Two sBLAs Submitted for PADCEV for Urothelial Cancer

In 2007, biotechnology company Seagen Inc. and pharmaceutical company Astellas Pharma Inc. (“Astellas”) collaborated to develop enfortumab vedotin. Now, in 2021, the pair submitted two supplemental Biologics License Applications (sBLAs) for PADCEV for the treatment of urothelial cancer. The sBLAs are supported by data from the Phase 2 EV-201 and Phase 3 EV-301 clinical trials. Additionally, each sBLA serves a purpose: the first for regular approval and the second to receive a label expansion. Ultimately, the FDA will make a decision through the Real-Time Oncology Review (RTOR) pilot program, which works to get effective treatments to patients as soon and safely as they can.


First approved in 2019, PADCEV is currently approved to treat locally advanced or metastatic urothelial cancer in patients previously treated with a PD-1 or PD-L1 inhibitor. This antibody-drug conjugate (ADC) targets Nectin-4, which is highly expressed by cells in bladder cancer. The ADC Review describes ADCs as:

highly targeted biopharmaceutical drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with highly potent anti-cancer agents linked via a chemical linker.

An ideal ADC has a highly selective monoclonal antibody (mAB) for a tumor-associated antigen that has restricted or no expression on normal (healthy) cells; a potent cytotoxic agent (generally a small molecule drug with high systemic toxicity) designed to induce target cell death after being internalized in the tumor cell and released; [and] a linker that is stable in circulation, but releases the cytotoxic agent in target cells.

After binding to cells expressing Nectin-4, PADCEV release monomethyl auristatin E (MMAE). Ultimately, this stops cell proliferation and instead causes the cancerous cells to die.

EV-201 and EV-301: Treating Urothelial Cancer

In the EV-201 clinical trial, researchers evaluated PADCEV for those with urothelial cancer who had previously been treated with PD-1 or PD-L1 inhibitors, some of whom are also not eligible for cisplatin. The trial was split into 2 cohorts: those ineligible for cisplatin and those previously treated with chemotherapy. 91 patients enrolled in the cisplatin cohort. 128 patients enrolled in the chemotherapy cohort. Researchers evaluated response rate and longevity of response, efficacy, safety, tolerability, progression-free survival, and overall survival rates.

In the EV-301 clinical trial, researchers explored PADCEV as opposed to either docetaxel, vinflunine, or paclitaxel. 600 patients enrolled. This trial had similar endpoints to EV-201. Interested in the results of this clinical trial? See them published in the New England Journal of Medicine.

PADCEV Safety Information

Although PADCEV was relatively safe and well-tolerated, some adverse reactions did occur. If you receive PADCEV and experience any of the following reactions, please speak with your doctor:

  • Fatigue
  • Appetite loss
  • Rash
  • Peripheral neuropathy
  • Nausea
  • Hair loss
  • Hyperglycemia
  • Diabetic ketoacidosis
  • Blurry vision
  • Dry eyes
  • Infusion site reactions
  • Extreme itching (pruritus)
  • Urinary tract infections (UTIs)
  • Lowered lymphocyte and neutrophil counts, which may suggest neutropenia
  • Diarrhea
  • Difficulty breathing
  • Altered sense of taste

Unfortunately, PADCEV was fatal for some patients. These fatal reactions including sepsis, cardiac disorder, aspiration pneumonia, and respiratory failure.

Urothelial Cancer

According to the American Cancer Society, urothelial cancer is the most common form of bladder cancer. Typically:

These cancers start in the urothelial cells that line the inside of the bladder. Urothelial cells also line other parts of the urinary tract, such as the part of the kidney that connects to the ureter (called the renal pelvis), the ureters, and the urethra.

Risk factors include being Caucasian, being male, smoking cigarettes, having chronic urinary tract inflammation, and chemical exposure. Symptoms of urothelial cancer include:

  • Back pain
  • Frequent and/or painful urination
  • Getting up during the night many times to urinate
  • Bloody urine
  • Unintended weight loss
  • Appetite loss
  • Bone pain
  • Swelling in the lower extremities
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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