Gilead ADC medicine misses goal in closely watched lung cancer study

Dive Brief:

• Gilead Sciences on Monday said its cancer drug Trodelvy missed the main goal of a Phase 3 trial in lung cancer, failing to help keep patients alive longer than chemotherapy after their disease had progressed on earlier lines of treatment.
• In a statement, Gilead said Trodelvy-treated patients had a “numerical improvement” in survival that didn’t reach statistical significance. A subgroup of patients who didn’t respond to a cancer immunotherapy had a three-month improvement in survival, but that analysis wasn’t part of a formal statistical test.
• The setback could separate Gilead’s medicine from a rival drug developed by AstraZeneca and Daiichi Sankyo known as datopotamab deruxtecan. That medicine reduced the risk of disease progression or death by 25% in a similar trial, but hasn’t yet been proven to extend survival.

Dive Insight:

Trodelvy is one of a wave of “antibody-drug conjugates” that have been approved by regulators in recent years. These drugs combine the targeting capabilities of antibodies with a tumor-killing chemical, a profile that’s meant to be more potent and safer than older chemotherapies. They’re now coveted by large pharmaceutical companies.

Trodelvy is an example of such interest, as its potential led Gilead to pay $21 billion for its maker, Immunomedics, in 2020. While the drug has been approved for certain breast and bladder cancers, it isn’t yet a top seller. Its progress has also been overshadowed by other ADCs, most notably AstraZeneca and Daiichi’s fast-selling Enhertu.

Trodelvy is one of a few ADCs, like datopotamab deruxtecan, that target TROP2, a protein overexpressed in all types of lung cancer. The company was trying to prove Trodelvy could replace chemotherapy in one of the most common tumor types. While the outlook for people with lung cancer has improved with the arrival of immunotherapies like Merck & Co.’s Keytruda, better treatments for those who progress or don’t respond are still needed.

In Gilead’s study, EVOKE-01, the company tested Trodelvy in patients who had progressed following treatment with a platinum-based chemotherapy and an immunotherapy. Half of the 603 patients were given Trodelvy and the other half received docetaxel. Trial investigators measured whether Trodelvy could help patients live longer.

Heading into the study results, analysts had lowered expectations for Trodelvy, as datopotamab deruxtecan didn’t produce a statistically significant survival benefit in a similar trial. The drug’s benefit on tumor progression was modest, too.

Differences in the drugs and Gilead’s trial design led some industry watchers to suggest Trodelvy could produce a better result. Nonetheless, because datopotomab deruxtecan struggled to show a benefit, Trodelvy’s failure is “not totally surprising,” Jefferies analyst Michael Yee wrote in a note to clients.

Yee noted how the claimed survival benefit in those who hadn’t responded to Keytruda or similar immunotherapies was an “interesting and promising finding.” However, he wrote, “We assume [Gilead] will not be able to file this package to FDA overall.”

Gilead reported Trodelvy sales of $764 million through the first nine months of 2023, representing around one-third of the company’s oncology sales. The cell therapy Yescarta is Gilead’s top-selling cancer medicine, recording $1.1 billion through the first nine months of 2023.

Gilead shares fell as much as 11% in morning trading.

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