EMA starts review of 'transformative' bladder cancer therapy

The EMA has started a review of a regimen based on Pfizer and Astellas' Padcev and MSD's Keytruda that has been described as a game-changer in the treatment of muscle-invasive bladder cancer (MIBC).

If approved, the combination of nectin-4-directed antibody-drug conjugate (ADC) Padcev (enfortumab vedotin) and PD-1 inhibitor Keytruda (pembrolizumab) could be used as a perioperative therapy for MIBC in patients who are ineligible for chemotherapy.

The new indication has been submitted on the back of the EV-303/KEYNOTE-905 study, which tested the use of the two drugs before and after surgery to remove MIBC tumours and revealed a 60% reduction in the risk of tumour recurrence, progression, or death and a 50% reduction in the risk of death.

That result – reported at this year's ESMO cancer conference – was the first time that a neoadjuvant/adjuvant systemic treatment has improved survival in this patient group, according to the study investigators.

The start of the EU review of Padcev/Keytruda in MIBC comes just a few days after the duo were approved by the FDA for this type of bladder cancer. Padcev and Keytruda are already used to treat previously untreated patients with locally advanced or metastatic urothelial carcinoma (UC), the most common form of bladder cancer, regardless of cisplatin eligibility.

Astellas and MSD – known as Merck & Co in the US and Canada – are also running a second phase 3 trial of neoadjuvant/adjuvant Padcev/Keytruda in MIBC (EV-304/KEYNOTE-B15) in the hope of extending use into the cisplatin-eligible patient population as well.

In Europe, bladder cancer is diagnosed in over 224,000 people annually, with MIBC accounting for a "significant proportion" of cases, according to Astellas. Globally, MIBC represents approximately 30% of all bladder cancer cases.

Last year, Astellas hiked its peak sales expectations for Padcev from $2.7 billion to $3.4 billion on the promise of extending its use in bladder cancer, and there are already signs of growing momentum with the company reporting growth of 36% to JPY 103 million ($665 million) in the first half of its current fiscal year.

Meanwhile, Pfizer – which books Padcev sales in the Americas – saw 25% growth in the first nine months of 2025 to $1.43 billion.

A decision on the new MIBC indication is expected in the EU before the end of 2026.

Other options have also recently been approved for neoadjuvant/adjuvant therapy of MIBC that can be treated with surgery, including AstraZeneca's PD-L1 inhibitor Imfinzi (durvalumab) given in combination with platinum chemotherapy before surgery to remove the bladder and as a monotherapy afterwards.