Biosimilars are a great idea whose time has not come, at least not in the United States.
“The whole rationale behind biosimilars is that they would be as effective, as safe, and considerably cheaper than the reference product,” said Roy Fleischmann, MD, MACR. “For my patients in the United States, there are no savings from biosimilars. The savings, if there are any, go exclusively to pharmacy benefit managers and vertically integrated healthcare systems. There is no benefit in cost to patients and no improvement in access to biologic therapy to patients.”
Dr. Fleischmann supported the con side in GREAT DEBATE: Biosimilars…To Switch or Not to Switch? That Is the Question on Sunday afternoon. He is Clinical Professor of Medicine at the University of Texas Southwestern Medical Center and Co-Medical Director of the Metroplex Clinical Research Center.
On the pro side was Jonathan Kay, MD, Professor of Medicine and Timothy S. and Elaine L. Peterson Chair in Rheumatology at the Massachusetts Medical School. Biosimilars may be off to a slow start in the U.S., he agreed, but have provided significant cost savings in Europe.
In Norway, infliximab biosimilar was priced 69 percent below the cost for the reference product in 2015, prompting a massive product switch. Across the EU, anti-TNF agents have significantly increased access to therapy.
“A biosimilar is no more different from the reference molecule than the reference molecule is different from itself in prior versions of the same product,” Dr. Kay said. “Different batches of biosimilars and different batches of their reference products are both versions of the same reference molecule.”
Biosimilars for inflammatory diseases have been available in Europe since the European Medicines Agency (EMA) approved its first infliximab biosimilar in 2013. An etanercept biosimilar in 2016 was the first U.S. approval in inflammatory diseases. The pace of biosimilar approval is increasing, Dr. Kay said, with at least eight biosimilar approvals for inflammatory diseases by the EMA, the FDA, or both in 2017.
The goal of biosimilar manufacturers is to produce an agent that has the same clinical effect as the reference product and is at least as safe, he said. Regulators expect variation between batches just as they expect between batches of the reference product.
“We all have patients who notice differences between batches of a reference product,” he said. “Variations from batch to batch can have clinical effects that we do not recognize because we don’t keep track of batches. Once approved, a biosimilar is like any other batch of its reference product.”
Multiple trials of multiple biosimilars in rheumatoid arthritis, psoriasis, and other rheumatic diseases show little to no clinical differences between biosimilars and reference products.
The NOR-SWITCH study looked at switches between infliximab and a biosimilar in 400 Norwegian patients with ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, and spondyloarthritis.
The trial showed noninferiority for the biosimilar in the total population, Dr. Kay reported. Individual disease populations were too small to provide statistically reliable results.
Other data are more problematic. In the Netherlands, BIO-SWITCH examined the effects of switching patients from infliximab to a biosimilar. Objective measures of efficacy showed no change, but a quarter of patients who switched to the biosimilar discontinued treatment due to subjective health complaints, according to the study authors.
BIO-SPAN, also in the Netherlands, found a two percent difference in discontinuation in the etanercept biosimilar after switching compared to patients who remained on etanercept. Dr. Kay attributed the negative findings to the nocebo effect.
Dr. Fleischmann said the findings reflect clinical reality.
“Trials are consistent,” he said. “Up to 20 percent of patients had problems switching because they lost clinical effect. Switching doesn’t work for every patient. And when you look at NOR-SWITCH, the data are inconclusive for noninferiority in rheumatoid arthritis, Crohn’s, and psoriasis. We need much more data for a longer period of time to validate the safety of biosimilars.”
Dr. Fleischmann reiterated that however one interprets the trial data, list price reductions for biosimilars do not reach patients. In the U.S., 58 percent of insurers do not cover biosimilars for infliximab and other inflammatory disease reference biologicals.
“Biosimilars are all about decreasing patient cost and improving patient access,” he said. ”The cheaper drug, if it is similar, should be the first drug used, and it is not. Saving money for insurers is not a reason to switch to biosimilars.”