FDA OKs Merck's Keytruda to Treat Cancers With Genetic Defects -- Update

The U.S. Food and Drug Administration on Tuesday approved Merck & Co.'s Keytruda drug to treat tumors with a certain genetic defect -- the first time the agency has cleared a cancer drug for a use not tied to the site of a tumor.

The FDA approved Keytruda to treat advanced solid tumors with genetic defects known as "microsatellite instability" or "mismatch repair" deficiencies. A study showed the drug shrank tumors in a significant number of patients with colorectal and 14 other cancer types that had the genetic defect.

Merck's Keytruda, which works by harnessing the body's immune system to attack tumors, has previously been approved to treat several site-specific tumors, including those of the skin and lung.

Write to Peter Loftus at peter.loftus@wsj.com

The U.S. Food and Drug Administration on Tuesday approved Merck & Co.'s Keytruda drug to treat tumors with a certain genetic defect -- the first time the agency has cleared a cancer drug for a use not tied to the site of a tumor.

The FDA approved Keytruda to treat tumors with genetic defects known as "microsatellite instability" or "mismatch repair" deficiencies, which are present in an estimated 4% of cancers. Studies showed the drug shrank tumors in a significant number of patients with colorectal and 14 other cancer types that had the genetic defect.

The FDA's action -- its first "site-agnostic" approval for a cancer drug -- signals a potential shift in cancer treatment. For decades, cancer drugs have typically been approved and used to treat site-specific tumors like those of the brain or breast.

With the site-agnostic approach, "instead of the classical way of treating patients based on their tumor type, you treat based on a genetic alteration," said Bert Vogelstein, co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center. Dr. Vogelstein's research linked mismatch-repair defects to cancer in the 1990s.

The approach holds promise to improve treatment for patients whose tumors have less common molecular traits, and who might not benefit from standard treatments approved for specific tumor sites. But it also requires additional tests of tumor samples to find patients with the right genetic fit.

Tests for "mismatch repair" typically cost between $300 and $600, according to Johns Hopkins. Dr. Vogelstein said the cost is minor compared with other costs for cancer care.

Merck's Keytruda costs about $13,000 a month per patient. The drug, which works by harnessing the body's immune system to attack tumors, has previously been approved to treat several site-specific tumors such as those of the skin and lung. Last year Keytruda generated global sales of $1.4 billion.

Other drugs are being developed for "site-agnostic" uses in tumors with particular genetic or molecular traits, regardless of where they are in the body. Loxo Oncology Inc., of Stamford, Conn., is developing a drug targeting certain proteins that contribute to tumor-cell growth in many cancers. If clinical studies are successful the company may seek an FDA approval of the drug for use in any tumor that has the proteins.

The new FDA approval allows Keytruda's use in tumors with the genetic defect that have progressed following prior treatment with other drugs, and have no satisfactory alternative treatment options.

The FDA action was based on results from five clinical trials totaling nearly 150 patients with the genetic defect. More than half had colorectal cancer and the rest had 14 different cancer types. Nearly 40% of patients experienced significant tumor shrinkage, according to the FDA. Side effects included fatigue and diarrhea. Because of how it works, Keytruda also can cause immune-mediated side effects like colitis.

John Shinnick, 75 years old, of Barnegat, N.J., was diagnosed with pancreatic cancer in April 2015. He underwent surgery followed by chemotherapy and radiation, but the cancer began to advance again last year. A test determined that his tumor had microsatellite instability, and in June 2016 he enrolled in a clinical trial of Keytruda at Hopkins. He said the drug has been effective for him, and he is due to continue taking it until June 2018.

"I'm ecstatic with the results," he said.

Write to Peter Loftus at peter.loftus@wsj.com

(END) Dow Jones Newswires

May 23, 2017 18:35 ET (22:35 GMT)