September 5, 2014
By Mark Terry, BioSpace.com Breaking News Staff
Merck & Co., Inc. announced that the FDA had granted its drug Keytruda (pembrolizumab) breakthrough therapy designation. Keytruda is a treatment for advanced or unresectable melanoma that does not respond to other drugs. The drug acts by blocking a cellular pathway, PD-1 (Programmed Cell Death Protein 1). PD-1 shuts down or slows the immune response, so blocking the pathway gives the immune system a boost.
The FDA provided accelerated approval because preliminary clinical studies indicated Keytruda may provide significant improvement over other available treatments. The FDA also granted the drug priority review and orphan product designation.
In the study, 173 patients with advanced melanoma whose disease continued and progressed after earlier treatment were given Keytruda either at 2mg per kilogram or at 10 mg/kg. In the fifty percent of the study participants who received the 2 mg/kg dosage of Keytruda, tumors shrank in about 24%. The effect continued for at least 1.4 to 8.5 months, continuing further in most patients. At the 10 mg/kg dose, a similar percentage of patients’ tumors shrank as well.
A second safety trial was also performed with 411 patients with advanced melanoma. The majority of patients did not report severe immune-mediate side effects, which can affect healthy organs such as the lung, colon, glands and liver. Common side effects were fatigue, cough, nausea, itchiness, rash, decreased appetite, constipation, joint pain and diarrhea.
The drug will reportedly be quite expensive, $12,500 per patient monthly, totaling $150,000 per year. Keytruda is administered by infusion. It is the first PD-1 inhibitor to be marketed in the U.S. A few other companies, including Bristol-Myers and Roche Holding AG have drugs that target PD-1. The Bristol-Myers product is Opdivo (nivolumab), which has been distributed in Japan. It is up for review by the FDA.
Lynn Schuchter, a medical oncologist at the Abramson Cancer Center of the University of Pennsylvania who has been involved in the Merck trials, said, “PD-1 is truly a game-changer. It’s active in a way that other drugs are not. And what’s been interesting is the activity of PD-1 beyond melanoma. It looks to be active in bladder and renal and lung cancer. So this is bigger than melanoma.”
The FDA approved Keytruda under its Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review programs. “Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).”
