The approval opens up a “modest” market for AstraZeneca’s Etcamah, according to Leerink analysts, who nevertheless looked forward to an upcoming late-stage readout that could lead to a “significantly larger opportunity” for the drug.
The FDA has signed off on AstraZeneca’s camizestrant for certain patients with breast cancer despite an independent expert panel in April voting against the drug. Camizestrant will be sold under the brand name Etcamah.
Etcamah, an oral SERD, is indicated for patients with HR+/HER2- advanced breast cancer in whom ESR1 mutations (ESR1m) are detected during aromatase inhibitor and CDK4/6 inhibitor therapy. The drug is intended to be used in combination with a CDK4/6 blocker such as Eli Lilly’s Verzenio, Pfizer’s Ibrance and Novartis’ Kisqali, according to a news release on Friday.
The FDA’s verdict contrasts with the outcome of an advisory committee meeting in May, during which an independent panel of experts voted 6-3 against an approval, pointing to issues with how AstraZeneca designed its pivotal late-stage SERENA-6 study.
In the trial, patients were switched to an Etcamah regimen or designated to continue their current treatments during testing for ESR1 mutations. This is a relatively early switch point, which normally occurs upon disease progression, the panelists argued at the time. An approval based on SERENA-6 could encourage other companies to similarly push up their switch points for targeted therapies—but some experts felt AstraZeneca’s evidence was too thin to back such a precedent.
“The data for changing the paradigm just isn’t there,” Stanley Lipkowitz, deputy director of the Center for Cancer Research at the National Cancer Institute, said at the time to explain his no vote. “If there were an OS [overall survival] benefit, I would have voted yes.”
Panelists were asked whether, based on SERENA-6, a clinically meaningful benefit was demonstrated in this patient subset.
Indeed, while overall survival data for Etcamah remain immature, the clinical benefits in SERENA-6 were enough to elicit an approval from the FDA. Patients in the Etcamah arm saw a significant 56% reduction in the risk of death or disease progression as compared to controls on standard of care, according to AstraZeneca’s Friday announcement. Time to second progression was also significantly longer in those on Etcamah.
For Leerink Partners, the approval based on SERENA-6 opens “modest revenues” for Etcamah of around $750 million. Clinicians consulted by the firm “have highlighted that SERENA-6 did not definitively answer whether treating [at the point of] ESR1m emergence ahead of radiographic progression is beneficial versus treating on progression,” the analyst said in a Saturday note.
Leerink is looking ahead to a readout for the Phase 3 SERENA-4 study, however. This trial is positioning the Etcamah regimen as a first-line option, which could open up a “significantly larger opportunity” for the drug, bumping up peak revenue projections to approximately $2.9 billion, according to the analysts. Data from SERENA-4 are expected in the second half of this year.
