Study OAS · 08 July 2026

FDA Approves Vepdegestrant, First PROTAC Cancer Drug

What’s the News?

The U.S. Food and Drug Administration has approved vepdegestrant, sold under the brand name Veppanu, for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. It is significant because it is the first FDA-approved PROTAC drug, marking a shift from conventional protein inhibition to targeted protein degradation.

Vepdegestrant?

• Drug name: Vepdegestrant
• Brand name: Veppanu
• Developers: Arvinas Operations, Inc. and Pfizer Inc.
• Drug class: Oral heterobifunctional protein degrader / PROTAC therapy
• Approved for:
  • Adults with estrogen receptor-positive breast cancer.
  • HER2-negative breast cancer.
  • ESR1-mutated advanced or metastatic breast cancer.
  • Disease progression after at least one line of endocrine therapy.
• Companion diagnostic: Guardant360 CDx test to detect ESR1 mutations and identify eligible patients.

PROTAC Technology

• PROTAC stands for Proteolysis Targeting Chimera.
• It is a targeted protein degradation technology.
• Traditional drugs often work by blocking disease-causing proteins.
• PROTAC drugs work by tagging target proteins for destruction through the cell’s own protein-disposal system.
• This approach may help target proteins considered difficult to treat by conventional small-molecule inhibitors.

Clinical Trial Findings

• Approval was based on the Phase 3 VERITAC-2 trial.
• Trial design:
  • Randomised, open-label, active-controlled, multicentre trial.
  • Included 624 adults with ER-positive, HER2-negative advanced or metastatic breast cancer.
  • 270 patients had tumours carrying ESR1 mutations.
• In ESR1-mutated patients:
  • Median progression-free survival with vepdegestrant: 5 months.
  • Median progression-free survival with fulvestrant: 2.1 months.
  • Objective response rate with vepdegestrant: 19%.
  • Objective response rate with fulvestrant: 4%.

Dose and Safety

• Recommended dose: 200 mg orally once daily with food.
• Continued until:
  • Disease progression, or
  • Unacceptable toxicity.
• Key warnings:
  • QTc interval prolongation.
  • Embryo-fetal toxicity.

Additional Info

• ER-positive breast cancer
  • Cancer cells grow in response to estrogen.
  • Endocrine therapy is commonly used to block hormone-driven growth.
• HER2-negative breast cancer
  • Cancer cells do not overexpress the HER2 protein.
  • Treatment differs from HER2-positive breast cancers, where HER2-targeted drugs are used.
• ESR1 mutation
  • Mutation in the gene coding for estrogen receptor alpha.
  • Often associated with resistance to endocrine therapy.
  • Important for precision oncology and targeted treatment selection.
• Fulvestrant
  • Existing endocrine therapy used in advanced breast cancer.
  • Given as an intramuscular injection.
  • Used as the comparator in the VERITAC-2 trial.
• Precision Medicine
  • Treatment is selected based on molecular markers such as gene mutations.
  • Companion diagnostics help identify patients likely to benefit from a therapy.

Sources

• FDA
• The Hindu