Vepdegestrant did not improve progression-free survival broadly but saw improvements in one specific patient cohort. Arvinas’ stock took a 43% tumble on the news, and analysts are downcast on the drug’s prospects.
Pfizer and Arvinas’ investigational PRTOAC degrader vepdegestrant can improve progression-free survival in breast cancer patients—but only in those carrying a specific genetic mutation.
The mixed bag comes from a topline readout of the Phase III VERITAC-2 trial released on Tuesday, comparing vepdegestrant against AstraZeneca’s Faslodex. In a press announcement, Pfizer and Arvinas reported that vepdegestrant treatment resulted in a “statistically significant and clinically meaningful” progression-free survival (PFS) improvement in patients carrying mutations in the estrogen receptor 1 (ESR1) gene.
However, in the intent-to-treat population—which encompasses all patients who were randomized in the trial—vepdegestrant did not elicit a significant improvement in PFS.
In a note to investors on Tuesday morning, analysts at BMO Capital Markets noted that vepdegestrant’s failure in the “wild type population” could limit its market opportunities down the line. “This population represents a sizable opportunity” for Arvinas and vepdegestrant, according the analysts, “representing as much as 27% of patients in the frontline setting and more moving into later lines of therapy.”
Establishing efficacy in the wild type population could have opened up approximately “$4 billion in additional revenue upside for vepdegestrant across treatment lines,” BMO continued. However, the analysts noted that after VERITAC-2’s readout, “we find it unlikely that vepdegestrant will be able to significantly tap into the upside of this wild type population.”
BMO expects Arvinas to be “meaningfully negatively impacted” by Tuesday’s data—a forecast that has at least partly already come to pass. Arvinas crashed 43% in premarket trading on Tuesday.
Nevertheless, Arvinas CEO John Houston appeared upbeat, saying in a statement that the readout “represents a significant achievement,” pointing to the potential of vepdegestrant to “provide clinically meaningful outcomes” for metastatic breast cancer patients carrying ESR1 mutations.
The magnitude of PFS improvement in patients with the ESR1 mutation with vepdegestrant “exceeded the pre-specified target” of a 40% reduction in the risk of death or disease progression, according to the release, though Pfizer and Arvinas did not provide a more specific figure for their drug candidate.
Data for overall survival had not yet matured at the time of data collection, according to the companies’ news release. VERITAC-2 will continue to follow patients to assess this outcome, one of its key secondary endpoints.
Pfizer and Arvinas will present detailed results from VERITAC-2 at an upcoming medical congress and will present these data to regulatory authorities, potentially building toward an approval for vepdegestrant, despite the uneven results.
