Bristol-Myers’ Opdivo Fails in Key Lung-Cancer Study; Shares Plunge, as Do Patients’ Hopes

Opdivo

A cancer drug’s surprise failure in a clinical trial erased $20 billion from Bristol-Myers Squibb Co.’s (New York City) market value Friday, and raised serious questions about one of the industry’s newest and electrifying research areas: drugs that harness the body’s immune system to fight cancer.

Bristol-Myers said its drug, Opdivo, wasn’t significantly better than chemotherapy in a study of patients with newly diagnosed lung cancer–an “unexpected” result that sent the drugmaker’s shares plummeting 16%, reports the Wall Street Journal.

Bristol-Myers had been counting on a positive result to help widen its lead in the lucrative new market for cancer immunotherapies. It also signals fresh limitations for an expensive class of drugs that has been widely expected to improve treatment of many cancers–and drive industry sales and profits for years to come.

The drugs showed impressive results in prior clinical studies in certain tumor types. In one study, about 40% of skin-cancer patients taking a similar Merck & Co. (Kenilworth NJ) drug were alive three years after starting treatment. Median survival for such patients before the advent of immunotherapy was less than a year.

In another study, kidney-cancer patients who took Opdivo had median survival of 25 months from the start of treatment, versus nearly 20 months in patients who took an older drug.

But even in those trials, many patients didn’t benefit from the immunotherapies. The failed lung-cancer study underscores the challenges in expanding immunotherapy beyond those patients who now benefit–the aim of countless companies now developing such agents.

“My take-home message is that in a minority of patients, immunotherapy is a great drug and it’s better than chemotherapy,” said Mark Socinski, executive medical director of the Florida Hospital Cancer Institute in Orlando, FL. “But that’s not true for the majority of patients, so I still think we have some work cut out for us.”

Dr. Socinski served on the steering committee overseeing the Bristol-Myers trial. Opdivo, which costs about $12,900 a month per patient, was initially approved to treat melanoma in 2014.

U.S. regulators have steadily expanded its uses to include patients whose lung cancer worsened after attempting chemotherapy, as well as patients with kidney cancer and a type of lymphoma. Many financial analysts expected Opdivo to show a benefit in patients with newly diagnosed lung cancer–a larger patient population than that for Opdivo’s other uses.

The Bristol-Myers setback could provide an opening for rival Merck. Its shares jumped 8% because, in contrast to Opdivo, Merck’s immunotherapy, Keytruda, prolonged survival in a separate study of patients with newly diagnosed lung cancer, compared with chemotherapy.

Merck hasn’t yet released the full results of that study. Keytruda also is currently approved to treat skin cancer, and lung-cancer patients who have already tried chemotherapy. On Friday, the U.S. Food and Drug Administration approved expanding Keytruda’s use to include treating patients with head and neck cancer.

Bristol’s study, called “Checkmate 026,” included 541 patients with advanced non-small cell lung cancer with no prior drug treatment. Some patients received Opdivo while others received chemotherapy.

The main goal was to demonstrate that Opdivo delayed disease progression or death compared with chemotherapy. Opdivo missed that goal, Bristol-Myers said in a news release.

The company hasn’t published the full results from the trial. Sales of Opdivo soared to $840 million in the second quarter, from $122 million from a year earlier. Those sales accounted for much of Bristol’s revenue gains in the quarter.

“Although this is disappointing in the short term, in the long term it doesn’t really change what we think about the role of immunotherapy and the combination of Opdivo and Yervoy,” Bristol-Myers CEO Giovanni Caforio said in an interview.

Bristol’s shares haven’t recovered from their swan dive last week, closing Wednesday at $60.62.

Steve’s Take: I read several news accounts of Opdivo’s catastrophe but nowhere did I see any mention of what must have been a crushing disappointment for the patients taking the treatment and their families.

Just the haircut to the company’s stock price and market cap. (By the way, Bristol-Myers market cap, post the Opdivo collapse, is a mere $101.4 billion.) The company’s marketing campaign has been a huge success with 2015 sales of $2.1 billion versus Merck’s (Kenilworth NJ) $566 million for rival treatment, Keytruda.

Begun May 16, the Bristol-Myers’ TV, print and digital Opdivo ads are updates to the original “Longer Life” campaign started last fall. I watched the 90-second television ad and tried to put myself in the place of the cancer patients whom the ad was targeting.

The new spot added the expanded indication “for previously treated advanced non-small cell lung cancer patients, regardless of PD-L1 expression,” said a Bristol-Myers spokeswoman via email interview.

While the new TV spot is similar to the original in tone and style–the use of cityscapes and white-lettered messages projected onto streets and buildings continues–it also mentions that Opdivo is now “the most prescribed immunotherapy” for this patient population and that PD-L1 testing isn’t needed.

The ad’s voiceover croons, “No biomarker testing is required with Opdivo, though physicians may choose to do so.” It’s been a key competitive advantage over Merck’s Keytruda, which does require biomarker testing to determine PD-L1 positivity.

More than 60% of new lung-cancer patients who are eligible for immunotherapy are being prescribed Opdivo, the Wall Street Journal reported in March, attributing that lack of need for PD-L1 expression as a major reason.

When asked about consumer feedback on the campaign to date, the Bristol-Myers spokeswoman said, “While it is too early to determine the overall impact of our campaign, we have been encouraged by the feedback we received from caregivers, patients and the broader healthcare community and are committed to bringing more attention to NSCLC and hope to patients and their families.”

Well, that was then. Now, I can only guess what lung-cancer patients are feeling, especially the vast majority that have not and will not respond to Opdivo. The overall five-year survival rate for people with Stage 4 lung cancer is between 1 and 5%.

Instead of a “chance of living longer,” a more candid ad would have said, “Opdivo provides a slim chance for people with advanced lung cancer to live just a few months longer.” Opdivo is still approved to treat lung cancer after a patient has undergone chemotherapy. But the drug just didn’t work as a first treatment for patients.

As reported in The New York Times, the United States and New Zealand are the only two countries in the world that permit direct-to-consumer pharmaceutical ads. Whether or not they should be banned, as the American Medical Association has argued, a much-needed, more humane requirement should be to insist that ads promoting drugs for life-threatening conditions be blunt about the outlook. At the conclusion of the incredibly heartening Opdivo ad is the uplifting tagline, “Expect More!”

Oops.