Keytruda wins FDA nod to tackle early bladder cancer with gene therapy rival closely behind

Merck & Co.’s Keytruda has added a third bladder cancer use to its label.

With an FDA nod Wednesday, Keytruda has become the first PD-1/L1 inhibitor approved to treat patients with superficial but high-risk non-muscle invasive bladder cancer (NMIBC) that’s unresponsive to standard Bacillus Calmette-Guerin (BCG) treatment.

The new indication adds to Keytruda’s existing two bladder cancer nods, both in more advanced metastatic disease in which the tumor has already penetrated the muscle layer of the bladder.

Regulators at the FDA based their decision on positive results from the Keynote-057 study and followed an expert panel’s earlier recommendation in favor of an approval.

In that single-arm trial, Keytruda completely cleared signs of cancer in 41% of 96 participants who had BCG-unresponsive carcinoma in situ after three months. Among the 39 patients who reached a complete response, 18 remained cancer-free for a year or longer, as the median duration of response lasted 16.2 months after a median follow-up of 28 months.

It’s estimated that about 75% of new bladder cancer cases diagnosed in the U.S. in 2018 were NMIBC. Although BCG represents the standard first-line treatment for these early-stage patients, many cancers may not respond to it or return after initial response. Traditionally, to prevent these noninvasive cancers from progressing to the harder-to-treat metastatic form, surgical removal of the bladder is performed. However, that procedure is associated with disability, death and a negative impact on quality of life.

Now, these patients have a new option in Keytruda if they are not suitable for surgery or prefer not to have it. SVB Leerink analyst Daina Graybosch previously pegged $250 million in peak U.S. sales for Keytruda in NMIBC.

Keytruda has a few potential competitors waiting in the wings. First up, Ferring Pharmaceuticals spinout FerGene, to be led by former Ipsen chief executive David Meek, has a gene therapy dubbed nadofaragene firadenovec also under FDA priority review for the exact same indication as Keytruda’s.

RELATED: Watch out, Keytruda. Ferring's bladder cancer gene therapy rival has new data—and they look competitive

Detailed phase 3 results unveiled in December showed the drug eliminated tumors in 53%, or 55 of 103 patients, at month 3. Among them, 25 sustained a complete response for a year or longer.

Sesen Bio recently started rolling submission of its antibody-drug conjugate Vicinium, also for BCG-unresponsive NMIBC. The Cambridge, Massachusetts-based company previously showed the drug could clear cancer in 40% of 89 patients at month 3.

Other PD-1/L1 drugmakers are also eyeing the NMIBC market. Bristol-Myers Squibb is running the CheckMate 9UT study, testing its Opdivo as a monotherapy or in combination with BCG and/or its investigational IDO1 inhibitor BMS-986205 in BCG-unresponsive disease. Another newly launched trial, CheckMate 7G8, is comparing a combo of Opdivo and BCG with BCG alone in NMIBC that’s persistent or recurrent after BCG. Merck is also ahead in that setting with the Keynote-676 trial.

AstraZeneca’s Imfinzi and Roche’s Tecentriq are being tested in BCG-naïve patients.