Veppanu

Veppanu is used to treat estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced breast cancer or breast cancer that has spread to other parts of the body (metastatic), and whose disease has progressed after at least one line of endocrine-based therapy. Veppanu is taken once daily with food.

• Your healthcare provider will perform a test to make sure that Veppanu is right for you.

Veppanu (vepdegestrant) is the first PROTAC (PROteolysis TArgeting Chimera) therapy to be approved and works by degrading the estrogen receptor, halting breast cancer cell growth.

Veppanu (vepdegestrant) received FDA approval on May 1, 2026, based on Phase 3 VERITAC-2 clinical trial (NCT05654623) data showing a 43% reduction in disease progression risk versus fulvestrant in ESR1-mutant breast cancer (median PFS: 5 vs 2.1 months). Adverse events were predominantly low-grade and included decreased blood cell counts, nausea, and fatigue. It is not yet known when Veppanu will be available for patient use.

Take Veppanu exactly as your healthcare provider tells you. Do not change your dose or stop taking Veppanu unless your healthcare provider tells you.

• Take Veppanu 1 time each day.
• Take Veppanu with food.
• Swallow Veppanu tablets whole. Do not chew, crush, dissolve, or split the tablets before swallowing.
• Do not take Veppanu tablets that are broken, cracked, or look damaged.

If you miss a dose or vomit after taking Veppanu, do not take another dose of Veppanu on that day. Take your next dose the following day at your regularly scheduled time. Do not take 2 doses on the next treatment day.

Veppanu (vepdegestrant) is a targeted protein degrader designed to eliminate the estrogen receptor (ER), a key driver of breast cancer growth. It works by simultaneously binding to two proteins: the estrogen receptor and an intracellular enzyme called cereblon (CRBN). This dual binding triggers a cellular "tagging" process that marks ER for destruction. The cell's natural waste-disposal system, the proteasome, then degrades the tagged receptor, significantly reducing ER levels within breast cancer cells.

Vepdegestrant is effective against both normal (wild-type) and mutated forms of ER, including ESR1 mutations, which are commonly associated with resistance to existing hormonal therapies. In preclinical studies, it successfully halted ER-driven cancer cell proliferation in laboratory models and demonstrated meaningful antitumor activity in animal models of both wild-type and mutant ESR1 breast cancer.

Veppanu (vepdegestrant) belongs to the drug class called heterobifunctional protein degraders, and is the first in its class to be developed, a technology Arvinas has pioneered since 2013.

Avoid taking St. John’s wort, eating grapefruit, or drinking grapefruit juice during treatment with Veppanu.

Before taking Veppanu, tell your healthcare provider about all of your medical conditions, including if you:

• Have heart failure or heart rhythm problems, including QTc prolongation, and long QTc syndrome
• Have low blood levels of potassium or magnesium
• Are pregnant or plan to become pregnant. Veppanu can harm your unborn baby.
• Are breastfeeding or plan to breastfeed.

It is not known if Veppanu is safe and effective in children.

Pregnancy

Veppanu can harm your unborn baby. Females who can become pregnant:

o Your healthcare provider may do a pregnancy test before you start treatment with Veppanu.

o Use effective birth control (contraception) during treatment with Veppanu and for 2 weeks after the last dose.

o Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Veppanu.

Males with female partners who can become pregnant:

• Use effective birth control (contraception) during treatment with Veppanu and for 2 weeks after the last dose.

Breastfeeding

It is not known if Veppanu passes into your breast milk. Do not breastfeed during treatment with Veppanu and for 2 weeks after the last dose.

Common Side Effects

The most common side effects of Veppanu are:

• Decreased white blood cell counts
• Increased liver function tests
• Muscle and bone pain
• Tiredness
• Decreased red blood cell counts
• Nausea
• Decreased potassium levels in your blood
• Decreased appetite
• Abnormal electrocardiogram (QT prolonged)
• Decreased platelet counts
• Constipation.

Serious Side Effects

Veppanu can cause serious side effects, including:

• Heart rhythm problems (QTc interval prolongation). Veppanu can cause changes in the electrical activity of your heart and may increase your risk of abnormal heart rhythm problems and sudden death. Your healthcare provider will check your heart with a test called an electrocardiogram (ECG) and check your blood potassium and magnesium levels before and as needed during treatment with Veppanu. Get emergency medical help right away if you get any signs and symptoms of abnormal heart rhythm, including:

o Feeling lightheaded or faint

o Dizziness

o Feeling that your heart is pounding or beating fast (heart palpitations)

o Shortness of breath

o Chest pain.

Your healthcare provider may decrease your dose, temporarily stop, or completely stop treatment with Veppanu, if you develop certain side effects.

• Fertility problems. Veppanu may affect fertility in males and in females who can become pregnant. Talk to your healthcare provider if this is a concern for you.

These are not all of the possible side effects of Veppanu.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially ask your healthcare provider if you take:

• Strong CYP3A Inhibitors, such as itraconazole, clarithromycin, or voriconazole. Concomitant use should be avoided. If unavoidable, your healthcare provider may need to reduce your Veppanu dose
• Strong CYP3A Inducers, such as rifampin, phenytoin, or carbamazepine. Concomitant use should be avoided. If unavoidable, your healthcare provider may need to increase your Veppanu dose
• Certain P-gp Substrates, such as digoxin or colchicine. Avoid concomitant use with narrow therapeutic index P-gp substrates where even small increases in drug concentration may result in serious adverse reactions.
• Certain UGT1A9 Substrates, such as mycophenolate or propofol. For concomitant use with UGT1A9 substrates where minimal concentration increases may lead to serious adverse reactions, refer to the Veppanu Prescribing Information for guidance.

Veppanu and other medicines may affect the way they work and may cause serious side effects. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.

Store Veppanu at room temperature between 68˚F to 77˚F (20˚C to 25˚C).

Veppanu comes in a bottle with a child-resistant closure. Keep it in its original container.

Keep Veppanu and all medicines out of the reach of children.

Active ingredient: vepdegestrant

Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose monohydrate, microcrystalline cellulose, sodium stearyl fumarate, vitamin E-polyethylene glycol succinate, and Opadry® QX Blue that consists of FD&C Blue No. 2 (indigo carmine) aluminum lake, ferric oxide yellow (yellow iron oxide), ferrosoferric oxide (black iron oxide), glyceryl mono and dicaprylocaprate (glycerol monocaprylocaprate), polyvinyl alcohol, polyvinyl alcohol, polyethylene glycol graft copolymer [macrogol poly (vinyl alcohol) grafted copolymer], talc, and titanium dioxide.

Veppanu (vepdegestrant) was discovered by Arvinas and co-developed with Pfizer. Both companies are working together to identify a third-party commercial partner best positioned to bring Veppanu to market effectively.