FDA staff question efficacy, safety of Clovis' rociletinib in T790M-positive NSCLC

In documents posted to the FDA's website Friday ahead of an advisory panel meeting on April 12, agency staff cast doubt on whether Clovis Oncology's experimental lung cancer drug rociletinib is any more effective than existing treatments. The regulator is scheduled to make a decision on whether to approve the irreversible, mutant-selective EGFR inhibitor by June 28.

FDA reviewers also recommended that rociletinib's label include a boxed warning about increased cardiovascular risk, if approved. The agency staff suggested that the labeling should include that the patient's heart be monitored while receiving treatment. Clovis has applied for rociletinib to obtain accelerated marketing approval in the US for patients with mutant EGFR non-small-cell lung cancer (NSCLC) who were previously treated with an EGFR-targeted therapy and also have the T790M mutation.

Last November, Clovis disclosed that the FDA had requested additional data for use in its efficacy analysis of two rociletinib dosage groups. The drugmaker, which had used a mix of confirmed and unconfirmed response rates to support its regulatory filing, said matured data showed that "the number of patients with an unconfirmed response who converted to a confirmed response was lower than expected." Specifically, in the intent-to-treat analysis, Clovis said confirmed response rates were 28 percent and 34 percent for the 500-mg and 625-mg doses of rociletinib, respectively.

At the time, Goldman Sachs described the disclosure as a "significant setback," while some analysts suggest rociletinib's efficacy data falls short of AstraZeneca's Tagrisso (osimertinib). The FDA granted Tagrisso accelerated approval last November for advanced NSCLC patients who carry the EGFR T790M mutation and whose disease worsened after treatment with other EGFR-blocking therapy. Tagrisso also garnered conditional approval from EU regulators earlier this year in the same indication.

Still, analyst Joshua Schimmer of Piper Jaffrey said the window for rociletinib to receive potential approval remained open given the drug's decent response rate, as well as Tagrisso's accelerated, rather than full approval. Mizuho Securities analyst Eric Criscuolo described the FDA staff review as "ugly, but we think [rociletinib] could still get approved, though timing is up in the air and its competitive position may be severely damaged."

For related analysis, see Physician Views Poll Results: EU oncologists eager for Tagrisso…if access can be secured. See also Non-Small Cell Lung Cancer: KOL Insight.

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