Merck & Co. has won FDA approval for its melanoma immunotherapy Keytruda (pembrolizumab), formerly called MK-3475—the first programmed death receptor-1 (PD-1) inhibitor to be allowed for use as a drug in the U.S.
A humanized monoclonal antibody, Keytruda works by blocking interaction between PD-1 and its receptor ligands, PD-L1 and PD-L2—thus increasing the immune system’s ability to fight cancer in cells that produce the pigment responsible for color in the skin. Keytruda is indicated for patients with unresectable or metastatic melanoma and disease progression following treatment with ipilimumab and, for patients who are BRAF V600 mutation positive, a BRAF inhibitor.
Keytruda was approved at a dose of 2 mg/kg administered intravenously over 30 minutes every three weeks until disease progression or unacceptable toxicity. Keytruda’s median length of use has been estimated at 6.2 months, at a monthly cost of $12,500, about the same as other recently-approved drugs for cancer. Merck said it plans to make Keytruda available within one week from yesterday’s FDA approval.
Merck’s development of Keytruda was aided by the FDA, which granted three key designations in connection with the drug—Priority Review, granted to drugs deemed to have potential to show significant improvement in safety or effectiveness in treating a serious condition; orphan product; and Breakthrough Therapy, granted based on preliminary study findings showing the drug may offer a substantial improvement over available therapies.
FDA based its approval of Keytruda on data from the ongoing KEYNOTE-001 Phase Ib trial. The agency cited efficacy data from 173 patients with advanced melanoma whose disease progressed after prior treatment. In the half of the participants who received Keytruda at the recommended dose of 2 mg/kg, about 24% had their tumors shrink. That effect lasted at least 1.4 to 8.5 months and continued longer for most patients. A similar percentage of patients had their tumor shrink at the 10 mg/kg dose.
Merck said it continues to conduct ongoing Phase II and III clinical studies in advanced melanoma. Those studies are designed to provide further confirmatory evidence for Keytruda in the indication.
The FDA reviewed Keytruda through its Accelerated Approval program, which allows approval of new drugs for serious or life-threatening diseases based on clinical data showing the drug shows effectiveness on a surrogate endpoint that the agency considers reasonably likely to predict clinical benefit to patients.
FDA approval of Keytruda follows by a month Japan’s for the world’s first PD-1 inhibitor to win regulatory scrutiny, nivolumab, which will be marketed by Bristol-Myers Squibb (BMS) and Ono Pharmaceutical. BMS plans to file for FDA approval of the drug during the fourth quarter.
BMS is among drug developers scrambling to bring cancer immunotherapies to market—a list that includes AstraZeneca and Roche. Merck envisions numerous indications for Keytruda, and has partnered over the past year with makers of drugs that could be combined with Merck’s treatment into a combination therapy—including Amgen, Incyte, and Pfizer, as well as GlaxoSmithKline.
Just over a week ago, Pfizer expanded its research with Merck to include the combination of its Xalkori® (crizotinib) with Keytruda for anaplastic lymphoma kinase (ALK)-positive advanced or metastatic non-small cell lung cancer (NSCLC). And a day earlier on Aug. 25, Merck and Advaxis said they will launch a Phase I/II study to evaluate the safety and efficacy of Keytruda with Advaxis’ Lm-LLO cancer immunotherapy, ADXS-PSA in prostate cancer.
“Keytruda embodies Merck’s unwavering commitment to pursue breakthrough science to help people who are facing the most challenging diseases,” Kenneth C. Frazier, Merck’s chairman and CEO, said in a statement.
Keytruda is the sixth melanoma treatment approved by FDA since 2011. In addition to ipilimumab (2011), which won the agency’s nod in 2011, the other four are peginterferon alfa-2b and vemurafenib, both also approved in 2011; and dabrafenib and trametinib, both okayed last year.
“This is the latest in a string of major breakthroughs in melanoma treatment that will galvanize the field of melanoma research and cancer treatment. Pembrolizumab has demonstrated real potential to save the lives of late-stage melanoma patients who had little hope of survival just a few years ago,” said Wendy Selig, president and CEO of the Melanoma Research Alliance (MRA), in a statement. MRA is the largest private funder of melanoma research, having awarding more than $60 million toward research since its launch in 2007.
