“Failed to Improve Survival” — Jazz’s Zepzelca to Exit Second-Line Lung Cancer Market

Jazz Pharmaceuticals has decided to voluntarily withdraw the indication for Zepzelca as a second-line treatment for small cell lung cancer (SCLC).

On the 4th (local time), Jazz Pharmaceuticals said during its second-quarter earnings report that it plans to consult with the US Food and Drug Administration (FDA) and request removal of Zepzelca (ingredient: lurbinectedin) from the approved labeling for second-line treatment of small cell lung cancer. The decision follows the failure of a confirmatory phase 3 trial.

In the recently reported confirmatory phase 3 LAGOON study, Zepzelca failed to improve overall survival (OS), the primary endpoint. Zepzelca monotherapy produced poorer results than the control arm’s other chemotherapy regimens, while the combination therapy with irinotecan also failed to achieve statistical significance.

Zepzelca’s second-line treatment journey has not been smooth. Just 6 months after receiving accelerated approval in 2020, it failed another confirmatory trial, ATLANTIS. At the time, the FDA allowed the product to remain on the market, citing the high unmet medical need in the second-line treatment setting and the fact that the Zepzelca dose used in the trial was lower than the approved dose.

The withdrawal will not affect Zepzelca’s indication for first-line maintenance therapy. Zepzelca is approved and used in combination with Roche’s Tecentriq as first-line maintenance therapy for patients with extensive-stage small cell lung cancer.

Commercially, Zepzelca has shown growth, driven by its entry into the first-line maintenance therapy market. Second-quarter sales this year were $106 million (approximately 159 billion won), up 42% from the same period a year earlier, and the company said the growth was entirely attributable to first-line treatment use.

However, 60% to 70% of Zepzelca’s US sales still come from the second-line treatment market. Sam Pearce, Jazz’s chief commercial officer (CCO), said, “The second-line treatment business had been gradually declining because of competition, and this withdrawal decision could accelerate the decline.”

As the FDA has recently strengthened postapproval reviews of drugs granted accelerated approval, cases of cancer drugs that failed confirmatory trials being removed from the market have continued to emerge. GSK’s Blenrep, Takeda’s Exkivity and Gilead’s Trodelvy have had indications withdrawn for similar reasons.