2. Keytruda

Merck isn't getting complacent with its mega-blockbuster Keytruda. In the last 10 months, the immuno-oncology drug has won seven FDA approvals. (FiercePharma)


Company: Merck & Co.

2020 sales: $14.38 billion

Diseases: melanoma, non-small cell lung cancer, small cell lung cancer, head and neck cancer, Hodgkin lymphoma, large B-cell lymphoma, bladder cancer, colorectal cancer, stomach cancer, esophageal cancer, cervical cancer, liver cancer, Merkel cell carcinoma, kidney cancer (in combination with Inlyta), endometrial cancer (in combination with Lenvima)

More than a decade ago, when an immune-targeted approach using monoclonal antibodies to treat cancer was first considered possible, it presented a huge opportunity for enterprising biopharma companies. Merck seized that opportunity with Keytruda, which now seems destined to become the world's top-selling drug. 

Keytruda could claim the top spot by 2023 when AbbVie’s Humira faces competition from biosimilars. Humira has been the world bestseller since 2012.

But the relatively new and rapidly changing immuno-oncology market is unpredictable, as evidenced by Bristol Myers Squibb’s Opdivo, an I-O star that has since suffered declining sales growth.

Merck has taken steps to ensure Keytruda won’t suffer the same fate. Over the last 10 months, the drug has scored seven FDA approvals.

Keytruda nabbed three of those in a 12-day span. One nod was for treating advanced cancers with a large number of genetic mutations. It was an important advance because these "tumor mutational burden-high" (TMB-H) cancers often strike children and are difficult to treat. Keytruda also gained approvals in recurrent or metastatic cutaneous squamous cell carcinoma that can’t be cured by surgery or radiation and for the first-line treatment of patients with metastatic or inoperable colorectal tumors with microsatellite instability-high or mismatch repair deficient abnormalities.

Those have been followed by approvals to treat forms of Hodgkin lymphoma and breast cancer as well as one last month to treat patients with locally advanced or metastatic esophageal or gastroesophageal junction carcinoma. 

RELATED: Merck CEO Frazier credits Keytruda’s success to slim-down strategy

But there have also been setbacks for Keytruda. Last June, the FDA gave a thumbs down to combining the drug with Eisai’s Lenvima for newly diagnosed liver cancer patients. The action came shortly after Roche’s combo of Tecentriq and Avastin was approved for the same indication based on superior survival data.

And just last month, Keytruda was dealt a pair of blows. It was pulled as an FDA-approved indication in third-line small-cell lung cancer after flunking a trial. A few weeks later, Merck received an FDA complete response letter for its application for approval of the drug in high-risk patients with early-stage triple-negative breast cancer.

RELATED: Merck, Eisai detail Keytruda and Lenvima’s endometrial cancer win in confirmatory study

Merck still has high hopes for the Keytruda-Lenvima combo, and it has scored some wins there, including a 2019 approval for certain types of endometrial carcinoma. Another approval is likely ahead for the combo in previously untreated renal cell carcinoma. 

It all adds up to the significant promise of future growth for Keytruda, but not without a lot of sweat on the part of Merck. The company continues its efforts to extend the drug's patent life through co-formulations, combinations and alternate routes of administration.

2. Keytruda