On May 1, 2026, Arvinas and Pfizer announced that the FDA had approved Veppanu (vepdegestrant), the first PROTAC medicine ever cleared in the United States. The decision came ahead of the June 5 date the agency had set for its ruling.
The approval is narrow, and the label says so. Veppanu is for adults whose breast cancer is estrogen receptor-positive, HER2-negative, advanced or metastatic, and carries an ESR1 mutation, confirmed by an FDA-authorized test, and that kept growing despite at least a first round of endocrine treatment.
What a PROTAC does
Most cancer drugs sit on a target protein and switch it off. A PROTAC removes it. Nature Reviews Drug Discovery described the class as one that degrades its targets rather than inhibiting them, and said the approval highlights the surge of interest in targeted protein degradation. Here the target is the estrogen receptor that drives many of these tumors. Randy Teel, Arvinas’s chief executive, called the approval “a transformative moment” and said the company had pioneered the technology since 2013.
The need is concrete. Among patients given endocrine therapy together with a CDK4/6 inhibitor, the companies said, up to 40-50% carry ESR1 mutations, and those mutations drive resistance. “There have been minimal second-line treatment options once standard therapies are no longer effective,” said Dr. Erika Hamilton of the Sarah Cannon Research Institute, a principal investigator on the pivotal trial.
The trial record
The evidence comes from VERITAC-2, a randomized, open-label phase 3 trial that enrolled 624 patients at 213 sites in 25 countries and set vepdegestrant against fulvestrant. Of those patients, 270 had ESR1 mutations. In that group median progression-free survival was 5 months on vepdegestrant and 2.1 months on fulvestrant, a 43% lower risk of progression or death (hazard ratio 0.57). OncLive reported that the 6-month progression-free rate was 45.2% against 22.7%, and that tumors responded in 18.6% of patients on the new drug versus 4.0% on fulvestrant.
The result did not carry over to everyone. Across the full trial population, median progression-free survival was 3.7 months on vepdegestrant and 3.6 months on fulvestrant (hazard ratio 0.83, P = .07), which is why the approval is limited to the mutated subgroup. Overall survival data were immature, with 16% of deaths in the ESR1 group at the time of the progression analysis.
Most adverse events were low grade. Among the common ones the company listed were fatigue, nausea, musculoskeletal pain, and QT prolongation on an electrocardiogram. OncLive noted that adverse events were more frequent with vepdegestrant than with the comparator.
A pill against an injection
The route of delivery separates the two arms. Vepdegestrant is a 200 mg tablet taken once a day. Fulvestrant is an intramuscular injection: twice in the first 28-day cycle, on days 1 and 15, and once at the start of each cycle afterward.
Rigel Pharmaceuticals later took on the drug under a licensing agreement with Arvinas and Pfizer, a change Nature added to its report on May 12, 2026. Rigel announced on Aug. 11, 2026 that Veppanu could now be prescribed across the country.
Sources
- First PROTAC gains FDA approval, bolstering targeted protein degradation and induced proximity ambitions (Nature Reviews Drug Discovery)
- Arvinas Announces FDA Approval of VEPPANU (vepdegestrant) for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer
- FDA Accepts NDA for Vepdegestrant in ESR1-Mutated, ER+/HER2- Breast Cancer (OncLive)
- Rigel Announces Availability of VEPPANU (vepdegestrant)
