Merck gets partial thumbs-down on Keytruda in lymphoma from NICE cost-effectiveness watchdogs

NICE quibbled with Merck's methodology for demonstrating the cost effectiveness of Keytruda in treating Hodgkin lymphoma patients who have failed other treatments. (Merck & Co.)

Just one week after England's National Institute for Health and Care Excellence (NICE) said no to Gilead’s CAR-T treatment Yescarta in non-Hodgkin lymphoma, it has decided that Merck’s blockbuster checkpoint inhibitor, Keytruda, is not a good treatment choice in Hodgkin lymphoma—at least not for all patients.

NICE published a guidance document on Monday suggesting that Keytruda should not be used in patients with relapsed or refractory Hodgkin lymphoma who have already been treated with both the chemotherapy drug Adcetris and an autologous stem cell transplant. It did recommend the drug for use on its Cancer Drugs Fund in patients who are not eligible for stem cell transplant.

The reason for the split decision? NICE said it currently recommends Bristol-Myers Squibb’s rival checkpoint inhibitor, Opdivo, for treating relapsed or refractory Hodgkin lymphoma after Adcetris and stem cell transplant. Physicians suggested to NICE that the cost-effectiveness of Keytruda (pembrolizumab) would likely be similar to that of Opdivo (nivolumab), but Merck did not provide head-to-head data in patients who had received stem cell transplants, according to the decision.

“The committee noted that the company had not provided evidence to demonstrate different clinical efficacy between nivolumab and pembrolizumab, or provided a convincing explanation as to why the treatment effects would be likely to differ,” the agency wrote.

Merck did not immediately respond to a request for comment from FiercePharma. Keytruda is approved in the U.K. as a solo therapy in patients with Hodgkin lymphoma who have either failed stem cell transplant or are ineligible for it.

The company provided economic models for Keytruda in Hodgkin lymphoma patients who had failed stem cell transplants, but NICE found them to be faulty. Merck’s package for NICE included data from a trial showing an improvement in progression-free survival and objective response rate in both subsets of patients, but it wasn’t clear how big an effect it was. The company also initially forecast that stem cell transplants would happen 12 weeks after patients started their treatments—an inappropriate assumption, NICE said, because the effort to find stem cell donors almost always causes a delay in the procedure.

So Merck revised the model, assuming that all transplants would happen 24 weeks after treatment. NICE quibbled with the company’s methodology, though, ultimately deciding that conclusions about overall survival benefits from Keytruda in patients undergoing stem cell transplants were “likely to have been overestimated in the model,” the guidance document said.

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The exclusion of Keytruda after stem cell transplant from the NHS' list of covered drugs could dampen what has been an impressive run from Merck in the ongoing rivalry with BMS. In the second quarter, Keytruda hauled in $1.67 billion in total sales, surpassing Opdivo’s $1.63 billion in sales in the same period. It was the first time Keytruda beat Opdivo in the market for PD-1/L1 inhibitors.

Merck has scored some key wins for Keytruda that are helping fuel its strong run. In August, for example, the FDA expanded the drug’s label to say that when it is combined with Eli Lilly’s Alimta and platinum chemo in patients with treatment-naïve non-small cell lung cancer, it cuts the risk of death by 50% over chemo alone. Merck has the distinction of having the only checkpoint inhibitor that's approved in the U.S. in the first-line lung cancer setting. And in July, the European Medicines Agency’s (EMA) recommended the combo, too.

Just how big an effect the NICE rejection in Hodgkin’s lymphoma will have on Keytruda remains to be seen. But one thing can be said for certain: England's cost-effectiveness watchdogs are clearly not welcoming the pricey new generation of immuno-oncology treatments with open arms. That was evident in NICE’s rejection of Yescarta, which came immediately after the personalized cell therapy was approved in Europe to treat relapsing diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma.

NICE didn’t disclose Gilead’s planned price of Yescarta in the U.K., saying only that the product lacks “plausible potential to be cost-effective.” Gilead is in discussions with the agency and hopes to reach an agreement that will reverse the decision.