Ivonescimab Improves Survival in Head-to-Head Trial Against Keytruda, but Market Reaction Is Cautious

Ivonescimab, an immuno-oncology drug co-developed by Chinese biotech company Akeso and U.S.-based Summit Therapeutics, demonstrated improved overall survival (OS) in a head-to-head trial against Keytruda.

According to Fierce Pharma on the 3rd (local time), Akeso and Summit announced that ivonescimab showed a statistically significant and clinically meaningful OS improvement over Merck (MSD)’s Keytruda in the HARMONi-2 trial in Chinese patients with PD-L1-positive non-small cell lung cancer receiving first-line treatment.

However, unlike the market reaction when ivonescimab’s progression-free survival (PFS) advantage was first reported in May 2024, the response was subdued. Akeso shares rose just 3.4% on the Hong Kong stock exchange on the 4th, the day after the announcement.

HARMONi-2 is the fourth phase 3 trial in which ivonescimab has met the OS endpoint. However, debate continues over whether it can succeed on the global stage, given that its efficacy has so far been demonstrated only in China.

Evercore ISI analysts noted, “At some point, the market has to ask whether it is appropriately reflecting the likelihood of success for ivonescimab’s global development program.” Citi analysts said the results “support the broader narrative that ivonescimab outperforms PD-1 drugs in multiple settings.”

Ivonescimab’s bid to replace Keytruda has not been smooth. In an unplanned interim analysis requested by Chinese regulators last year, ivonescimab was found to reduce the risk of death by 22.3% compared with Keytruda, but concerns about the magnitude of the early effect sent Summit shares sharply lower.

At the time, Michelle Xia, CEO of Akeso, explained that HARMONi-2 was designed with OS as a secondary endpoint only.

Following this announcement, analysts began analyzing the numbers based on limited information. Citi estimated that the latest results likely showed an OS improvement of more than 30%, while Evercore said the magnitude could be close to or greater than 30%.

Detailed data are expected to be presented at the World Conference on Lung Cancer (WCLC), which will be held in Seoul from the 12th to the 15th. However, because the first-line standard of care is Keytruda plus chemotherapy, rather than Keytruda alone, except in the high PD-L1 expression subgroup, the practical significance in clinical practice may be limited.

Summit is conducting the global HARMONi-3 trial, which compares ivonescimab plus chemotherapy with Keytruda plus chemotherapy, with final PFS results expected this year.

Ivonescimab was first approved in China in 2024 for certain patients with non-small cell lung cancer. Last week, it also reported its first phase 3 success outside lung cancer, surpassing AstraZeneca’s Imfinzi combination therapy in first-line treatment of biliary tract cancer.