- The Food and Drug Administration has approved Eisai and Merck & Co.'s Lenvima for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).
- Approval is based on data from the Phase 3 REFLECT trial, where Lenvima proved non-inferior to sorafenib, the active ingredient in Bayer's Nexavar, in extending survival among previously untreated patients. Lenvima also showed statistically significant superiority improvements in progression-free survival and objective response rate.
- Potentially serious or fatal side effects included liver toxicity, abnormally fast heart beats, excessive bleeding, among others. The most common severe side effects related to liver malfunction, in 5% or less of patients. Less severe side effects like hypertension, fatigue and diarrhea were more common.
Lenvima (lenvatinib mesylate) is a kinase inhibitor first approved in the U.S. in 2015 for recurrent or metastatic differentiated thyroid cancer, and then approved again in 2016 for second-line treatment of advanced renal cell carcinoma (RCC) in combination with everolimus. It is available in more than 50 countries worldwide.
Merck and Eisai hooked up over Lenvima in March 2018 in a deal that could be worth up to $5.76 billion. Last week's approval is the first since the collaboration was struck. The price of the drug for that indication will be around $17,000 for a month's supply, according to a report in Reuters, and forecasts predict eventual blockbuster sales.
Underscoring those estimates is the need for new treatment options for patients with HCC.
"Unresectable hepatocellular carcinoma is an extremely difficult-to-treat cancer, with no new first-line systemic therapy options for more than a decade," said Ghassan Abou-Alfa, a medical oncologist at Memorial Sloan Kettering Cancer Center, in a joint statement from Merck and Eisai. "REFLECT is the first-ever positive Phase 3 trial against an active comparator in unresectable HCC."
Lenvima is also in a Phase 2 trial as a monotherapy in biliary tract cancer and non-small cell lung cancer, and in Phase 3 in endometrial cancer.
What attracted Merck to Eisai's kinase inhibitor wasn't just the drug's potential market status, but the fact that it could be paired with Keytruda (pembrolizumab), Merck's star checkpoint inhibitor. The combo could both boost the Merck's Keytruda revenue and spread out what indications that revenue comes from. In the second quarter, Keytruda was Merck's top-selling drug at $1.67 billion, making up nearly 18% of the company's $9.3 billion in pharmaceutical sales.
Evidence supporting Keytruda and Lenvima benefits as a combo began with interim results from the Phase 1b/2 trial known as KEYNOTE-146. There, data suggested the drugs had a synergistic effect on the observed overall response rate, regardless of treatment experience or PD-L1 tumor expression in select solid tumors, including RCC and endometrial cancer.
Clinical trials are underway for Keytruda plus Lenvima in RCC, and the Food and Drug Administration has granted breakthrough therapy designation for the combo in advanced and/or metastatic RCC.
Merck and Eisai are also looking at the pairing in six types of cancer, including non-small cell lung cancer and head and neck cancer, as well as a basket trial targeting multiple cancer types.