Padcev

Padcev is used to treat muscle-invasive bladder cancer or locally advanced or metastatic urothelial cancer in combination with pembrolizumab or pembrolizumab + berahyaluronidase alfa-pmph, or alone after prior PD-1/PD-L1 inhibitor and platinum chemotherapy therapy, or for cisplatin-ineligible patients. Padcev is given via intravenous infusion by a healthcare provider as part of a cancer treatment regimen.

Padcev is FDA-approved for:

• Muscle-invasive bladder cancer (MIBC) in adults, in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, as neoadjuvant treatment, and then continued after cystectomy as adjuvant treatment
• Locally advanced or metastatic urothelial cancer (mUC) in adults in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph
• Locally advanced or mUC as a single agent in adults who:ο have previously received a programmed death receptor-1 (PD-1) orprogrammed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, orο are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.

Padcev first gained FDA approval on December 18, 2019.

Padcev is an antibody-drug conjugate combining two active components: a human antibody targeting Nectin-4 (a protein highly expressed in bladder cancer cells) and MMAE (monomethyl auristatin E), a microtubule inhibitor linked via a protease-cleavable linker.

Once Padcev binds to Nectin-4 on the surface of cancer cells, it enters the cells and releases MMAE. This mechanism of action disrupts cell division and triggers programmed cell death (apoptosis), inhibiting cancer growth.

Padcev belongs to the drug class called Nectin-4-directed antibody and microtubule inhibitor conjugates.

Before receiving Padcev, tell your healthcare provider about all of your medical conditions, including if you:

• Are currently experiencing numbness or tingling in your hands or feet
• Have a history of high blood sugar or diabetes
• Have liver problems
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

It is not known if this medicine is safe and effective in children.

Pregnancy Concerns

Padcev can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment.

• Females who can become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with Padcev. Use an effective method of birth control during your treatment and for at least 2 months after the last dose. Padcev may affect your ability to have children in the future.
• Males with a female sexual partner who can become pregnant: If your female partner is already pregnant, Padcev can harm the unborn baby. Use an effective method of birth control during treatment and for at least 4 months after the last dose of Padcev.

Breastfeeding Considerations

It is not known if Padcev passes into your breast milk. Do not breastfeed during treatment and for 3 weeks after the last dose of Padcev.

Common Side Effects of Padcev

When used in combination with pembrolizumab:

• Changes in liver function and kidney function tests
• Rash
• Increased blood sugar (glucose)
• Numbness or tingling in hands or feet
• Increased lipase (pancreas test)
• Decreased white blood cell, red blood cell, and platelet counts
• Tiredness
• Decreased sodium, phosphate, and protein (albumin) in the blood
• Itching
• Diarrhea
• Hair loss
• Decreased weight
• Decreased appetite
• Increased uric acid in the blood
• Increased or decreased potassium
• Dry eye
• Nausea
• Constipation
• Change in sense of taste
• Urinary tract infection.

When used alone:

• Increased blood sugar (glucose)
• Changes in liver and kidney function tests
• Decreased white blood cell, red blood cell, and platelet counts
• Rash
• Tiredness
• Numbness or tingling in hands or feet
• Decreased protein (albumin), sodium, and phosphate in the blood
• Hair loss
• Decreased appetite
• Diarrhea
• Nausea
• Itching
• Increased uric acid in the blood
• Dry eye
• Change in sense of taste
• Constipation
• Increased lipase (pancreas test)
• Decreased weight
• Stomach (abdominal) pain
• Dry skin

Serious Side Effects of Padcev

Severe Skin Reactions (Boxed Warning)

Severe skin reactions, including potentially life-threatening cases, have occurred with Padcev, particularly when combined with pembrolizumab. Most severe reactions occur during the first treatment cycle, but they may also happen later. Tell your healthcare provider immediately if you develop:

• Target lesions (ring-like skin reactions)
• Worsening rash or itching
• Blistering or peeling skin
• Painful sores or ulcers in the mouth, nose, throat, or genital area
• Fever or flu-like symptoms
• Swollen lymph nodes.

High Blood Sugar Levels (Hyperglycemia)

Elevated blood sugar is common with Padcev. Severe cases, including diabetic ketoacidosis (DKA) and death, have occurred in patients with and without diabetes. Contact your healthcare provider immediately if you experience:

• Frequent urination
• Increased thirst
• Blurred vision
• Confusion
• Difficulty controlling blood sugar
• Drowsiness
• Loss of appetite
• Fruity breath odor
• Nausea, vomiting, or stomach pain.

Lung Problems

Padcev may cause severe or life-threatening lung inflammation, potentially leading to death. This risk may be higher when combined with pembrolizumab. Report immediately if you develop:

• New or worsening trouble breathing
• Shortness of breath
• Cough.

Nerve Problems (Peripheral Neuropathy)

Nerve damage is common with Padcev and can be severe, particularly when combined with pembrolizumab. Contact your healthcare provider immediately if you experience:

• New or worsening numbness or tingling in hands or feet
• Muscle weakness.

Eye Problems

Eye-related issues are common during Padcev treatment. Notify your healthcare provider if you develop:

• Dry eyes
• Increased tearing
• Blurred vision
• Any vision changes.

Artificial tear substitutes can help prevent or treat dry eyes.

Leakage of Padcev Into Tissues Surrounding Infusion Site (Extravasation)

Padcev leaking from the vein into the surrounding tissue can cause reactions immediately or days after infusion. Seek medical attention if you notice:

• Redness
• Swelling
• Itching
• Blistering
• Peeling skin
• Discomfort at the infusion site.

Fertility Concerns

Padcev may cause fertility problems in both females and males, potentially affecting the ability to have children. Discuss concerns with your healthcare provider.

These are not all of the possible side effects of Padcev. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Padcev is given via an intravenous infusion into a vein by a healthcare provider.

• Padcev is given over periods of time called "cycles".
• If you receive Padcev in combination with pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex): Each treatment cycle is 21 days You will receive Padcev on days 1 and 8 of every cycle.
• If you receive Padcev alone: Each Padcev cycle is 28 days You will receive Padcev on days 1,8, and 15 of every cycle.

Your healthcare provider will decide how many treatment cycles you need and may do blood tests regularly during treatment with Padcev.

Call your doctor for instructions if you miss an appointment for your injection.

Many drugs can interact with Padcev, which may increase the risk of side effects. Tell your doctor about all your other medicines, including prescription and over-the-counter medicines, vitamins, and herbal products.

Use of Padcev together with dual P-gp and strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, ritonavir, or clarithromycin) may increase the exposure to monomethyl auristatin E (MMAE).

Active: enfortumab vedotin-ejfv

Inactive: histidine, histidine hydrochloride monohydrate, polysorbate 20, and trehalose dihydrate.

Supplied as 20 mg and 30 mg single-dose vials.

Contains no preservatives.

Manufactured and Marketed by:Astellas Pharma US, Inc.Northbrook, Illinois 60062

Distributed and Marketed by:Seagen Inc.Bothell, WA 98021U.S. License 2124

Trademark & CopyrightPadcev is a registered trademark jointly owned by Agensys, Inc. and Seagen Inc.