New Summit data could slow US approval plans for PD-1/VEGF drug

Dive Brief:

• A dual-acting drug developed by Summit Therapeutics and Akeso delayed tumor progression in a Phase 3 lung cancer trial but didn’t extend survival, complicating its potential path to approval in the U.S.
• When administered alongside chemotherapy, the drug, known as ivonescimab, reduced the risk of death or disease progression by 48% compared to chemotherapy alone in patients whose non-small cell lung cancer has a mutation in a gene called EGFR. However, a 21% reduction in death risk, specifically, didn’t meet the threshold for statistical significance, Summit said in a statement Friday.
• Summit intends to seek Food and Drug Administration approval based on the study results. Yet in its statement, the company indicated the timing of a filing is uncertain given the agency has made clear that a survival benefit is “necessary” to support a submission. Summit shares fell by nearly 20% early Friday.

Dive Insight:

Ivonescimab is the frontrunner among more than a dozen medicines that simultaneously block the proteins PD-1 and VEGF and are seen as a way to build upon widely used cancer immunotherapies like Keytruda. Its success or failure has broad implications for cancer research, making each study readout a closely scrutinized event among scientists and investors.

So far, the results Summit and its China-based partner Akeso have accrued are painting a mixed and incomplete picture. A Phase 3 trial in China in non-small cell lung cancer found the drug cut the risk of disease progression or death in half compared to Keytruda, a striking, first-of-its-kind result that sparked interest and investment in PD-1/VEGF drugs. But ivonescimab hasn’t yet clearly extended survival in that same study.

Summit’s drug also hasn’t yet proven superior to the Keytruda-chemotherapy regimen that’s standard therapy in many lung cancers. The results accrued so far were from trials in China, too, not the kind of multi-country test the FDA prefers.

The data revealed Friday were meant to address one of those issues, proving that the benefits Summit and Akeso have observed in China would be replicated in a broader study population. Summit, for its part, said invonescimab’s effects on tumor progression were “clinically meaningful” in “both Asia and ex-Asia sub-populations,” and demonstrated the “consistency” of the drug’s benefit in each group. The outcome also closely resembled what Akeso reported in a similar study of EGFR-mutated lung cancer in China. No new safety issues were observed either.

The data “demonstrates the potential benefit ivonescimab has to bring to patients around the world, including the United States,” said Summit chairman and co-CEO Robert Duggan, in a statement.

Still, the lack of a clear impact on survival in the trial, at least so far, could slow ivonescimab’s path to approval in the U.S. Summit implied its results could improve, as the follow-up time for “western” patients in its trial was less than the median overall survival figure when data were analyzed. It also noted how no FDA-approved regimens in the setting in which ivonescimab was tested have demonstrated a statistically significant effect on survival.

The FDA’s insistence on such data, though, “will weigh into Summit’s considerations” as to when it might make a submission, the company said.

The agency’s “high bar for demonstrated overall survival benefit make approval less likely,” wrote Leerink Partners analyst Daina Graybosch, in a Friday note to investors. Just this week, Merck and Daiichi Sankyo withdrew an approval application in EGFR lung cancer after a drug they’ve been developing failed to improve survival in a clinical trial.

Summit will disclose specific findings at a future medical meeting.

A study evaluating ivonescimab and chemotherapy against Keytruda and chemotherapy in non-small cell lung cancer is ongoing. A readout is expected in 2027, according to a federal database.

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