Vepdegestrant

VEPPANU

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Pronunciation: vep-de-JES-trant (VEP-a-nyoo)

Vepdegestrant ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Vepdegestrant ballicule

What it isVepdegestrant (ARV-471) is an investigational oral PROTAC that recruits an E3 ubiquitin ligase to drive proteasomal degradation of the estrogen receptor.

Why this oneIt is being developed for ER-positive/HER2-negative advanced breast cancer, with the Phase 3 VERITAC-2 trial showing improved progression-free survival versus fulvestrant in ESR1-mutant patients.

What limits itIt is not yet FDA approved, and its monotherapy benefit was confined to the ESR1-mutant subgroup rather than the overall population.

Vepdegestrant molecular structure (skeletal formula) — Molecular structure: Vepdegestrant

FDA-approved for

ESR1-mutated ER+/HER2- advanced breast cancer (2026)

FDA label

Read the full label on DailyMed ↗

FDA dosing	Population	Start	Target	Max
ER-positive, HER2-negative advanced or metastatic breast cancer, ESR1-mutated (FDA-authorized plasma test)	Adults	200 mg QD with food	200 mg QD until progression or unacceptable toxicity	200 mg QD

Renal Undefined

Hepatic Undefined

Avoid strong CYP3A inhibitors and inducers; if unavoidable at 200 mg QD: reduce to 100 mg QD (inhibitor) or increase to 300 mg QD (inducer), then resume 200 mg QD after washout

Instructions

Take with food; swallow whole - do not chew, crush, dissolve, or split; do not use broken/cracked/damaged tablets
Missed dose or vomiting after a dose: skip; take next dose at the regularly scheduled time
Select patients by ESR1 mutation in plasma using an FDA-authorized test
ECG and electrolytes before initiation (do not initiate if QTc >470 ms); correct hypokalemia/hypomagnesemia; repeat ECG ~4 weeks after starting and as indicated
Adverse-reaction dose reduction: 100 mg QD; permanently discontinue if 100 mg QD not tolerated
QTc >480 ms or >60 ms above baseline: withhold until resolved, then resume per label; permanently discontinue for recurrent QTc >500 ms or torsade/serious arrhythmia

Available strengths

tab 100, 200 mg

Cautions

QTc prolongation: baseline and on-treatment ECG/electrolyte monitoring; do not initiate if QTc >470 ms; extra monitoring with congenital long QT syndrome, CHF, electrolyte abnormalities, or QT-prolonging drugs
Embryo-fetal toxicity: verify pregnancy status before starting; effective contraception (females and males with female partners) during treatment and for 2 weeks after last dose

Adverse reactions

Decreased WBC/neutrophils/hemoglobin/platelets; increased AST/ALT/ALP/bilirubin; decreased potassium
Musculoskeletal pain (30%), fatigue (29%), nausea, constipation, decreased appetite
ECG QT prolonged (10%; Grade 3 in 1.6%)

Pregnancy Can cause fetal harm (embryo-fetal mortality and structural abnormalities in rats below human exposure); verify pregnancy status before initiation

Lactation Do not breastfeed during treatment and for 2 weeks after last dose

Cost

Vepdegestrant (VEPPANU)

Strength		#/mo	generic $/mo	CostPlus
100 mg	tab	30 qd		not offered
200 mg	tab	30 qd		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Vepdegestrant is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

NO BOXED WARNINGS

Principal riskNo FDA boxed warning (investigational).

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades4 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

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