FDA Turns Down Withdrawal Petition for Lung Cancer Drug Approval
The FDA has rejected a citizen petition calling for withdrawal of accelerated approval for Jazz Pharmaceuticals’ and PharmaMar’s Zepzelca (lurbinectedin), a treatment for adults with metastatic small cell lung cancer (SCLC).
The petition, filed in March 2021 by the law firm Foley Hoag, requested that the FDA pull its approval of the drug after a phase 3 confirmatory trial failed to demonstrate Zepzelca plus chemotherapy’s effectiveness in prolonging overall and progression-free survival in SCLC patients.
In its rejection letter, the FDA noted that the dosage regimen studied in the phase 3 trial — lurbinectedin 2 mg/m2 every 21 days in combination with doxorubicin — is not the same as the approved dosage regimen — lurbinectedin 3.2 mg/m2 every 21 days as a single agent.
The agency added that current labeling for Zepzelca “accurately presents the monotherapy and 3.2 mg/m2 dose results in the cohort of patients with SCLC” in the study that supported the accelerated approval.
It’s not unprecedented for the FDA to allow a cancer drug’s accelerated approval to remain on the market after a failed confirmatory trial, especially when another confirmatory study has been agreed upon. For example, after a phase 3 flop, Merck & Co.’s Keytruda was able to temporarily keep its accelerated approval as a second-line liver cancer treatment pending a readout from an alternative confirmatory study. In that case, the FDA had backing from an independent advisory committee.
But this practice has raised one obvious question: Just how many chances can be afforded to an accelerated approval before a withdrawal?
“It is possible that any drug will eventually yield significant results,” University of California (UC), Irvine health policy experts David Benjamin, M.D., and Vinay Prasad, M.D., wrote in an article in The Lancet Oncology about Zepzelca’s case in May. The two researchers voiced concerns that the FDA hadn’t already revoked Zepzelca at that time.
In December 2020, however, Jazz reported that Zepzelca’s combination with doxorubicin failed to outdo physician’s choice of chemotherapy in second-line SCLC. At that time, Jazz was quick to note that the study tested Zepzelca at 2mg/m2, which is a lower dose than the FDA-approved 3.2mg/m2.
In its response to the withdrawal petition, FDA acknowledged that ATLANTIS could have satisfied the postmarketing requirement of a confirmatory trial and that its results aren’t adequate to verify Zepzelca’s benefit. But the agency disagreed that the drug should be pulled based on those results at this time.
“When a confirmatory trial does not meet its endpoint, it does not necessarily mean that the drug is not effective for the indication approved through accelerated approval,” the FDA said.
November 2, 2022
