The FDA’s Oncologic Drugs Advisory Committee (ODAC) has voted 12 to 1 in favor of requiring Clovis Oncology to finish its pivotal phase 3 study of rociletinib before the agency considers whether to approve the drug for marketing. Most of the panelists concluded that it was too early to confirm the risks and benefits of the drug, especially when potentially more-effective treatments are already on the market. The trial is expected to be completed in 2018.
Rociletinib is an epidermal growth factor receptor (EGFR) inhibitor designed to treat a subset of patients with advanced non–small-cell lung cancer (NSCLC) whose disease has worsened despite prior treatment. It targets patients with a genetic mutation known as T790M, which helps tumors evade current lung cancer therapies. A similar drug, osimertinib (Tagrisso, AstraZeneca), won accelerated approval in November 2015.
The FDA advisors said existing data on rociletinib did not adequately characterize its risk–benefit profile compared with that of current treatments, especially osimertinib, and also expressed uncertainty about the proposed dose. Further, some panel members raised questions about whether the ongoing phase 3 study of rociletinib was designed to address these concerns.
Roy Buchanan, an analyst with Janney Capital Markets, told Reuters that rociletinib is unlikely to win FDA approval, adding that he wouldn’t be surprised if Clovis retracted its application. Even if it is approved, rociletinib would likely take a back seat to osimertinib, given that its efficacy compares poorly with that of AstraZeneca’s treatment, another analyst remarked.
At the ODAC meeting, Clovis officials were questioned on why the company suddenly switched from a 500-mg dose––which was in its original new drug application last fall––to a 625-mg dose in its current phase 3 study. In February, the FDA advised Clovis that the available pharmacokinetic data did not support such a change, but Clovis amended its study anyway to concentrate on 625 mg.
In clinical trials, nearly half of the patients taking any of the doses of rociletinib experienced serious adverse events, and 17% of patients receiving the 625-mg dose died because of an adverse event. Evidence of hyperglycemia and QT prolongation (lethal heart arrhythmia) were the two leading causes of dose reductions.