Merck touts a confirmatory Keytruda win for liver cancer as 'dangling' accelerated approval saga marches on
Accelerated approval for Merck’s Keytruda in a common form of liver cancer looked tenuous after a confirmatory study whiffed on two survival measures. But after ODAC recommended to keep the drug on the market back in April, the pharma giant said Monday another trial has brought better tidings.
The blockbuster PD-1 met its primary endpoint in statistically significant overall survival compared to placebo, Merck announced Monday morning, in a study evaluating Keytruda plus chemotherapy in 453 hepatocellular carcinoma patients from Asia. Though Merck didn’t report any specific figures, the company noted Keytruda also hit secondary endpoints for progression-free survival and objective response rate.
“Frequently diagnosed at an advanced stage, hepatocellular carcinoma has one of the highest mortality rates of solid cancers,” Merck Research Laboratories VP Scot Ebbinghaus said in a statement. “[W]e look forward to engaging with regulatory authorities as quickly as possible.”
Hepatocellular carcinoma was among a group of cancer indications in which Keytruda had nabbed an accelerated OK examined by the Oncologic Drugs Advisory Committee across a three-day span in April. Even though the drug missed the earlier study’s dual primary endpoints, ODAC voted unanimously 8-0 to keep Keytruda on the market as a second-line treatment for HCC.
Merck and the FDA went back and forth at the adcomm, with Merck asserting the Keytruda regimen was still necessary for second-line patients despite a recent approval for a Tecentriq-Avastin combo in first-line HCC. Richard Finn, a professor of medicine at UCLA and paid consultant for Merck, said at the time that pulling the HCC approval didn’t make sense given Monday’s study had been expected to read out within a few months.
As such, the new trial essentially functioned as a second confirmatory study after the adcomm discussions. Had the new trial proven negative, it’s unclear whether ODAC or the FDA would remain as lenient as in the April hearing.
Keytruda has already run into some headwinds over its stable of accelerated approvals this year, after flopping several confirmatory studies. It also met a rare regulatory rebuke in a major indication. In March, the FDA issued a CRL to the best-selling drug after Merck went against regulators’ wishes in submitting its data package too early. But Merck returned later in the year and scored a full, first-line approval in July.
Also during the April ODAC marathon, panelists recommended against keeping Keytruda’s accelerated OK in third-line stomach cancer, an indication where Merck subsequently pulled the drug in July. The move came after Bristol Myers Squibb won full approval for Opdivo in the first-line setting. FDA officials highlighting how the changing treatment landscape swayed their thinking.
Merck saw more straightforward success in bladder cancer, with Keytruda earning a narrow 5-3 ODAC vote to stay on the market. The FDA extended full approval for first-line treatment here last month.