Gilead Sciences said even though Trodelvy missed the main goal of its Phase 3 test in non-small cell lung cancer, the drug’s preliminary results show numerical improvement in patients whose disease did not respond to prior treatment with immunotherapy. The company plans to discuss with regulators a possible path forward in these patients.

By FRANK VINLUAN

Sales for Gilead Sciences cancer drug Trodelvy are growing, but the company is counting on additional approvals to boost the product to blockbuster status and justify the premium price it paid to acquire the therapy. The drug’s failure in a pivotal lung cancer study is a setback to that strategy.

Treatment with Trodelvy, an antibody drug conjugate (ADC), fell short of a Phase 3 study’s main goal of showing statistically significant improvement in overall survival in patients with advanced cases of non-small cell lung cancer (NSCLC), Gilead announced Monday. Nevertheless, the company pointed to numerical improvements in certain patients. Gilead believes there still may be a path forward and it plans to discuss the data with regulators. The company also said it will present more detailed results at an upcoming medical meeting.

ADCs are one of the hottest areas of cancer drug research, leveraging the targeting ability of an antibody to deliver a cancer-killing drug payload directly to tumors. Trodelvy’s target is TROP-2, a protein abundant on the surface of many types of cancer cells. The drug, initially developed by Immunomedics, won its first approvals in breast cancers. The drug also has approval in certain bladder cancers. Gilead acquired Immunomedics in 2020 for $21 billion. In its most recent financial report, Gilead said Trodelvy accounted for $764 million in revenue for the nine months ending Sept. 30, 2023, a 58% increase compared to the same period in the prior year.

TROP-2 is also the target of datopotamab deruxtecan, an ADC in development by partners AstraZeneca and Daiichi Sankyo. In October, AstraZeneca reported interim Phase 3 results in NSCLC showing numerical improvement but not statistical significance compared to the chemotherapy docetaxel.

Though Gilead pointed to numerical improvement but not statistical significance for Trodelvy in its NSCLC study, the company also noted a three-month difference in median overall survival in the Trodelvy arm in a subgroup of patients whose disease did not respond to a checkpoint inhibitor. This group represents more than 60% of the clinical trial population. Though this analysis was prespecified in the clinical trial protocol, it was not powered for formal statistical analysis. In its announcement of the preliminary results, Gilead said it intends to further explore the role Trodelvy may have in treating these patients.

Leerink Partners analyst Daina Graybosch sees the silver lining for the Trodelvy results. In a note sent to investors, she said that while the failure to achieve the main trial goal is disappointing, the trending improvement in patient benefit is evidence that Trodelvy is a competitive TROP-2-targeting ADC that’s differentiated from AstraZeneca’s contender.

“We believe Trodelvy will likely have a place in the NSCLC armamentarium in a more targeted relapsed/refractory patient population, or in earlier lines in combinations,” Graybosch said.

The trending improvement Gilead reported was for both squamous and non-squamous NSCLC. By contrast, Graybosch said the benefit observed in the similarly designed study for AstraZeneca’s ADC was driven by non-squamous patients, especially those with actionable genomic alterations. She added that the Trodelvy results suggest potentially different uses for each ADC based on NSCLC subgroups. But further clarity on the Gilead drug’s competitive profile will depend on what the company reports when it presents the full clinical trial results, Graybosch said.

Photo by Gilead Sciences