Bristol-Myers Squibb Has A Cancer Breakthrough. Here’s Why It Should Cut The Price

A new cancer treatment from Bristol-Myers Squibb saved Gary McLaughlin’s life, but it also landed him in the hospital.

McLaughlin, 75, developed melanoma, the deadly skin cancer, just as he was retiring for real. He’d quit his job as a hospital administrator at 70, but spent two years helping his wife run her quilting store before they sold the business. A year after that, she noticed that a dark spot on his ear was bleeding into the pillow, and took him to the doctor. Surgeries to remove it didn’t keep the cancer from spreading to his lungs or into a large growth by his ear. It seemed certain it would kill him.

Doctors told him he was too old for a clinical trial of two Bristol-Myers Squibb drugs, Yervoy and Opdivo, until, working his hospital connections, he found one who disagreed and got him in. The tumor behind his ear shrank away, and eventually CAT scans would show that the same thing was happening in his chest. But after a celebratory trip with his daughter to Florida, he caught the flu and ended up in the hospital. Blood tests showed his kidneys had nearly quit on him, but heavy doses of steroids to suppress the immune-boosting effects of the cancer drugs pulled him through. “You don’t know anybody who is any better off than I am who has been in the hospital,” McLaughlin says. “I don’t have a lot of energy, and I have a little tremor, but I have everything to look forward to.”

Now scientists have proof that Gary McLaughlin isn’t a fluke. Today, here at the annual meeting of the American Society of Clinical Oncology in Chicago and in the New England Journal of Medicine, researchers are presenting data from a 925-patient study showing that the Yervoy-Opdivo combo was better at stopping melanoma from worsening than either Yervoy or Opdivo alone, extending the time that patients lived without their cancer advancing by seven months. But 85% of patients experienced side effects, including colitis, diarrhea, and rash. Fifty-five percent of them were severe, and 36% of patients stopped treatment as a result. Still, in a disease with few options, doctors are hailing the result – and raising questions about how to give a therapy that, in addition to its side effects, will cost at least $200,000 per patient.

Today, after the results are presented before thousands of oncologists at the ASCO meeting, McLaughlin’s doctor, Michael Atkins of the Georgetown Lombardi Cancer Center will discuss what they mean.

“I’m going to classify this as another breakthrough in melanoma therapy and probably immunotherapy as well,” Atkins says.

Breakthrough Results

A 142-patient study published by the New England Journal in April showed that the Yervoy-Opdivo combo outperformed Yervoy alone in melanoma. But this new study adds three things: it is six times larger, and therefore more reliable; it compares the combo not only to Yervoy, but to the more potent Opdivo; and it shows how different patients respond differently to the drugs depending on how their tumors do on a molecular biology test.

These factors will all play a major role in determine which patients get this combo, and in the commercial market for immune system-boosting cancer drugs. Bernstein Research estimates that Opdivo and Yervoy will generate $6.5 billion in annual sales by 2020, with Merck’s Keytruda, which is similar to Opdivo, generating another $3.5 billion.

In the new study, 58% of patients on the combo saw their tumors shrink, compared to 44% on just Opdivo and 19% on Yervoy. On progression-free survival, a common measure of how long patients go without their cancer advancing, the measures were 11.5 month for the combo, and 2.9 months for Yervoy. Side effects showed the opposite pattern: severe ones occurred to 55% of the patients in the combination group, 16% on Opdivo, and 27% on Yervoy. The study has not been run long enough to tell us which drug helps patients live longer.

But the results look very different when they are stratified by whether the tumors churned out a protein called PD-L1 (for programmed death receptor ligand one). Opdivo and Merck’s Keytruda both block PD-1, which binds to PD-L1; blocking this connection allows white blood cells to go kill tumor cells. It stands to reason that these drugs will work better when there’s a lot of PD-L1 being made.

That’s exactly what happened. When tumors had lots of PD-L1, the progression-free survival was the same whether the patient got Opdivo alone or the combo – 14 months. But in patients whose tumors were low in PD-L1, it was a different story. Patients who only received Opdivo had a progression-free survival of just 5.3 months, while for those who got the combination it was 11.2 months, a 58% decrease in the risk of disease progression.

This could be a boon for rivals like Merck and Roche, who have used PD-L1 testing as a major part of their strategy for testing their PD-1 drugs and catching up to Bristol. But both Atkins and Jedd Wolchok of Memorial Sloan Kettering, who is presenting the new results here at ASCO, argue against that interpretation – and say that they intend to give the combination to any melanoma patient who can handle the side effects.

Combo For All?

Their argument goes back to the first experiments with these drugs. When James Allison at M.D. Anderson Cancer Center was doing the first mouse experiments with what would become Yervoy, he says “the mice always progressed.” In the study that got Yervoy approved, progression-free survival was not improved compared to a control group, but patients survived, on average, four months longer.

And while the PFS rates look the same in those whose tumors have lots of PD-1, the fact is that tumors still shrank more in the patients who got the combination: 72% of patients in the combination arm responded to treatment, meaning they had significant tumor shrinkage, compared to 55% on just Opdivo and 12% on Yervoy. Atkins predicts that, when survival data are in, it will favor the combination arm, too. Also, both Wolchok and Atkins argued that patients like McLaughlin, who stop treatment but continue to benefit, will help to mitigate costs.

But there are also patients on the other extreme, who have few side effects even from the combo. One is Karen Taphorn, a 51-year-old real estate agent who is one of Wolchok’s patients. The combo caused 25 melanoma tumors that had collected in her lungs to disappear. “I was a little itchy,” she says. “That was the worst side effect that I had. I’ll take being itchy over being dead.”

There are also a lot of patients who get less dramatic benefits – in the latest clinical trial, only 11% of patients on the combo saw all of their tumors disappear. That’s down from a rosier (and probably less accurate) 22% in the earlier study.

Financial toxicity

One big problem that patients will have to face after the combo is approved will be its cost. A course of Yervoy, given in four treatments three weeks apart, costs $120,000. Opdivo, given every two weeks, is dosed by weight but for the average patient costs $150,000 a year.

The combo will actually cost less than just adding those two numbers. Lower doses of Opdivo are given, which will reduce the cost of that drug by $2,000 a month, to about $10,000. So that will be $160,000 for the initial combination treatment, followed by full-price Opdivo every two weeks afterward, with about a third of patients stopping treatment because of side effects.

For Merck and Roche, this is an opportunity: if doctors and insurers that patients with high levels of PD-L1 don’t need the combo, they can compete in that part of the melanoma market. But there’s an obvious way for Bristol to prevent this: the company could give a discount on Opdivo and Yervoy when the drugs are purchased together, thereby reducing the combo’s sky-high cost and helping to lock up the market. Will it?

“Bristol-Myers Squib does not comment on its contracting/pricing strategy,” a spokeswoman replies. “However, we consistently communicate with payers regarding the value of our medicines.”

Source: Forbes