Merck - Keytruda - WSJ

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According to Bernstein Research, Wall Street analysts forecast 2023 Keytruda sales of $11.3 billion, and 2023 Opdivo sales of $9.7 billion.

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For Cancer Drugs, Will Monday's Data Be As Good As It Gets?

Matthew Herper
Apr 13, 2018 @ 12:57 PM

Helen Hunt and Jack Nicholson in a scene from the film 'As Good as It Gets', 1997. (Photo by TriStar Pictures/Getty Images)
At one point in James Brooks' 1997 comedy As Good As It Gets, Jack Nicholson, playing a misanthropic New York novelist with obsessive compulsive disorder, exits his psychiatrist's office and asks those assembled in the waiting room, "What if this is as good as it gets?"

Nicholson won an Oscar for that, so I guess I shouldn't feel too bad about wanting to ask the same thing of scientists and drug companies who are developing cancer drugs that harness the immune system. On Monday, much-awaited details on two studies of these new medicines, expected to become among the drug industry's best sellers, will be presented at the annual meeting of the American Association for Cancer Research. One study will show that Merck's Keytruda, combined with chemotherapy, helps lung cancer patients live longer. And another will show that in patients whose tumors have lots of genetic mutation, combining Bristol-Myers Squibb's Opdivo, a drug very similar to Keytruda, with another Bristol immunotherapy, Yervoy, slows tumor growth in lung cancer. Wall Street analysts and doctors alike want to know how much so they can figure out how these medicines should be used.

Already, these are revolutionary treatments. They are also expensive. Keytruda and Opdivo cost $150,000 a year each. The Yervoy-Opdivo combination can cost $256,000 per year in melanoma, where it is approved, but most patients benefit less and so also cost less to treat. So here's a third complication to think about: are there better cancer immunotherapies waiting just around the corner, which can either be added to these medicines? Or are these, as Nicholson's character put it, as good as it gets?

For drug companies, the idea that even better drugs are always coming down the pike is part of the story they sell investors and policymakers. But it's often a long way between one innovation and another, and a first breakthrough in cancer does not guarantee a second. The cancer drug cisplatin, for instance, revolutionized cancer treatment in the 1980s, curing many patients with testicular cancer including the cyclist Lance Armstrong. In 1981, the Washington Post called it "a success in the search for miracle drugs," but that didn't mean more such drugs were found. In the 1990s, the discovery of Taxol, originally made from the bark of a yew tree, helped many patients with breast and ovarian cancer. There was not a flood of much better Taxol-like drugs, despite the efforts of drug companies.

And then there is the example of gene-targeted cancer therapy, starting with Gleevec. In 2001, this Novartis leukemia pill was on the cover of Time. There was a new weapon in the war against cancer, and Gleevec pills were the bullets, Time said. "Is this the breakthrough we've been waiting for?" Gleevec did turn some types of leukemia into a chronic disease, and there have been many, many more gene-targeted drugs. But few have proven as effective at keeping cancer in check as Gleevec has, and most of those took more than another decade to emerge. So asking if there are going to be more immunotherapy innovations means asking something else: Could this time be different? Again, is this the breakthrough we've been waiting for?

Last week, there was a good indication that maybe it isn't. Merck and a smaller biotechnology company, Incyte, had collaborated on testing Keytruda with Incyte's experimental drug, epacadostat. The drug sought to target a pathway, hijacked by cancer cells, that the developing fetus uses to protect itself against its mothers immune system. It made scientific sense to combine the two drugs, but the companies revealed last week that it did not help patients. Patients who received the combination had their cancer advance at exactly the same rate as those who got Keytruda alone. What's more, patients who got the combo were 13% more likely to die, though those results were far from statistically significant.

Roger Perlmutter, Merck's head of R&D, says that the important thing to remember is that epacadostat's big advantage was that it seemed to have no safety penalty. It had appeared effective, but had never before been studied in a control group. He says, going forward, that maybe it would be better to focus on drugs that have some benefit alone (epacadostat didn't) but will be synergistic together. Then, to make me feel like a dour doomsayer, he continues that "if you want to take the optimistic view," one would see that already we have two classes of immunotherapy drugs – Yervoy, and then Keytruda and Opdivo, both known as PD-1 inhibitors. And that's actually a lot better than the previous instances I mentioned. "As you're pointing out, getting to the next one may be tricky."

When it comes to developing a next immunotherapy drug, Bristol has a distinct advantage: it's head of cancer research, Nils Lonberg, who led the way in developing the previous immunotherapies. Still, the drug business is littered with examples of amazing innovators who couldn't come up with a second – never mind third – hit.

Fouad Namouni, Bristol's oncology development head, points to Bristol's collaboration with Nektar Therapeutics on a drug meant to further prime immune cells to attack cancer, and also to the company's purchase of a company called IFM Therapeutics to try and make immunotherapy more effective in types of cancer where it doesn't work. "I think we're well-positioned to generate, at a certain point of time, I don't know when, another breakthrough," Namouni says.

According to Bernstein Research, Wall Street analysts forecast 2023 Keytruda sales of $11.3 billion, and 2023 Opdivo sales of $9.7 billion. Roche and AstraZeneca, which have competing drugs, will have to settle for $3 billion each.

One big wild card? Whether any company can beat history, and invent or buy another cancer immunotherapy drug.