{"entity":{"id":"vepdegestrant","kind":"drug","name":"Vepdegestrant","aka":[],"tldr":"Vepdegestrant is the first PROTAC ever approved (2026): a pill that tags the oestrogen receptor for destruction, for breast cancers with ESR1 mutations.","summary":"Vepdegestrant is a PROTAC: a heterobifunctional molecule with one end binding oestrogen receptor alpha and the other recruiting the cereblon E3 ligase, tagging the receptor for proteasomal destruction rather than simply blocking it. Taken as 200 mg once daily, it was approved in Q2 2026 for ESR1-mutated ER-positive, HER2-negative advanced breast cancer after endocrine therapy, the first PROTAC ever approved (Arvinas/Pfizer). In VERITAC-2 it improved progression-free survival versus fulvestrant to 5.0 versus 2.1 months (HR 0.57) in ESR1-mutant disease after CDK4/6 and endocrine therapy, but showed no benefit in the overall population, so the label is restricted to ESR1-mutant tumours. The absolute gain is modest, and combinations with CDK4/6 inhibitors are the next test. For a newcomer: a pill that dismantles the oestrogen receptor instead of just blocking it.","status":"approved","asOf":"2026-09-04","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Vepdegestrant"}],"tags":[],"related":[],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["protac-degrader","endocrine-therapy"],"targets":["estrogen-receptor"],"drugs":[],"companies":["arvinas","pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":["veritac-2","nct04606446","nct06206837","nct05548127","nct05909397","nct05573555"],"people":[],"bottlenecks":[],"keyPapers":["paper-protac-concept-sakamoto-pnas-2001"],"journals":[],"dependsOn":[],"notes":[],"brand":"Veppanu","code":"ARV-471","modality":"PROTAC oestrogen receptor degrader","mechanism":"Heterobifunctional molecule recruiting cereblon E3 ligase to ERα for proteasomal degradation.","approvals":[{"region":"US","year":2026,"indication":"ESR1-mutated ER+/HER2- advanced or metastatic breast cancer after endocrine therapy"}],"mechanismSteps":["Oral heterobifunctional molecule enters the tumour cell","One end binds ERα, the other recruits the cereblon E3 ubiquitin ligase","ERα is ubiquitinated and destroyed by the proteasome","The drug is released and repeats the cycle (catalytic)","ER-driven transcription stops even with ligand-independent ESR1 mutations"],"dosing":{"route":"Oral","schedule":"200 mg once daily","modifications":"Reduce for grade 3 toxicity","monitoring":"LFTs; lipids","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Fatigue"},{"event":"Nausea"},{"event":"Arthralgia"},{"event":"Hot flush"},{"event":"Transaminase increase"}],"access":[{"country":"US","reimbursement":"Medicare Part D (oral); commercial plans per formulary, often with prior authorisation","assistance":"https://www.pfizeroncologytogether.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-02","type":"designation","region":"US","note":"Fast Track designation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-06","type":"filing","region":"US","note":"NDA submitted (VERITAC-2)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-Q2","type":"approval","region":"US","note":"ESR1-mutated ER+/HER2- advanced breast cancer after endocrine therapy: first PROTAC approved","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/vepdegestrant/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"}],"technology":[{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"},{"id":"oral-serds","kind":"technology","name":"Oral SERDs","route":"/technologies/oral-serds/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"company":[{"id":"arvinas","kind":"company","name":"Arvinas","route":"/companies/arvinas/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"trial":[{"id":"nct06206837","kind":"trial","name":"A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer.","route":"/trials/nct06206837/"},{"id":"nct04606446","kind":"trial","name":"Study of PF-07248144 in Advanced or Metastatic Solid Tumors","route":"/trials/nct04606446/"},{"id":"nct05548127","kind":"trial","name":"TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study A)","route":"/trials/nct05548127/"},{"id":"nct05573555","kind":"trial","name":"TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)","route":"/trials/nct05573555/"},{"id":"nct06125522","kind":"trial","name":"TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer. (Sub-Study C)","route":"/trials/nct06125522/"},{"id":"nct05909397","kind":"trial","name":"Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole + Palbociclib in ER(+)/HER2(-) Advanced Breast Cancer","route":"/trials/nct05909397/"},{"id":"veritac-2","kind":"trial","name":"VERITAC-2","route":"/trials/veritac-2/"}],"paper":[{"id":"paper-protac-concept-sakamoto-pnas-2001","kind":"paper","name":"The first PROTAC: a chimeric molecule that tags a protein for destruction","route":"/key-papers/paper-protac-concept-sakamoto-pnas-2001/"}],"term":[{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"},{"id":"hormone-therapy","kind":"term","name":"Hormone therapy","route":"/terms/hormone-therapy/"}],"pathway":[{"id":"er-signaling","kind":"pathway","name":"Oestrogen receptor signalling","route":"/pathways/er-signaling/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"},{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}