Future of Biosimilars Uncertain

The use of biosimilars has become widespread in Europe, but significant challenges remain to biosimilar uptake in the United States. Although biosimilars offer the promise of an effective biologic treatment at a fraction of the price of the reference product, the impact of these drugs on the market thus far has been limited, according to a session presented at the American College of Rheumatology Annual Meeting.

“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.”


However, speaker Jonathan Kay, MD, said that although the uptake of biosimilars has been slow in the United States, they have been very successful in Europe.

In Norway, a biosimilar for infliximab (Remicade) sells for 69% lower than the reference product. This large pricing difference resulted in a significant product shift and increased access to anti-TNF agents, according to the session.

“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.”


The European Medicines Agency approved its first infliximab biosimilar in 2013, while the United States approved its first inflammatory disease biosimilar for etanercept (Enbrel) in 2016, according to the session.

Dr Kay said that biosimilar approvals are increasing in both Europe and the United States.

With biosimilars, the drugs are expected to have the same clinical results and safety as the reference product, but variation is expected between batches of the drugs.

“We all have patients who notice differences between batches of a reference product,” Dr Kay 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.”


Numerous trials of biosimilars for rheumatic diseases suggest that there is little to no differences between biosimilars and the reference products, according to the session.

In the NOR-SWITCH clinical trial, 400 patients with ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, and spondyloarthritis were switched between infliximab and a biosimilar. The results suggest noninferiority, but were not statistically reliable, according to the session.

Dr Kay also discussed the BIO-SWITCH trial, which examined the effects of switching patients from infliximab to a biosimilar. While efficacy measures did not indicate a change, one-quarter of patients treated with the biosimilar stopped treatment due to perceived efficacy effects. The investigators reported that the reason patients stopped treatment was due to subjective health complaints explained by the nocebo effect.

BIO-SPAN also found a 2% percent difference in discontinuation between patients who switched to the biosimilar compared with those who stayed on etanercept. These findings may be the result of a nocebo effect, according to Dr Kay; however, Dr Fleischmann said these results demonstrate clinical reality.

“Trials are consistent,” Dr Fleischmann said. “Up to 20% 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.”


Beyond clinical data, the price reductions are not reaching patients, which is a large hurdle for biosimilars. Currently, 58% of insurers do not cover biosimilars for infliximab and other inflammatory disease biologics, representing a hurdle to uptake, according to the session.

“Biosimilars are all about decreasing patient cost and improving patient access,” Dr Fleischmann 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.”