EMA Validates Opdivo Application for Urothelial Carcinoma


On March 29, 2021, global biopharmaceutical company Bristol Myers Squibb (“BMS”) shared that its type II variation application for Opdivo (nivolumab) was validated by the European Medicines Agency (EMA). Overall, the application centered around Opdivo for the use in patients with high-risk muscle-invasive urothelial carcinoma who have undergone surgery to remove part or all of the cancer. Now, the review process for Opdivo can officially begin.


Altogether, over 35,000 patients with a variety of cancers have been treated with Opdivo. The therapy is designed to inhibit PD-1. The National Cancer Institute (NCI) describes Opdivo as:

A drug that binds to the protein PD-1 to help immune cells kill cancer cells better and is used to treat many different types of cancer. These include cancers that express the protein PD-L1 or that have certain mutations (changes) in genes involved in DNA repair.

Additionally, the NCI describes Opdivo as a monoclonal antibody – a lab-made antibody which mimics the body’s immune system. Through use, Opdivo works to promote an anti-tumor bodily response. Outside of urothelial carcinoma, Opdivo is also approved (both alone and in conjunction with other therapies) for the treatment of:

Type II Variation Application: Urothelial Carcinoma

According to the EMA, a type II variation application is:

A major change to a marketing authorisation that may have a significant impact on the quality, safety or efficacy of a medicine, but does not involve a change to the active substance, its strength or the route of administration. Type II variations require a formal approval.

In this case, the application approval hinged on data from the Phase 3 CheckMate -274 clinical trial. 709 patients enrolled. During the trial, patients received either a placebo or 240mg Opdivo every 2 weeks for up to a 1-year period. Ultimately, Opdivo was found to be relatively safe and well-tolerated. It also significantly lowered the chances of the cancer recurring, as well as lowered the mortality risk.

Opdivo Safety Information

Although Opdivo was considered relatively safe and well-tolerated, some adverse reactions did occur. These included:

  • Rashes and/or injection site reactions
  • Fatigue
  • Pruritus (intense itching)
  • Muscle and joint pain
  • Upper respiratory infections
  • Nausea and vomiting
  • Fever
  • Diarrhea or constipation
  • Appetite loss and/or unintended weight loss
  • Cough and/or shortness of breath
  • Hepatitis
  • Abdominal pain
  • Lip and mouth inflammation
  • Headache

Opdivo should not be used if you are pregnant or plan to become pregnant. It also may cause severe issues in patients who have previously been treated with allogeneic hematopoietic stem cell transplants (HSCT). Outside of the above, Opdivo may cause immune-mediated responses, such as pneumonitis, colitis, hepatitis, nephritis, and adrenal insufficiency, among others. In some cases, this was fatal for patients.

Urothelial Carcinoma

According to the Greenberg Bladder Cancer Institute:

Urothelial cancer refers to a cancer of the lining of the urinary system.  While the majority of urothelial cancers (approximately 90-95%) arise in the bladder, upper tract urothelial cancers (UTUCs) correspond to a subset of urothelial cancers that arise in the lining of the kidney (called the renal pelvis) or the ureter (the long, thin tube that connects that kidney to the bladder).

In urothelial carcinoma, the cancer begins in urothelial cells which line the bladder. This is considered one of the more common forms of bladder cancer. If identified and treated early, patients often have better outcomes. However, urothelial carcinoma has a high rate of recurrence. In fact, over half of patients treated with surgery will see cancer recurrence during their lifetime. For this reason, the prognosis for urothelial carcinoma is often not very good.

Risk factors include age (55+), being male, chemical exposure, smoking, and previous cancer treatment. Symptoms of urothelial carcinoma include:

  • Bloody or rust-colored urine
  • Frequent and/or painful urination
  • Unintended weight loss
  • Being unable to urinate
  • Appetite loss
  • Lethargy
  • Sustained back pain
  • Extreme fatigue
  • Bone pain
  • Swelling in the feet and ankles
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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