clinically meaningful improvement in PFS with ivonescimab compared to Keytruda monotherapy, fulfilling the primary endpoint of the study. The benefit in PFS was observed across various patient subgroups, including those with both low and high PD-L1 expression and those with different histological types of NSCLC, such as squamous and non-squamous.

Despite these promising results, Summit and Akeso face several challenges before ivonescimab can compete with Keytruda and other PD-1 inhibitors in the U.S. market. To gain approval as a monotherapy for NSCLC, ivonescimab will likely need to demonstrate an overall survival (OS) benefit, in addition to its PFS results. Moreover, the trial's China-only design may pose difficulties in obtaining approval from the U.S. Food and Drug Administration (FDA), considering the agency's historical precedents.

Summit and Akeso have not yet released detailed trial results, but they plan to present their findings at a major medical conference later this year. Analysts have responded positively to the head-to-head trial results, with Evercore ISI analyst Cory Kasimov describing the findings as "very encouraging." This trial is reportedly the first instance where a phase 3 candidate has shown a statistically significant PFS improvement over Keytruda in NSCLC. Citigroup’s Yigal Nochomovitz also noted the potential of ivonescimab across multiple solid tumors, adding to the positive outlook for the drug.

Summit holds the rights to ivonescimab in the U.S., Canada, Europe, and Japan, while Akeso manages the drug in China and Australia. Following the announcement of the trial results, Summit's stock surged by roughly 270%, although it experienced a decline of about 21% the following morning.

These encouraging results come shortly after ivonescimab received approval in China, in combination with chemotherapy, for treating EGFR-mutated locally advanced or metastatic non-squamous NSCLC in patients who progressed after tyrosine kinase inhibitor (TKI) therapy.

In addition to the monotherapy trial against Keytruda, Akeso and Summit are exploring ivonescimab in several other competitive settings. These include a combination with chemotherapy against BeiGene’s Tevimbra in locally advanced or metastatic squamous NSCLC, and another head-to-head trial against Keytruda as a potential first-line treatment for squamous NSCLC patients.

The initial success of ivonescimab has generated optimism about its potential to become a significant player in the treatment of NSCLC and possibly other solid tumors, pending further validation and regulatory approvals.

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