New Daily Pill for Advanced Breast Cancer After Hormone Therapy

Veppanu (vepdegestrant; Patient Information pronunciation VEP-uh-new) is an oral heterobifunctional protein degrader — a PROteolysis TArgeting Chimera (PROTAC). It binds the estrogen receptor (ER) and the E3 ligase cereblon (CRBN), tagging ER for proteasome destruction so ER protein levels fall in breast-cancer cells. That is different from simply blocking the receptor. The FDA and company materials describe it as the first FDA-approved PROTAC.

The FDA approved it on 1 May 2026 (FDA Oncology Center of Excellence notice; NDA 219835; DailyMed marketing start 05/01/2026; Initial U.S. Approval: 2026 on the USPI). The NDA applicant named on the FDA notice is Arvinas Operations, Inc. DailyMed packager / USPI distributor line: Arvinas Operations, Inc.; manufactured by Pfizer Inc. AE reporting contact on the USPI: Pfizer Inc at 1-877-702-7846. The review used Assessment Aid and finished about one month ahead of the agency goal date.

The labelled indication (USPI §1 / FDA notice):

VEPPANU is indicated for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 (ESR1)-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy.

The FDA simultaneously approved Guardant360 CDx as a companion diagnostic to identify ESR1 mutations for treatment with vepdegestrant. Select patients using ESR1 mutation(s) in a plasma specimen with an FDA-authorized test (FDA Companion Diagnostics).

Commercial availability (company claim, not the USPI distributor line): Rigel Pharmaceuticals announced on 13 August 2026 that Veppanu is available by prescription in the United States (and Puerto Rico) through its specialty distributors / specialty pharmacies, after a May 2026 exclusive global license agreement with Arvinas and Pfizer. The retrieved DailyMed / USPI still lists Arvinas as distributor and Pfizer for AE contact. Treat Rigel launch language as a company commercial claim until a revised USPI / DailyMed packager line says otherwise. No list-price or copay dollars in this article.

Where this is taking place

The pivotal trial that supports the US label is closed to new enrolment. The commercial door is a US prescription, not a trial slot.

United States — commercial labelled door. Breast / medical oncology writes a 200 mg once-daily with food prescription under the USPI when plasma ESR1 mutation testing (FDA-authorized; Guardant360 CDx named with the approval) supports the indication. Prior authorization and plan coverage still apply. Authorized ≠ funded.

VERITAC-2 — NCT05654623 — Phase 3, randomized, open-label, active-controlled, multicenter. Sponsor on CT.gov / programme materials: Pfizer (with Arvinas Estrogen Receptor funding named on the journal paper). Status commonly listed Active, not recruiting after enrolment completed. 624 adults randomized (313 vepdegestrant / 311 fulvestrant); 270 with ESR1-mutated tumours. Prior 1–2 endocrine lines including a CDK4/6 inhibitor; no prior chemotherapy for advanced/metastatic disease and no prior fulvestrant in the trial design on the label. Countries with sites included the United States, Canada, and many others on registry summaries — trial geography is not a marketing authorisation. Not an enrolment path.

Other programme studies (combination work, earlier lines) may appear on ClinicalTrials.gov later. They are not the US labelled monotherapy door described here.

Approval matrix

Access by country

• United States: Ask a breast / medical oncologist. FDA-labelled 1 May 2026 for adults with ER+/HER2−, ESR1-mutated advanced or metastatic breast cancer on an FDA-authorized plasma test, after progression following ≥1 endocrine line. Dose: 200 mg orally once daily with food. Swallow whole. ECG and electrolytes before start (do not start if QTc >470 msec). AE / product info on USPI: 1-877-702-7846 / www.VEPPANU.com; MedWatch 1-800-FDA-1088. DailyMed / Drugs@FDA host the label. No copay dollars here. Prior authorization still applies. Children not established. Rigel 13 Aug 2026 company claim: US/PR specialty distribution and RIGEL ONECARE support (833-744-3562 / www.RIGELONECARE.com) — company claim, parallel to the Arvinas/Pfizer USPI contact lines until labelling is updated.

• Canada (zoom): Not authorised on sources checked (no NOC/DIN). VERITAC-2 included Canada among covered countries on registry summaries — that is not a Canadian Product Monograph. Provincial / territorial / NIHB funding is N/A until there is a NOC. Special Access Programme supply: unknown / not confirmed. Do not mail-order a US bottle as a Canadian care plan.

• European Union / United Kingdom / Australia / Japan / China / Switzerland: Marketing authorisation unknown / not confirmed. Specialist + local named-patient / special-access only if those programmes apply in writing. Do not DIY-import.

If your regulator has not authorised it: do not import on your own.

Who is eligible (from the US label)

United States (USPI / DailyMed / FDA notice):

• Adult.
• ER-positive, HER2-negative advanced or metastatic breast cancer.
• ESR1 mutation(s) detected by an FDA-authorized test (plasma specimen; Guardant360 CDx approved with this indication).
• Disease progression following at least one line of endocrine therapy.
• Take 200 mg orally once daily with food until progression or unacceptable toxicity.
• Pivotal VERITAC-2 context (eligibility design on the label — not a hard checklist beyond the indication sentence): prior 1–2 endocrine lines including a CDK4/6 inhibitor; pre/perimenopausal women and men received a GnRH agonist; excluded prior chemotherapy for advanced/metastatic disease, prior fulvestrant, and progression within the first 6 months on the most recent endocrine line.
• Pediatrics: safety and effectiveness not established.
• Geriatrics: 39% of VERITAC-2 vepdegestrant arm ≥65; no overall safety/effectiveness differences vs younger adults called out; data ≥75 limited.
• Pregnancy: can cause fetal harm. Verify pregnancy status before start. Effective contraception for females of reproductive potential and for males with female partners of reproductive potential during treatment and for 2 weeks after the last dose.
• Lactation: do not breastfeed during treatment and for 2 weeks after the last dose.
• Infertility: may impair fertility (animal data); female effects reversible in animals.
• Contraindications: none.
• Not labelled for: ESR1-wild-type disease as the approved indication (ITT PFS in VERITAC-2 was not statistically significant on the journal/programme reports); first-line untreated metastatic disease; children.

Canada / EU / other: no retrieved national Product Monograph / SmPC to quote for eligibility. Outside the US, start with whether a regulator has authorised the product at all.

What the pivotal study showed (label vs journal)

Use the USPI / FDA notice for a US prescription conversation. Journals are supportive reading.

VERITAC-2 (NCT05654623) — FDA / USPI primary numbers (ESR1-mutated population)

• n=270 with ESR1 mutations (of 624 randomized overall). Vepdegestrant 200 mg daily vs fulvestrant 500 mg IM (Days 1 and 15 of Cycle 1, then monthly).
• Primary efficacy (BICR PFS, ESR1-mutated; USPI Table 7 / FDA notice): median PFS 5.0 months (95% CI 3.7, 7.4) vs 2.1 months (95% CI 1.9, 3.5); hazard ratio 0.57 (95% CI 0.42, 0.77); 1-sided p 0.0001.
• Confirmed ORR (BICR, measurable disease): 19% (95% CI 12, 27) vs 4% (95% CI 1.6, 10); complete responses 0% in both arms on the USPI table.
• Overall survival: immature — 16% of deaths in the ESR1-mutated population at the PFS analysis (FDA notice / USPI).
• Baseline snapshot (ESR1-mutated, USPI): median age 60; nearly all female; 68% visceral disease; 81% one prior endocrine line / 19% two; all prior CDK4/6 inhibitor; ECOG 0–1.

Overall (ITT) population: FDA/journal reports describe no statistically significant PFS difference vs fulvestrant in the full randomized set (journal HR about 0.83, p≈0.07). The labelled indication is the ESR1-mutated population.

Journal (not the label; not a preprint): Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer. N Engl J Med. DOI 10.1056/NEJMoa2505725. Simultaneously published with ASCO 2025 late-breaking presentation. Funded by Pfizer and Arvinas Estrogen Receptor; VERITAC-2 NCT05654623. Prefer USPI / FDA table language in clinic when numbers differ slightly by analysis cut.

This is a progression-free survival win in ESR1-mutated disease versus intramuscular fulvestrant — roughly three months median absolute difference on the label table — not a proven overall-survival win yet.

How it is taken (US label — keep this exact)

• Recommended dosage: 200 mg orally once daily with food.
• Swallow tablet(s) whole. Do not chew, crush, dissolve, or split. Do not take broken/cracked/damaged tablets.
• Continue until disease progression or unacceptable toxicity.
• Missed dose or vomit after a dose: take the next dose at the regular time. Do not take an extra dose the same day.
• Dose reduction for adverse reactions: 100 mg once daily. Permanently discontinue if 100 mg is not tolerated.
• Strengths: 100 mg (blue round, “VEP” / “100”) and 200 mg (blue oval, “VEP” / “200”) film-coated tablets; bottles of 30 with child-resistant closures. NDCs 84043-100-30 / 84043-200-30.
• Store 20–25 °C (excursions 15–30 °C).
• Drug-interaction dose changes (USPI): strong CYP3A inhibitors — avoid; if unavoidable on 200 mg, reduce to 100 mg (avoid strong inhibitors entirely if already on 100 mg). Strong CYP3A inducers — avoid; if unavoidable on 200 mg, increase to 300 mg (avoid if already on 100 mg). Avoid certain P-gp substrates with narrow windows; check UGT1A9 substrate labels. Avoid other QTc-prolonging drugs when possible.
• Avoid St. John’s wort, grapefruit, and grapefruit juice (Patient Information / counseling).

Companion diagnostic / ESR1 testing

Ask for ESR1 mutation testing on plasma (ctDNA) with an FDA-authorized test before treating under the US label.

• FDA contemporaneously approved Guardant360 CDx as the companion diagnostic for ESR1 mutations in breast cancer for vepdegestrant.
• USPI §2.1: select based on ESR1 mutation(s) in a plasma specimen using an FDA-authorized test. See FDA Companion Diagnostics.
• VERITAC-2 determined ESR1 status by blood ctDNA (central or local testing) for stratification; the commercial path follows the authorized-test language on the label.

If prior NGS did not report ESR1, ask whether plasma ESR1 testing can be ordered.

Safety (USPI)

Contraindications: none.

Warnings and precautions:

1. QTc interval prolongation — can raise the risk of serious arrhythmia. In VERITAC-2: QTc prolongation 10% (Grade 3 1.6%); QTc >500 msec in 1.6%; >60 msec increase from baseline in 2.6%. Correct hypokalemia and hypomagnesemia before and during treatment. ECG before start — do not initiate if QTc >470 msec. Repeat ECG about 4 weeks after start and as clinically indicated. More monitoring if congenital long QT, heart failure, electrolyte problems, or other QT-prolonging drugs. Withhold / reduce / stop per Table 2. Emergency symptoms: lightheaded/faint, dizziness, palpitations, shortness of breath, chest pain.
2. Embryo-fetal toxicity — fetal harm possible. Contraception during treatment and for 2 weeks after last dose (females; males with female partners of reproductive potential). Do not breastfeed during treatment and for 2 weeks after.

Most common (≥10%) adverse reactions including labs (USPI): decreased white blood cells, increased AST, musculoskeletal pain, fatigue, decreased hemoglobin, decreased neutrophils, increased ALT, increased alkaline phosphatase, nausea, decreased blood potassium, increased bilirubin, decreased appetite, electrocardiogram QT prolonged, decreased platelets, constipation.

Selected rates (vepdegestrant N=312 vs fulvestrant N=307): musculoskeletal pain 30% (Grade 3 2.6%); fatigue 29% (1%); nausea 14%; decreased appetite 11%; constipation 10%; ECG QT prolonged 10% (Grade 3 1.6%). Labs (all grades): WBC decreased 33%; AST increased 31%; hemoglobin decreased 24%; neutrophils decreased 23%; ALT increased 22%; alkaline phosphatase increased 21%; potassium decreased 14%; bilirubin increased 14%; platelets decreased 10%.

Serious adverse reactions 9%; permanent discontinuation 2.9%; dose interruptions 14%; dose reductions 1.9%. Fatal adverse reactions 1.0% (dyspnea, cerebral ischemia, unknown cause — one each).

Clinically relevant <10%: headache, hot flush, diarrhea, vomiting, bradycardia, urinary tract infection.

Drug interactions matter. Bring every prescription, OTC, vitamin, and herbal. Strong CYP3A inhibitors/inducers force dose changes or avoidance; P-gp and UGT1A9 substrates may need avoidance or label-directed caution; other QT-prolonging drugs need extra ECG care.

Report suspected adverse reactions to Pfizer Inc 1-877-702-7846 or FDA MedWatch 1-800-FDA-1088.

Research team (source-only)

Names and roles as they appear on primary sources — not a clinic directory.

• Arvinas Operations, Inc. (New Haven, CT on the USPI) — NDA applicant on the FDA notice; DailyMed packager / USPI distributor. NDA 219835.
• Pfizer Inc. (New York, NY) — USPI manufacturer; AE / Patient Information contact 1-877-702-7846; VERITAC-2 sponsor on ClinicalTrials.gov / programme materials.
• Arvinas Estrogen Receptor / Pfizer — funding named on the NEJM VERITAC-2 paper.
• Rigel Pharmaceuticals, Inc. — company claim exclusive global licensee (agreement announced May 2026) and US commercial availability announced 13 Aug 2026; RIGEL ONECARE 833-744-3562. Not the USPI distributor line on the retrieved DailyMed SPL.
• Guardant Health — Guardant360 CDx companion diagnostic (FDA approval with vepdegestrant).
• VERITAC-2 investigators / NEJM authors — as listed on DOI 10.1056/NEJMoa2505725 (journal byline; not reproduced as a phone directory here).
• Pfizer CT.gov / programme contact channels referenced on sponsor trial pages for NCT05654623 (trial not recruiting — not a commercial hotline substitute).

Site-level clinic phone numbers are not listed here — ask your own oncologist.

How to talk to a doctor

Bring the brand, the INN, the NCT number, the CDx, and the regulator that applies:

1. “I have ER+/HER2− advanced or metastatic breast cancer that progressed after endocrine therapy. The FDA labelled Veppanu (vepdegestrant) on 1 May 2026 as an oral PROTAC for ESR1-mutated disease. Do I have a documented ESR1 mutation on an FDA-authorized plasma test?”
2. “If ESR1 status is unknown, can we order Guardant360 CDx or another FDA-authorized ESR1 plasma test before deciding?”
3. “The USPI dose is 200 mg once daily with food. Can we plan baseline ECG and electrolytes, and confirm my QTc is not >470 msec before starting?”
4. “VERITAC-2 (NCT05654623) showed median PFS 5.0 vs 2.1 months vs fulvestrant in the ESR1-mutated group on the FDA/USPI table (HR 0.57). Overall survival was still immature. How does that fit my options versus other endocrine or chemo choices?”
5. “Side effects to watch: QTc prolongation, musculoskeletal pain, fatigue, blood-count and liver-test changes, nausea, low potassium. What is our monitoring schedule?”
6. “Please review my other medicines for strong CYP3A inhibitors/inducers, QT-prolonging drugs, and narrow-window P-gp / UGT1A9 substrates.”
7. If Canada / EU / elsewhere: “Is there a licence in this country yet? I understand US approval is not a Canadian DIN or an EU pack. I will not mail-order.”
8. “Prior authorization — what does my plan need (pathology, ESR1 report, prior endocrine / CDK4/6 history)?”

Canada zoom: not authorised on sources checked

There is no retrieved Health Canada Notice of Compliance or DIN for Veppanu / vepdegestrant on the sources used for this draft. A SUR listing for this INN was not confirmed — that is unknown, not proof of “not filed.” Until Health Canada issues an NOC and a DIN appears, Canadian public drug plans will not list it, and a US bottle is not a Canadian care plan. VERITAC-2 having included Canadian sites does not create a pharmacy product.

Bottom line

Veppanu (vepdegestrant) is the first FDA-approved PROTAC — a 200 mg once-daily with food oral ER degrader — labelled 1 May 2026 for adults with ER+/HER2−, ESR1-mutated advanced or metastatic breast cancer after ≥1 endocrine line, with ESR1 confirmed by an FDA-authorized plasma test (Guardant360 CDx). VERITAC-2 (NCT05654623) showed median PFS 5.0 vs 2.1 months versus fulvestrant in the ESR1-mutated population on the FDA/USPI table; OS immature. Main safety watch: QTc and embryo-fetal risk. Canada and other regulators: authorisation unknown / not confirmed — do not treat an unconfirmed listing as a licence. The practical door in the United States is a breast oncologist, ESR1 plasma testing, and a labelled prescription. The pivotal trial is not an enrolment path.

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Primary sources

1. FDA — FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer (1 May 2026) — https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vepdegestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast
2. FDA Prescribing Information PDF, NDA 219835, label 219835Orig1s000lbl.pdf (Issued 05/2026) — https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/219835Orig1s000lbl.pdf
3. DailyMed VEPPANU (vepdegestrant) tablets, setid 751e18d5-1d41-4b67-b1f3-10272ca5312d, packager Arvinas Operations, Inc., NDA 219835, marketing start 05/01/2026 — https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=751e18d5-1d41-4b67-b1f3-10272ca5312d
4. ClinicalTrials.gov VERITAC-2 NCT05654623 — https://clinicaltrials.gov/study/NCT05654623
5. N Engl J Med — Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer. DOI 10.1056/NEJMoa2505725 (journal; not the label; not a preprint) — https://www.nejm.org/doi/full/10.1056/NEJMoa2505725
6. FDA Companion Diagnostics index — https://www.fda.gov/CompanionDiagnostics
7. Rigel Pharmaceuticals — Rigel Announces Availability of VEPPANU (vepdegestrant) (13 Aug 2026) — company commercial claim (availability / specialty network / ONECARE); not a substitute for USPI — https://www.rigel.com/investors/news-events/press-releases/detail/445/rigel-announces-availability-of-veppanu-vepdegestrant
8. Arvinas — FDA approval press release (1 May 2026) — company announcement parallel to FDA notice — https://ir.arvinas.com/news-releases/news-release-details/arvinas-announces-fda-approval-veppanu-vepdegestrant-treatment