With ivonescimab’s data coming solely from China, its prospects in the U.S., where Summit owns the rights, remain up in the air.
Summit Therapeutics’ and Akeso’s closely watched PD-1/VEGF immunotherapy ivonescimab was given clearance by China’s National Medical Products Administration on Friday for the first-line treatment of certain patients with non-small cell lung cancer.
The Chinese approval could be a sign of ivonescimab’s regulatory prospects in the U.S., though analysts seem to be split on the matter, particularly given interim findings Friday from the HARMONi-2 trial, in which the PD-1/VEGF therapy failed to significantly boost overall survival (OS) in patients with PD-L1-positive non-small cell lung cancer (NSCLC) compared to Keytruda. Data maturity for this readout was 39%.
“King Keytruda still reigns,” BMO Capital Markets analysts wrote in reaction to the data drop. The issue of ivonescimab’s failure to improve OS “adds questions to ivonescimab’s ability to challenge [Keytruda] in NSCLC,” they added, calling OS the “gold standard in oncology.” These findings, according to BMO, could “incrementally benefit” Merck, which has been facing share pressure from the emerging class of PD-1/VEGF inhibitors.
On the other hand, Truist Securities skewed more in favor of Summit and Akeso, writing on Friday that they expect final OS in HARMONi-2 to be statistically significant. Truist argued that ivonescimab’s Chinese label and HARMONi-2 readout provide a “much earlier look” at its Phase III performance, “and so it is unsurprising” that the OS outcome fell short of significance.
Still, Truist is “encouraged that even at this early look, the OS curves are separating.” The analysts contend that ivonescimab could demonstrate significantly better OS by the study’s final analysis, “if not potentially earlier.” A more mature readout is expected by year-end, according to Truist.
The approval is a win for Akeso, which developed the drug and controls ivonescimab’s rights in China but the lingering questions regarding the molecule’s OS numbers remain a challenge for Summit, which secured the rights for the molecule in the U.S., Canada, Europe and Japan in 2022 for $500 million and up to $5 billion in downstream payments.
Following the news of the approval in China, Summit’s stock immediately shed about one-third of its value, where it continues to sit Monday morning.
Ivonescimab is a bispecific antibody that targets both the PD-1 and VEGF pathways, an emerging approach to cancer that captured the industry’s attention in September 2024 after Summit and Akeso declared triumph over Keytruda, touting PFS in HARMONi-2. The partners continue to build their case for ivonescimab, with another Phase III readout last week claiming its PFS superiority over BeiGene’s Tevimbra in NSCLC.
Many analysts remain skeptical, however, noting the need for more data and flagging the fact that ivonescimab has thus far only been trialed in China, which presents a formidable barrier to U.S. approval.
In an interview with BioSpace last September, Christiana Bardon, co-managing partner at MPM BioImpact, said ivonescimab still needs to prove itself in terms of OS, an important metric that many doctors consider when making prescribing decisions.
Bardon and other experts also emphasized the need for more diverse data, noting that using Chinese-only populations could potentially skew the findings due to factors such as genetics and cultural differences in reporting side effects. Safety, in particular, stood out to Bardon as a possible point of contention for the FDA, given that there were very few grade 3 side effects in HARMONi-2.
“[Adverse events] are probably underestimated compared to what we would see in a Western-based population,” she said.
To address these concerns, Summit is running the Phase III HARMONi-3 trial, a global study that could pave the way for a U.S. approval application. That study is currently enrolling patients.
