Jazz Pharmaceuticals lung cancer drug fails phase 3 trial in fresh setback for accelerated approval
Zepzelca, the small-cell lung cancer treatment sold by Jazz Pharmaceuticals (JAZZ) and developed with Spain's PharmaMar (PHM), has failed a phase 3 trial on its primary endpoint of overall survival, threatening the drug's original accelerated approval for the second time in its history.
Jazz said on Friday that the phase 3 Lagoon trial tested Zepzelca as a monotherapy and in combination with irinotecan, marketed as Camptosar, against a control arm of topotecan or irinotecan in patients with previously treated metastatic small-cell lung cancer. All three agents used as comparators are standard chemotherapies.
The result jeopardizes an accelerated approval Zepzelca secured six years ago in second-line small-cell lung cancer, based on tumor response data from a single-arm phase 2 study. That approval had already survived one confirmatory trial failure: the phase 3 Atlantis study, which found no survival benefit for Zepzelca plus doxorubicin over physician's choice of chemotherapy. The FDA allowed the drug to remain on the market after rejecting a 2022 citizen petition seeking its withdrawal, noting that Atlantis had used a lower dose than the approved regimen and that an unmet need persisted in the setting.
In the Lagoon trial, Zepzelca monotherapy was dosed at its approved strength, while the irinotecan combination used a lower dose. Jazz said single-agent Zepzelca fared worse than the control arm, with a 19 percent higher risk of death; patients on Zepzelca alone lived a median of 8.7 months, against 10.7 months in the control group. The Zepzelca-irinotecan combination showed a modest 9.8 percent improvement in survival that fell short of statistical significance.
Jazz noted that the trial enrolled a broader population than the original phase 2 study, including patients with a history of brain metastases, and that results were more favorable in patients without such involvement. In that subgroup, Zepzelca monotherapy patients still lived a shorter median 9.6 months versus 10.7 months for control, while the combination arm reached 11.1 months, a 7.8 percent reduction in death risk.
Jazz said it has shared the data with the FDA and will discuss next steps for the second-line indication. The setback does not affect Zepzelca's separate full approval, granted in 2025, for use alongside Roche's (RHHBY) Tecentriq as first-line maintenance therapy in extensive-stage disease, where the combination cut the risk of death by 27 percent in the phase 3 IMforte trial.
Zepzelca sales rose 60 percent year-over-year to $101 million in the first quarter of 2026, driven by uptake in the first-line maintenance setting, though Jazz executives have flagged a continued decline in second-line use amid competition, including from Amgen's (AMGN) T-cell engager Imdelltra, which won traditional FDA approval in previously treated extensive-stage disease in late 2025.