Ivonescimab

BERLIN — At Europe’s largest cancer conference, Sunday’s main stage belonged to China. Medical conferences use their keynote sessions to highlight results from what the top researchers in the world think are the most important trials in their field. And at the European Society for Medical Oncology’s annual meeting, three of the four presentations during Sunday’s presidential symposium were for studies conducted in China, by Chinese companies. In the previous four years at ESMO, there wasn’t a single such high-level presentation from a China-only study. It’s yet another proof point for the rise of China biotech (not that the biopharma industry needed the reminder). One particularly striking China-run study at ESMO showed that, in certain lung cancer patients, an antibody-drug conjugate developed by Sichuan-based Kelun-Biotech cut the risk of death by 40% compared to chemotherapy, eliciting a round of applause from the thousands of audience members. The antibody drug-conjugate, known as sac-TMT, was approved in China for this indication earlier this month, but likely won’t get that same approval in the West for years. Kelun’s global partner Merck is running an analogous global Phase 3 trial that’s not expected to read out until 2028. That’s a long time for patients to wait for a therapy that seems likely to save lives. And at ESMO this weekend, it forced the question of whether Western regulators should reconsider their stances around China-only data. “With this level of evidence in the context of a Chinese trial, is a confirmation within a global study truly required for FDA and/or EMA approval?” Italian oncologist Antonio Passaro asked in his discussion of the trial results on stage after they were presented. And as more new and promising drugs emerge from China — sometimes at costs far below the US — will the FDA’s stance keep patients from benefiting? The FDA is highly unlikely to be open to the idea. In 2022, the agency notoriously rejected Eli Lilly’s application that used China-only data, which also effectively shut down a slew of US price disruption efforts using China-discovered drugs. On the other hand, the EMA has given approvals to two checkpoint drugs based on China data. But with Kelun’s drug, the question isn’t about a “me-too” medicine — like those EMA-approved checkpoint drugs. It’s about therapies that could meaningfully change the trajectory of patients’ disease. Another presentation on Sunday at ESMO was about ivonescimab, a PD-1xVEGF bispecific antibody from Chinese biotech Akeso, that’s seeking to rival those very checkpoint drugs. While it’s not approved in the US or Europe, CEO Michelle Xia told Endpoints News ahead of the symposium that ivonescimab has already been used to treat 40,000 patients in China since it was approved last year. The idea of changing how the US and Europe consider these types of drugs comes at a time when US-China geopolitics are particularly tense, making it even more unlikely. And the approach wouldn’t be without risk: One major safety, efficacy or data problem from a China-only trial could spoil future hopes. And in the US, others have argued for fully banning clinical trial data from studies conducted only in China. But for a very long time now, US patients have been able to access the newest, best drugs first — one argument companies here use for steep drug prices. What happens when the US drugmakers aren’t always first to the finish line anymore? — Lei Lei

Summit Therapeutics says it will submit an application to the FDA by the end of the year to review its PD-1xVEGF bispecific antibody, pressing forward with the program despite a mixed Phase 3 readout last month. But as it tries to forge ahead with regulators, Summit also appears to be readjusting to the reality that the drug, called ivonescimab, may not have the paradigm-shifting impact in oncology that some hoped. On its third-quarter earnings call Monday, Summit executives pointed out that the FDA has said it wants to see a statistically significant benefit in overall survival, a goal that ivonescimab didn’t achieve in a global Phase 3 trial. Now, the company is also looking at using the drug in combination with other therapies, a tactic already adopted by competitors. The decision to file with regulators is a part of Summit’s overall business strategy: It intends to submit a different application for each oncology indication, chief regulatory officer Urte Gayko said, rather than wait for a significant OS result in a different setting. “This particular package is ready now,” Gayko said on the call, which was dominated by questions about the filing. “We think this is the right opportunity, and we’re going forward.” The application plan is somewhat of a gamble, but there’s recent evidence the FDA might be amenable to it. Johnson & Johnson’s Rybrevant was approved in August 2024 with a significant result on progression-free survival but only a “positive trend” on overall survival. And AstraZeneca’s Datroway (Dato-DXd) in June won an accelerated approval based on a single-arm study using objective response rate as the primary endpoint. Rybrevant eventually reached statistical OS significance, according to a paper published last month in the New England Journal of Medicine . And Datroway’s benefit will be investigated in a separate, confirmatory study. AstraZeneca has not yet detailed such plans, but the FDA typically looks at overall survival in confirmatory trials. On the call, Gayko and other Summit leaders declined to get into specifics about their conversations with the FDA. Summit plans to seek approval in patients with EGFR-mutant locally advanced or metastatic non-squamous non-small cell lung cancer. It’s not a particularly large opportunity relative to other lung cancer areas where PD-(L)1 drugs like Merck’s Keytruda are dominant. Cantor Fitzgerald analyst Eric Schmidt previously told Endpoints News that the market size is roughly $500 million, a figure dwarfed by Keytruda’s nearly $30 billion in 2024 sales. The hope is that positive OS results could translate to success in other, larger markets. That comparison to Keytruda has popped up repeatedly as researchers, oncologists and investors have looked to the new PD-1xVEGF drugs as a potentially better version of the practice-changing megablockbuster. But reality has proven far more complicated. On Sunday, Summit’s partner Akeso presented China-only data that hit the primary progression-free survival endpoint in first-line advanced squamous non-small cell lung cancer. But questions still remain over how well it will translate to Western patients, and some analysts said the results signified the bispecifics will need to be used in combination regimens to maximize their benefit. Summit shares $SMMT were down about 3.3% on Monday. Without emphatic efficacy, the conversation has shifted to using the new drugs in combination with other treatments. Other companies testing PD-1xVEGF bispecifics — Bristol Myers Squibb and BioNTech’s pumitamig, and SSGJ-707 from Pfizer and 3SBio — are already considering broader combination use. On the call Monday, business chief Dave Gancarz said Summit was thinking about deploying the same tactic. “We’re working with multiple other companies in terms of collaborating in order to test ivonescimab in combination with multiple ADCs,” Gancarz said. “That will allow us, ultimately, to follow the data.” Gancarz’s comments, which came in response to an analyst question, reflect a growing possibility that Summit could get outflanked by rivals, since Summit does not have any ADCs in its pipeline and has yet to find a major pharma partner. Bloomberg reported on discussions this summer between Summit and AstraZeneca for a potential $15 billion partnership for ivonescimab, but nothing has been announced. Summit has signed a clinical trial collaboration with Revolution Medicines to test ivonescimab with RAS(ON) inhibitors, but that kind of agreement is different than the licensing deals for pumitamig and SSGJ-707. Summit also disclosed that it would once again be changing the trial design for HARMONi-3, a study in EGFR-positive non-small cell lung cancer patients. HARMONi-3 will now separate its enrolled patients into squamous and non-squamous groups, allowing for multiple statistical analyses. This may also result in two data readouts coming at different times, Summit said, with the primary PFS endpoint in squamous patients coming in the second half of 2026. Enrollment for non-squamous patients is expected to be completed around that time, with data in the second half of 2027. Originally, the trial was only designed to enroll only patients with squamous cancers. Then, it was changed to include non-squamous patients and report a dual overall survival endpoint. The trial change comes a few days after Summit said it would start testing ivonescimab in colorectal cancer, its first confirmed setting beyond lung cancer and an area where some experts believe the drug could have a more pronounced effect . Summit said on Monday that it will discuss this further in the first quarter of next year.