SERENA-4 was assessing AstraZeneca’s Etcamah as a first-line option for certain patients with advanced breast cancer—a setting that could have meant a $2.9 billion opportunity for the drug.
Just days after crossing the FDA finish line for a separate indication, AstraZeneca’s oral SERD drug Etcamah failed to show improvement in progression-free survival in a Phase 3 study—potentially pushing a larger opportunity out of reach.
In the Phase 3 SERENA-4 study, Etcamah was being tested in combination with Pfizer’s CDK4/6 blocker Ibrance as a frontline treatment for patients with ER+, HER2- advanced breast cancer. Comparators were given Ibrance plus the aromatase inhibitor anastrozole. While investigators observed a numerical improvement in the trial’s primary endpoint of progression-free survival (PFS), the result was statistically significant, according to a Friday announcement.
Leerink analysts had been looking forward to SERENA-4, writing in a Sept. 5 note that a positive outcome could open “a significantly larger opportunity” for Etcamah. The firm doubled down on this assessment in a Sept. 12 note issued after the study’s failure, though analysts conceded it had always been a long shot.
“While the 1L SERENA-4 trial constituted a larger opportunity, it was also high-risk, high-reward,” Leerink said, noting that the firm had attributed only a 20% chance of success to the study. The analysts project peak Etcamah sales to hit $830 million, down from their previous unadjusted $2.9 billion estimate had SERENA-4 succeeded.
AstraZeneca continues to advance Etcamah in a comprehensive development program in early breast cancer. This includes CAMBRIA-1 and CAMBRIA-2, Phase 3 trials that span around 10,000 patients who are at intermediate and high risk of recurrence, the pharma said on Friday. CAMBRIA-1 is expected to read out in the first half of 2027, according to Leerink.
SERENA-4’s failure comes just days after the FDA granted accelerated approval to Etcamah’s use in patients with HR+/HER2- breast cancer who also carry ESR1 mutations, as detected during aromatase inhibitor and CDK4/6 inhibitor therapy. Etcamah is indicated to be used with a CDK4/6 inhibitor like Pfizer’s Ibrance, Eli Lilly’s Verzenio or Novartis’ Kisqali.
The FDA approved Etcamah based on the Phase 3 SERENA-6 study, which documented a significant 56% decrease in the risk of disease progression or death—the trial’s primary endpoint—versus controls on standard of care. The FDA’s verdict marked a key victory for AstraZeneca after an advisory committee in April voted 6-3 against an approval due to issues with the study design. Still, with only SERENA-6’s data in its label, Etcamah will likely achieve only “modest revenues,” Leerink said in its Sept. 5 note.
