Jazz Pharmaceuticals to withdraw Zepzelca’s second-line SCLC indication after failed trial

USA— Jazz Pharmaceuticals is ending its long-running effort to keep Zepzelca (lurbinectedin) approved as a second-line treatment for small cell lung cancer (SCLC) after a confirmatory trial failed to show a survival benefit.

The company said that alongside its second-quarter earnings report, that it plans to work with the FDA to remove Zepzelca’s second-line SCLC indication from the drug’s label.

Confirmatory trial fails

The decision follows the failure of the phase 3 Lagoon trial, which did not meet its primary endpoint of overall survival.

Zepzelca monotherapy performed worse numerically than the chemotherapy regimens used in the study, while the combination of Zepzelca and irinotecan produced a numerical survival advantage that did not reach statistical significance.

However, the withdrawal will not affect Zepzelca’s first-line maintenance use in combination with Roche’s Tecentriq (atezolizumab) for patients with extensive-stage SCLC.

Zepzelca’s difficulties in second-line SCLC emerged soon after the FDA granted the drug accelerated approval for the setting.

Six months later, Zepzelca failed the randomized phase 3 Atlantis trial, which compared Zepzelca plus doxorubicin with physician’s-choice chemotherapy in previously treated SCLC.

Despite the setback, the FDA allowed Zepzelca to remain on the market.

In 2022, the agency also rejected a citizen petition seeking the drug’s withdrawal, noting that Atlantis had evaluated a lower dose of Zepzelca than the approved dose and that a significant unmet medical need remained for patients with second-line SCLC.

Competition weighs on second-line use

Since then, the treatment landscape has become more competitive. The FDA approved Amgen’s T-cell engager Imdelltra (tarlatamab) for previously treated SCLC, while the Lagoon trial evaluated standard-dose Zepzelca as a single-agent treatment.

Meanwhile, Zepzelca’s first-line maintenance approval has supported sales growth. Second-quarter revenue rose 42% year over year to $106 million, with Jazz attributing the increase entirely to first-line use.

Nevertheless, second-line treatment still accounts for most of the drug’s US sales.

About 30% to 40% of Zepzelca’s US sales now come from first-line treatment, according to Jazz chief commercial officer Sam Pearce, who spoke during an investor call on Monday.

Jazz had already been experiencing a gradual decline in second-line sales because of increasing competition.

Following the planned withdrawal, Pearce said the company expects that decline to accelerate.

Oncology withdrawals after trial failures

Jazz’s decision comes as drugmakers face increasing FDA scrutiny of medicines granted accelerated approval based on preliminary evidence.

In recent years, several cancer drugs have been withdrawn after failing required confirmatory trials.

GSK moved quickly in 2022 to withdraw its antibody-drug conjugate Blenrep (belantamab mafodotin) after the drug failed a confirmatory trial in third-line multiple myeloma.

The company later returned Blenrep to the market as part of a combination treatment after new phase 3 trials produced positive results.

Other recent oncology withdrawals following confirmatory trial failures include Takeda’s EGFR inhibitor Exkivity (mobocertinib) in lung cancer, Gilead Sciences’ antibody-drug conjugate Trodelvy (sacituzumab govitecan) in bladder cancer and Ipsen’s EZH2 inhibitor Tazverik (tazemetostat) in blood cancer.