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Merck’s Keytruda nabs FDA panel’s favor to line up for new bladder cancer OK


Merck & Co.’s Keytruda could soon add a new bladder cancer indication to its label, thanks to backing from a panel of FDA advisers.

Experts on the FDA’s Oncology Drugs Advisory Committee on Tuesday voted 9-4 in favor of Keytruda for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ that’s unresponsive to standard Bacillus Calmette-Guérin (BCG) therapy. 

The backing puts Keytruda on track to become the first in the PD-1/L1 class to nab an FDA approval in NMIBC by next January, ahead of rivals including Bristol-Myers Squibb’s Opdivo, Roche’s Tecentriq and AstraZeneca’s Imfinzi, all of which are also under test in similar NMIBC settings.


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The oncology experts made their decision based mainly on phase 2 complete response rate data. In the Keynote-057 study, Keytruda eliminated signs of disease in 41% of patients after three months, with responses lasting a median 16.2 months. Among them, 46% remained cancer-free at one year, according to an FDA briefing document (PDF). 

However, there were some concerns about the significance of the responses. For example, investigators reported sustained tumor clearance in 19% of all patients evaluated for efficacy after one year, below the 30% bar recommended by the International Bladder Cancer Group (IBCG), SVB Leerink analyst Daina Graybosch noted in a Wednesday report to clients.

But IBCG president and MD Anderson Cancer Center urologic oncologist Ashish Kamat came to Merck’s defense, arguing the number was calculated from a broader population not exactly identical to the one involved in the Keytruda trial and was not meant to be a hard threshold.

Some panelists also pointed out that patients’ superficial cancer, or carcinoma in situ, was identified using a less sensitive bladder scope known as white light cystoscopy, which they argued might have boosted Keytruda’s complete response rate. But given that the more accurate blue light cystoscopy is yet too expensive to be adopted widely, “the study results were said to reflect real-world experience,” according to Graybosch.

Arguments in favor of Keytruda were also made, including durable complete response rates that appeared better than those of Endo’s Valstar (valrubicin), the only drug specifically approved for BCG-unresponsive carcinoma in situ bladder cancer.

For NMIBC that doesn’t respond to BCG, the cancer could progress to invade the muscle layer of the bladder wall. To prevent further metastases, the gold standard of treatment for these patients is removal of the bladder, an invasive procedure sometimes linked to disability or even death.

Keytruda could also preserve patients’ chance to eventually opt for the risky but potentially curative procedure. According to the study, even among those who later underwent cystectomy, only 8% had advanced disease, which can complicate surgery. The rate is lower than the 20% expected from historical experience, Graybosch noted.

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

Of an estimated 81,190 new cases of bladder cancer in the U.S. in 2018, about 75% are classified as NMIBC. With that, Graybosch is projecting $250 million in peak U.S. annual sales for Keytruda in the indication, assuming the FDA follows the committee’s recommendation and grants it accelerated approval in January 2020.

Merck is currently already running the phase 3 Keynote-676 trial to confirm Keytruda’s utility in the setting. The study is testing a combination of Keytruda and BCG against BCG alone in high-risk NMIBC that’s persistent or recurrent following BCG therapy.

Other players eyeing the same market include Ferring Pharma spinout FerGene, whose gene therapy nadofaragene firadenovec is also under FDA priority review. Phase 3 results presented a few days ago showed the drug cleared tumors in 53% of BCG-unresponsive high-risk NMIBC patients, and altogether 24% of patients remained in complete response at the one-year mark.

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