Takeda to Withdraw Lung Cancer Drug After Failed Confirmatory Study

The Japanese pharmaceutical giant Takeda has announced that its treatment for EGFR exon 20 insertion-mutated lung cancer, Exkivity (mobocertinib), received accelerated approval in 2021 and will be withdrawn because it failed to achieve the expected results in the confirmatory study required by that approval.

Accelerated approval offers a way to bring drugs to patients more quickly for diseases with limited treatment options. However, this fast track carries the possibility that the FDA (United States Food and Drug Administration) will withdraw regulatory approval—unless the company withdraws the drug first. Takeda has decided to do exactly that with its lung cancer drug Exkivity.

Following discussions with the FDA, Takeda decided to withdraw Exkivity voluntarily. Exkivity treats non-small cell lung cancer (NSCLC) by targeting epidermal growth factor (EGFR). The EGFR protein must have exon 20 mutations, a genetic feature also targeted by Johnson & Johnson's Rybrevant (amivantamab). Takeda's capsule formulation offered the advantage of oral administration over Rybrevant, which is given by infusion. Both drugs received accelerated approval in 2021 based on open-label studies.

Both drugs received accelerated FDA approval based on their objective response rates:

• In CHRYSALIS, the objective response rate among patients receiving Rybrevant was 40%.
• In a single-arm phase 1/2 clinical study, Exkivity had an objective response rate of 28%.

A drug granted accelerated approval must confirm its safety and efficacy in a postmarketing study. In July 2023, when Takeda announced its financial results for the first quarter of fiscal 2023, the company said that Exkivity's phase 3 confirmatory study had been stopped for futility. The announcement of the voluntary withdrawal gave no details of the study results, but Takeda said the full data would be presented at an upcoming oncology meeting or in a peer-reviewed journal.

Meanwhile, J&J applied to the FDA for full approval of Rybrevant. In July, the company announced positive results from the phase 3 PAPILLON study, which evaluated Rybrevant (amivantamab-vmjw) combined with chemotherapy (carboplatin-pemetrexed) as first-line treatment for advanced NSCLC.

While withdrawing Exkivity in the United States, Takeda also plans to withdraw it voluntarily from other markets where it is approved. Not all withdrawals are so orderly and timely.