The researchers at the Value in Cancer Care Consortium, a nonprofit focused on cutting treatment costs for some of the most expensive drugs, set out to test whether the lower dose was just as effective — and could save patients money.
Then they learned of a new pricing strategy by Janssen and Pharmacyclics, the companies that sell Imbruvica through a partnership. Within the next three months, the companies will stop making the original 140-milligram capsule, a spokeswoman confirmed. They will instead offer tablets in four strengths — each of which has the same flat price of about $400, or triple the original cost of the pill.
Just as scientific momentum was building to test the effectiveness of lower doses, the new pricing scheme ensures dose reductions won't save patients money or erode companies' revenue from selling the drug. In fact, patients who had been doing well on a low dose of the drug would now pay more for their treatment. Those who stay on the dose equivalent to three pills a day won't see a change in price.
“That got us kind of p---ed off,” said Mark J. Ratain, an oncologist at the University of Chicago Medicine who wrote about the issue in the Cancer Letter, a publication read by oncologists. “We were just in the early stages of planning [a clinical trial] and getting it organized, and thinking about sample size and funding, and we caught wind of what the company was doing.”
Research and anecdotal experience of physicians suggests that co-pays can be a major barrier to people staying on their drugs. Stacie Dusetzina, an associate professor of cancer research at Vanderbilt University Medical Center, said that if a patient were taking one of the old capsules each day, their out-of-pocket costs under Medicare would be close to $5,000. Under the new pricing regimen, the patient's burden of the cost — for the same dosage — would roughly double. The difference in the cost to Medicare would be about $100,000. That does not reflect rebates paid by the drug company to Medicare.
“It's fascinating and disturbing,” Dusetzina said. “It appears to be a program being implemented, possibly to save some of the profits they'd be losing if dose reductions are really rapidly going to start coming down the pike.”
In a statement, Janssen and Pharmacyclics said the companies began to develop the new single-tablet dosing regimen in 2015 “as a new innovation to provide patients with a convenient one pill, once-a-day dosing regimen and improved packaging, with the intent to improve adherence to this important therapy.” They called the studies on lower dosing “highly exploratory in nature” and noted that patients who take a higher dose of the drug will save money.
But the new regimen could undermine patient safety, Ratain and colleagues argue. People on Imbruvica often need to have their doses adjusted, because it can interact with other drugs. Physicians also may try lower doses when people have trouble tolerating the drug because of side effects, such as extreme joint pain.
The companies said in their statement that a dose exchange program with rapid shipment would allow physicians to make those changes.
Under the old regimen, doctors could adjust the dose immediately by telling a patient to take one or two pills a day, instead of three, then return them to the higher dose when necessary. Under the new regimen, physicians will have to initiate a dose-switching protocol that requires paperwork. The phone number physicians have been given to call is only open Monday to Friday during business hours, several oncologists noted.
“I do share their concerns,” said Jennifer Brown, director of the Center for Chronic Lymphocytic Leukemia at the Dana-Farber Cancer Institute, who was not an author of the Cancer Letter paper. “We frequently change the dose of this drug, in relation to drug interactions in particular, and usually we need to do that basically instantaneously.”
The companies noted that the program allows physicians to make changes to dosing while following the label approved by the Food and Drug Administration. Sandy Walsh, a spokeswoman for the FDA, said the agency was aware of these concerns and is looking into them.
Complicated regimens can deter patients from sticking to their drugs — something physicians refer to as “pill burden.” But facing exorbitant prices for medication is also a barrier to a patient's adherence.
Brown said that the affordability of medication is a concern for her patients. Despite efforts to connect patients with resources to help them afford co-pays, some will request a drug that is cheaper but maybe less effective — or even push to discontinue the medicine. Ratain said that colleagues who prescribe the drug have reported that their patients do not complain about the complexity of taking three pills each day, but they have complained about the price.
“Pill-splitting is done all the time in the developing world, where these drugs are not that affordable,” Ratain said. “We're not that far from these drugs being unaffordable in the U.S.”