On May 1, 2026, the U.S. Food and Drug Administration approved a cancer drug that attacks tumors through a mechanism previously unavailable in clinical practice: Veppanu (active ingredient: vepdegestrant), developed by Arvinas and Pfizer, is the first approved representative of the PROTAC class, a technology that does not block cancer proteins but destroys them. For women with a specific genetic mutation for whom existing hormone therapies often fail, the drug doubled the time without disease progression in a Phase 3 trial.
What Is a PROTAC?
For decades, targeted cancer therapy was built on a single principle: a drug binds to a diseased protein and blocks its function, like a plug sealing a channel. The problem is resistance. Tumor cells can develop mutations in the protein over months that disrupt the drug's binding. The plug suddenly no longer fits.
PROTACs (Proteolysis-Targeting Chimeras) circumvent this problem through a different approach: they deliver the target protein to a cellular disposal system, the ubiquitin-proteasome system. A PROTAC molecule has two functional ends connected by a chemical bridge. One end grabs the cancer protein, the other recruits an enzyme that marks the protein as waste. The cellular machinery then completely degrades it. The protein disappears rather than merely being blocked. A further advantage: after degradation, the PROTAC molecule detaches and can repeat the same process with the next protein, increasing efficacy even at low doses.
The concept was developed around 2001 by biochemists Craig Crews at Yale University and Raymond Deshaies at Caltech. It took more than two decades of intensive research before the first compound completed clinical trials and the approval process.
Why ESR1 Mutations Were Previously Hard to Treat
Veppanu targets a specific subgroup: women with ER-positive, HER2-negative breast cancer harboring an ESR1 gene mutation. This mutation alters the estrogen receptor so that it sends growth signals even without estrogen binding. It does not arise at the outset but under the selective pressure of hormone therapies: tumor cells that develop this variant survive treatment and then multiply. Studies show that ESR1 mutations occur in 10 to 40 percent of all women with metastatic ER+/HER2- breast cancer who have already received first-line hormone therapy.
For this group, fulvestrant was previously the best available option, offering only weak protection: in the VERITAC-2 trial, the median progression-free survival with fulvestrant was 2.1 months, fewer than ten weeks without measurable worsening.
VERITAC-2 Trial Results
VERITAC-2 was a randomized Phase 3 trial with 624 participants, of whom 270 had the ESR1 mutation. In this group, Veppanu taken once daily as a tablet (200 mg) showed a median progression-free survival of 5.0 months compared with 2.1 months with fulvestrant. This corresponds to a 43 percent reduction in the risk of progression (hazard ratio 0.57), as Arvinas confirmed in the approval announcement; the results were simultaneously published in the New England Journal of Medicine. The response rate was 19 percent with Veppanu versus 4 percent with fulvestrant. The FDA granted approval one month ahead of schedule through an accelerated process. Eligible patients are women with a confirmed ESR1 mutation after at least one prior hormone therapy.
A New Class in Cancer History
How does this advance fit into the history of cancer therapy? When trastuzumab (Herceptin) was approved for HER2-positive breast cancer in 1998, it extended progression-free survival from 4.6 to 7.4 months compared with chemotherapy alone. That was considered a breakthrough that permanently changed treatment for this subgroup. Veppanu achieves a smaller absolute improvement (2.9 months), but from a baseline of just 2.1 months, for a population for which fulvestrant offered barely more than temporary stabilization.
The comparison with imatinib (Gleevec) shows the potential of targeted therapies even more clearly: when the drug was approved for chronic myeloid leukemia in 2001, fewer than 30 percent of patients survived five years without effective therapy. With imatinib, the five-year survival rate rose to around 89 percent, as a long-term study in the New England Journal of Medicine documented. Imatinib is now regarded as the template for what targeted therapy can achieve when it hits the right molecular vulnerability. Veppanu may be the beginning of a similar development for the PROTAC class as a whole.
EMA Filing and Further PROTAC Candidates
The FDA approval currently applies only to the United States. Arvinas and Pfizer have announced plans to submit applications to the European Medicines Agency (EMA) but have not named a specific date. Further PROTAC molecules targeting other cancer proteins are being tested in clinical trials, including the androgen receptor in prostate cancer and the protein BRD4, active in various tumor types. The approval of Veppanu demonstrates that the PROTAC mechanism works in real patients as predicted in basic research.