SAN DIEGO -- Two well-known rheumatologists took on the almost literally $64,000 question in rheumatology in 2017: whether or not patients taking one of the long-time standard biologic drugs such as infliximab (Remicade) or adalimumab (Humira) should switch to one of the growing number of biosimilar agents now available.
In a "Great Debate" held at the , what once seemed like it would be a no-brainer now has many, perhaps most clinicians wondering whether there is any point to it.
Speaking for the "yes, switch" position, Jonathan Kay, MD, of the University of Massachusetts ľֱ School in Worcester, made a good case that biosimilars really are close copies of the originator product, thanks to the rigorous approval process required by U.S. and European regulators. And, he contended, smashing the monopolies held by makers of originator drugs can't help but drive prices down.
His opponent, Roy Fleischmann, MD, of the University of Texas Southwestern Medical Center in Dallas, sought with some success to poke holes in Kay's review of the efficacy-and-safety literature. He argued convincingly, for example, that was underpowered to prove that switching maintains efficacy and safety reliably in all approved indications.
But Fleischmann appeared to land the real knockout blow by arguing that the most important reason to prescribe biosimilars -- their ostensibly lower cost -- simply doesn't exist in the United States.
Although a snafu with the giant exhibition hall's electronic voting system made it uncertain who "won," it was hard to find an attendee afterward who sided with Kay.
Similarity Well Proven
The least debatable point Kay made was that biosimilars are well proven to be reasonable facsimiles of the originators. He showed slide after slide of the many comparisons made during the course of their approvals. Some of the most telling were those, for infliximab and adalimumab, demonstrating that batches of the same originator products were less alike than each was to the biosimilar.
In particular, a comparison of U.S.- and European-sourced Remicade showed they were "essentially biosimilars of one another," with slightly but noticeably different functional characteristics such as strength of target binding.
Kay's main argument was that all biological products vary considerably from batch to batch, and often from year to year. Biologics are, by definition, produced from living organisms and thus subject to variation because of small differences in growth conditions and extraction processes. As well, manufacturers may change their manufacturing methods over time -- with approval from regulatory authorities -- which also change the products' characteristics.
Biosimilars are like another batch of the original branded product, he said.
He also cited several studies that have been conducted in patients switching from an originator biologic to a biosimilar, and in some cases back again. For the most part, these studies -- some blinded, some not -- have shown no important efficacy differences or safety signals for switching.
When questions were raised, they were in unblinded studies (for example, in a Danish study following patients taking etanercept [Enbrel] who were mandated by the country's national health system to switch en masse to a biosimilar). Patient complaints and discontinuations, Kay said, were likely the result of the nocebo effect.
But Kay, who went first in the debate, made a tactical mistake in leaving his discussion of biosimilars' presumed lower cost to his later rebuttal opportunity. When Fleischmann took the podium, he immediately shifted the focus to that issue, devoting the bulk of his remarks to a dissection of the U.S. system of drug pricing and payment.
But What About Cost?
This may have come as a surprise to some in the audience -- Fleischmann is a prominent trialist for rheumatology drugs whose conference presentations, and questions of other researchers after their presentations, normally deal with the finer points of clinical data. In this case, though, after conceding most of Kay's detailing of drug similarity, he delivered a 20-minute healthcare economics lecture.
The central question about biosimilars, he said, is this: "Do biosimilars reduce costs to the patient and to society?" He went on to argue persuasively that, in the U.S. at this point in time, and for the foreseeable future, they do not.
Why they don't, he contended, has to do with the pivotal roles of pharmacy benefit managers and vertical healthcare systems (hospital systems that also serve as insurers and medication providers) and the discounts and rebates they negotiate with drugmakers. In most cases, manufacturers of originator drugs have succeeded in keeping their products as preferred in insurers' formularies. Moreover, any savings from prescriptions of biosimilars mostly accrue to these intermediaries between drugmakers and patients -- not to the patients or to government payers. (Fleischmann didn't address whether Medicare, the VA, or other government payers might have more incentive to prioritize biosimilars, and Kay didn't call him on it.)
Fleischmann also noted the pay-for-delay deals and the "patent walls" erected by makers of originator drugs that effectively keep biosimilars off the market. The only approved biosimilar for adalimumab, Amjevita, won't be available to U.S. patients until 2023, thanks to a recent deal between its maker and AbbVie, owner of Humira. That deal came about to settle patent litigation that could have kept the biosimilar off the market for even longer.
He then addressed the situation for rheumatologists on the ground. Fleischmann called the operations director of an infusion center affiliated with his ground and asked about use of the infliximab biosimilar.
"We have tried several times with multiple insurance plans," he said the official told him. "Unfortunately, the insurance plans have requested that the official appeal, and we have not been approved even once" to use a biosimilar.
"From a patient cost perspective, the [biosimilar] costs roughly the same," Fleischmann said he was told. "There is not a savings to the patient."
Fleischmann also cited surveys of rheumatologists and recent media articles indicating that insurers are, by and large, not supporting biosimilars or the physicians who try to prescribe them.
He did concede that elsewhere in the world -- particularly Norway, where the government has made promotion of biosimilars a national policy -- that cost savings can be achieved. But in the U.S., he contended, the profit motive will prevent biosimilars from bringing cost savings to patients or society at large until the current structure, in which pharmacy benefit managers and vertical health systems are key players, is dramatically altered.
"When I treat a patient, I want them to be able to get the drug," Fleischmann said. "They should be able to be the one to get the benefit, not the way that coverage currently is done."
When Kay returned to the podium for his rebuttal, he did not deny Fleischmann's arguments, but argued that physicians must try to ensure that biosimilars become part of the mix of available drugs -- that only by breaking the monopoly held by originator manufacturers can drug prices come down.