Written by Jane Xia and Michael L. Fuller

The U.S. Food and Drug Administration (FDA) recently approved Keytruda (pembrolizumab) for treatment of patients whose cancers have a specific genetic feature (biomarker). The FDA has traditionally approved cancer treatments based on where in the body the cancer started—for example, the lung or breast. This is the first time a drug was approved based on a genetic feature of the tumor, without regard to the tumor’s originating location in the body.

Keytruda, which is marketed by Merck & Co., belongs to a new class of drugs called PD-1/PD-L1 inhibitors that help the immune system fight cancer by blocking a mechanism tumors use to evade detection. The approved indication is for treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). MSI-H and dMMR positive tumors contain abnormalities that affect the proper repair of DNA inside the cell. Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places.

In September 2014, Keytruda became the first in a new class of checkpoint inhibitors to receive FDA approval. Since then, the agency has approved Keytruda for the treatment of certain patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma. In 2016, Keytruda was approved in Japan for the treatment of certain patients with PD-L1-positive unresectable advanced/recurrent non-small cell lung cancer; and the European Commission has also approved Keytruda for patients with locally advanced or metastatic non-small cell lung cancer in patients whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. The worldwide sales for Keytruda in 2016 were $483 million, a 125% increase from 2015.

On Merck’s website, the company identifies this drug as associated with its rights in U.S. Patents 8,354,509 and 8,900,587, both related to antibodies and compositions containing antibodies which bind to human PD-1. Keytruda has been the subject of several patent lawsuits. In 2014, Bristol-Myers Squibb Co. and Ono Pharmaceutical Co. Ltd. filed patent infringement suits against Merck in the U.S., some EU countries, Australia, and Japan, claiming Merck's drug infringed their patents covering the use of antibodies which bind to the PD-1 drug target. In January 2017, Merck entered into a settlement and license agreement with Bristol-Myers and Ono to resolve all global patent-infringement litigation. Merck agreed to pay Bristol-Myers and Ono an initial payment of $625 million as well as a 6.5 percent royalty rate on Keytruda sales from January 2017 to December 2023 and a 2.5 percent rate for the subsequent three years. In April 2017, Merck also settled the patent infringement lawsuit with PDL Biopharma Inc. and agreed to pay $19.5M for a fully paid-up, royalty free, non-exclusive license to PDL’s U.S. Patent 5,693,761, as well as an agreement not to sue Merck for royalties regarding Keytruda.