FDA Approves Merck's New-Wave Cancer Drug

FDA Approves Merck's New-Wave Cancer Drug

New Treatment, Which Costs $150,000 a Year, Is Aimed at Bolstering the Body's Immune System

U.S. regulators on Thursday approved a new kind of cancer drug from Merck & Co. that is designed to unleash the body's immune system against tumors. The drug is part of a long-anticipated wave of medicines that could transform cancer treatment and forge a large new market for pharmaceutical companies.

The Food and Drug Administration cleared the drug, pembrolizumab, for the treatment of a deadly form of skin cancer, melanoma. The approval followed a swift review of data from a relatively early-stage human trial—an unusual move reflecting the medical community's keen interest in pembrolizumab. Merck plans to sell the drug under the brand name Keytruda.

The drug comes with a steep price: Merck said the cost to payers for many patients will be $12,500 per patient monthly, or $150,000 for a year's worth of treatment.

Keytruda, an infused drug, is a new type of immunotherapy, a category of treatments that harness the immune system to fight cancer. It was approved for people who've failed to respond adequately to Yervoy, a Bristol-Myers Squibb Co. immunotherapy that works in a different fashion, and certain other drugs.

Pembrolizumab is the first so-called PD-1 inhibitor to hit the U.S. market. The drugs block a protein called programmed death receptor 1, or PD-1, which acts as a brake on certain immune-system cells to prevent them from attacking healthy tissue. Cancer cells can escape destruction by latching onto PD-1; PD-1 inhibitors block this interaction at the site of the tumor, releasing the immune system brake and allowing it to destroy the cancer. Yervoy also lifts a brake on the immune system, but does so earlier in the immune-cell activation process, which researchers say may cause more collateral destruction of normal tissue than with PD-1 blockers.

Pembrolizumab and other PD-1-targeting drugs—including those developed by Bristol-Myers and Roche Holding AG  —have generated excitement among doctors because they appear to induce relatively high rates of tumor shrinkage and prolong average survival beyond historical norms in clinical studies. Researchers say the side effects associated with the drugs appear to be manageable.

"PD-1 is truly a game-changer. It's active in a way that other drugs are not," said Lynn Schuchter, a medical oncologist who heads the melanoma program at the Abramson Cancer Center of the University of Pennsylvania and has assisted in clinical trials of the Merck drug. "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."

Some analysts believe total annual sales of cancer immunotherapies could reach about $32 billion by 2025, if more drugs make it to market to treat a range of cancers. Leerink Swann estimates Merck's new drug alone could generate annual sales of more than $6 billion by then.

A competing PD-1 inhibitor, nivolumab, hit the market in Japan this month, at a price of $143,000 for a year's worth of treatment for the average Japanese patient. The drug, from Bristol-Myers and Ono Pharmaceutical Co, is expected to be reviewed by U.S. regulators in coming months. The high price tags could fuel more debate about the affordability of new drugs.

Until a few years ago, most patients with advanced melanoma could be expected to live less than a year. Bristol's Yervoy and other drugs targeting cancer-causing genetic mutations have begun to improve the outlook. Now, Merck's pembrolizumab and similar drugs are expected to provide further advances. About 76,000 Americans are diagnosed with melanoma each year, and about 9,700 die of the disease annually, according to the American Cancer Society

This summer, researchers said about 69% of advanced melanoma patients receiving pembrolizumab in a clinical study were still alive after one year of treatment and 62% were alive at 18 months. Overall, about 34% of patients experienced tumor shrinkage of 30% or more. About 12% of patients experienced a significant adverse event such as fatigue, while 4% discontinued treatment due to an adverse event. The trial didn't have a comparator arm.

"Now I have patients coming back in significant numbers who are effectively treated with this agent, and the response is durable," said Antoni Ribas, a melanoma specialist and professor of medicine at UCLA's David Geffen School of Medicine, who served as lead investigator of the study.

Still, the Merck drug and other immunotherapies don't work in every patient and can't be considered a broad-based cure. Researchers are exploring biological markers such as the presence of certain proteins on cancer cells that may help doctors select patients most likely to benefit from a particular drug—and those less likely to benefit. Richard Pazdur, director of the FDA's office of hematology and oncology products, said finding such predictors is "an area that cries out for further attention."

Merck began testing the drug in humans in 2011 in what is known as a phase 1 study. Such studies are typically conducted in a small group of patients to test whether a drug is safe. Usually, two additional phases of studies—with larger patient populations—are needed to demonstrate a drug's efficacy and safety before the FDA will consider approving it, but sometimes the agency approves cancer drugs based on early- to midstage trials.

Dr. Ribas said he started to notice positive results relatively soon after he began overseeing pembrolizumab's testing in melanoma patients. The phase 1 study also included patients with other tumor types such as lung cancer. Merck made the unusual decision to expand and continue the phase 1 study, which eventually grew to more than 1,100 patients of various tumor types, believed to the biggest phase 1 cancer study ever.

One study participant, 59-year-old Kathleen Thomas of Redondo Beach, Calif., said she felt like she'd been given a "death sentence" when she was diagnosed with advanced melanoma in April 2011.

Her disease progressed after treatment with surgeries and drugs including Yervoy. She lost weight and strength, forcing her to use a wheelchair. Within months of joining the pembrolizumab trial in late 2012, Ms. Thomas said she began to feel better, regaining weight and using the wheelchair less often. Imaging scans have shown that her tumors have either shrunk, disappeared or remained stable, she said.

Patient interest in the Merck drug and other immunotherapies has given rise to petition drives and social-media campaigns seeking access to the drugs before regulators had approved them for sale. Such demand has fueled legislation in some states that gives terminally ill patients a "right to try" certain experimental drugs without having to go through an FDA program for early access, if a drug's manufacturer is willing. Merck started an early access program for pembrolizumab in March, but restricted it to patients whose disease had progressed after treatment with Yervoy and, if applicable, a drug targeting a genetic mutation known as BRAF.

After starting human testing in 2011, Merck raced to close the gap with rival Bristol-Myers, which introduced Yervoy in 2011 and was ahead on testing its own PD-1 inhibitor, nivolumab.

Merck got a boost in early 2013 when the FDA deemed pembrolizumab a "breakthrough therapy," a new designation that made it eligible for a speedier review and extra attention from top FDA officials. Last year, Merck's new R&D chief, Roger Perlmutter, terminated several other R&D projects and shifted resources to pembrolizumab and other promising programs.

Merck Chief Executive Kenneth C. Frazier, a company veteran since 1992, called pembrolizumab "one of the most exciting programs I've been associated with since I've been at Merck." He likened it to the company's introduction of anti-HIV medicine Crixivan in 1996, among the early protease inhibitors that helped reduce the risk of death from AIDS.

Merck said in late July it expects to have enough supply of pembrolizumab to be ready for a market launch, including meeting potential demand for "off-label" uses of the drug, which would treat a cancer type not included in the initial FDA-approved prescribing label.

More new immunotherapies could be on the horizon. Bristol-Myers expects to file by Sept. 30 for FDA approval of nivolumab as a melanoma treatment, and by year-end for approval of its use to treat lung cancer.

Bristol's drug also has generated positive clinical results, and some analysts believe the company will eventually dominate the immunotherapy market. Researchers said this summer that melanoma patients receiving a combination of Yervoy and nivolumab in a clinical trial had a median overall survival of 40 months, though many experienced significant adverse events such as the bowel disorder colitis.