After a yearslong struggle, Jazz Pharmaceuticals has called time on Zepzelca as a second-line treatment for small cell lung cancer.
In alignment with the FDA, Jazz plans to ask the agency to remove the second-line SCLC indication from Zepzelca’s label, the company said Monday alongside its second-quarter earnings report.
The decision comes after the confirmatory phase 3 Lagoon trial recently failed on its primary endpoint of overall survival. In the study, Zepzelca (lurbinectedin) monotherapy performed even worse than other chemotherapy regimens, while a combination of Zepzelca and irinotecan showed a numerical advantage that didn’t meet statistical significance.
The withdrawal does not affect Zepzelca’s first-line maintenance approval as part of a combination with Roche’s Tecentriq for patients with extensive-stage SCLC.
Zepzelca’s troubles quickly began to show after its initial FDA go-ahead in second-line SCLC. Just half a year after the accelerated approval, the PharmaMar-partnered drug failed in the randomized phase 3 Atlantis trial, which evaluated the chemotherapy in tandem with doxorubicin versus physician’s choice of chemo in second-line SCLC.
Despite the flop, the FDA allowed Zepzelca to remain on the market and rejected a citizen petition calling for its withdrawal in 2022. At the time, the agency noted that the Atlantis study used a lower dose of Zepzelca than its approved version, and that an unmet medical need exists in second-line SCLC.
Since then, the agency has approved Amgen’s T-cell engager Imdelltra in previously treated SCLC. The Lagoon trial used standard-dose Zepzelca for its single-agent regimen.
Commercially, the first-line maintenance nod has given Zepzelca a boost. Sales of the drug in the second quarter increased 42% year over year to $106 million, as Jazz attributed the growth solely to its first-line use.
Still, second-line uses make up the majority of Zepzelca’s uptake, with around 30% to 40% of the drug’s U.S. sales coming from the first-line setting, according to Jazz’s chief commercial officer, Sam Pearce, on an investor call Monday.
Even before the withdrawal decision, Jazz already saw a gradual decline in that second-line business because of competition. Now, “we may expect that to accelerate,” Pearce said.
Cancer drugmakers have mostly been cooperative in withdrawing their drugs or indications after the FDA ramped up its post-accelerated approval scrutiny in recent years.
In 2022, GSK quickly announced plans to remove its antibody-drug conjugate Blenrep merely days after a confirmatory trial flop in third-line multiple myeloma. The British pharma managed to reintroduce the drug as part of a combination last year after new phase 3 wins.
Other oncology market withdrawals in recent years as a result of confirmatory trial setbacks include Takeda’s EGFR inhibitor Exkivity in lung cancer, Gilead’s ADC Trodelvy in bladder cancer and Ipsen’s EZH2 inhibitor Tazverik in blood cancer.