In briefing documents released Wednesday, the FDA raises doubts about two AstraZeneca assets set to be discussed Friday at the agency’s first drug-related advisory committee meeting in nine months.
For the first drug-related advisory committee meeting in nine months, the FDA is asking a panel of external experts to decide whether AstraZeneca has sufficiently established clinical benefit for two of its cancer drugs. In briefing documents released Wednesday, the agency revealed some major questions about the evidence the pharma has used to back its applications.
Specifically, the regulator is seeking guidance on the oral SERD drug camizestrant—which AstraZeneca is proposing to use with a CDK4/6 blocker for HR-positive, HER2-negative breast cancer—and the AKT inhibitor Truqap, which the pharma wants to expand to metastatic hormone-sensitive prostate cancer.
The FDA’s cancer advisors will meet for a whole-day session on April 30.
“Overall, the background materials highlight fundamental issues in trial design that the agency suggests limit the validity of the results and the assessment of whether early intervention with switch therapy can drive clinical benefit,” analysts at Leerink Partners told investors in a Wednesday morning note.
Backing camizestrant is the Phase 3 SERENA-6 study, a placebo-controlled trial that focused on patients undergoing aromatase inhibitor therapy with CDK4/6 inhibition for at least six months. At the time of screening for ESR1 mutations (ESR1m), certain positive patients were randomly assigned to switch to camizestrant with CDK4/6 blockers or continue their current treatment schedule.
Results published in a June 2025 paper in The New England Journal of Medicine showed a 56% decrease in the risk of death or disease progression with AstraZeneca’s drug. Median progression-free survival (PFS) was 16 months in the camizestrant arm, versus 9.2 months in controls. Overall survival (OS) data remain immature.
Despite hitting the primary endpoint, however, the FDA raised doubts about AstraZeneca’s investigational schedule.
“The treatment paradigm evaluated in SERENA-6 is new, and currently, no drugs have FDA approval for switching treatment in patients based on detection of an ESR1m prior to radiographic progression,” the agency wrote in Wednesday’s briefing documents. “It is unclear whether changing treatment at this earlier timepoint, prior to radiographic progression, results in long-term benefit.”
The regulator also argued that “the clinical meaningfulness of the PFS improvement measured from ESR1m detection is uncertain.”
The upcoming committee meeting will also tackle AstraZeneca’s application to expand Truqap, in combination with abiraterone, to also cover metastatic hormone-sensitive prostate cancer. The pharma filed data from the Phase 3 CAPItello-281 trial, showing a 19% improvement in radiographic PFS. OS likewise remains immature.
For the Truqap application, while the FDA concedes that the study met its primary endpoint, the agency noted in a separate set of briefing documents, also released Wednesday, that the overall benefit appears small. “In the absence of a large improvement in [radiographic PFS], a statistically significant improvement in OS may be needed to support a clinically meaningful treatment effect.”
The FDA also flagged AstraZeneca’s decision to combine Truqap with an “effective and well-tolerated backbone therapy.” CAPItello-281, in this context, does not clearly delineate which treatment benefit is attributable to Truqap versus abiraterone.
When advisors gather on Friday to discuss the two applications, it will be the first time a drug-related adcomm has convened at the FDA in nine months. Such meetings have historically been used regularly at the agency, Steven Grossman, president of the regulatory consulting firm HPS Group, told BioSpace, calling them a “core component” of the FDA’s functioning and transparency.
Their recent absence, he added, highlights an “emphasis on fiat decision-making over the last year”—something he descirbes as “a counter and unwelcome change.”
