PracticalDermatology

Biosimilars are making inroads into the treatment of psoriasis, but their US availability has been limited by patent protections. In 2023, if patent issues are resolved, the landscape of psoriasis treatment will expand.

Biosimilars are modeled after a biologic reference product that has been approved by the FDA. FDA standards apply to the approval of biosimilars to ensure that they are as safe and effective as the products on which they are based (see Examples of Biosimilars).

IMPACT OF BIOSIMILARS MAY BE LIMITED

Ideally, the availability of biosimilars for psoriasis will help bring down costs, but Guy Webster, MD, a dermatologist in private practice in Hockessin, Delaware, is not optimistic.

“A key assumption of the Hatch-Waxman Act is that competition will drive down prices, but this requires more than one generic company to enter the market and that there is no collusion,” Dr. Webster told Practical Dermatology® magazine. “Given the complexity of making biosimilars, this may be unrealistic. Add in pharmacy benefit managers and deals that insurance companies make, and the effects remain unclear.”

The key point for clinicians to know about biosimilars is that research supports their equivalent effectiveness, Dr. Webster said. Although most patients with psoriasis would not have contraindications for biosimilars, if the price is not genuinely lower, “I don’t see a reason to switch,” he said. The price should come down, but for now, no one knows, he emphasized.

According to Dr. Webster, the main barriers to the use of biosimilars are cost and acceptance by clinicians and patients. Additional research is necessary to develop more drugs beyond tumor necrosis factor (TNF) inhibitors as patents expire, he said.

DATA SUPPORT SUCCESSFUL SUBSTITUTIONS

A recent review article published in the Journal of Dermatological Treatment supports the safety and effectiveness of switching many patients with psoriasis to a biosimilar TNF inhibitor product.¹ Switching from a TNF inhibitor can refer to changing from one biologic to another, from a reference biologic to a biosimilar, or between biosimilars of the same reference product, the review’s authors wrote. Many phase 3 randomized controlled trials have assessed the outcomes of switching, but a big picture review of real-world outcomes is needed, they stated.

The review¹ included five studies of effectiveness and safety after switching patients with psoriasis from adalimumab to a biosimilar, six studies on clinical outcomes after switching from etanercept to a biosimilar or between etanercept biosimilars, and seven studies of clinical outcomes after switching from infliximab to a biosimilar or between infliximab biosimilars. Overall, the real-world evidence of safety and effectiveness was consistent with that seen in controlled trials.

“Biosimilar versions of some very effective, even revolutionary, biologic treatments used in dermatology will soon be available in the United States,” one of the review’s authors, Steven R. Feldman, MD, PhD, told Practical Dermatology® magazine. Dr. Feldman is a professor of dermatology, pathology, and social sciences and health policy at Wake Forest University School of Medicine.

“Doctors know that biologics are complex medications that no one can duplicate, which raises concerns that the biosimilars will not be identical to the innovator products,” he said. Because these medicines are so complicated, however, even the innovator reference product varies from batch to batch, he emphasized. “Our review was needed to help health care professionals understand how similar biosimilars are to the reference products that they are used to prescribing,” Dr. Feldman said.

He was not surprised by the data in the review. “Biosimilars undergo rigorous testing to show that they will act the same as the reference product does,” he said. “They have to have an identical amino acid sequence.” Biosimilars must also bind their target in the same way and demonstrate similar pharmacokinetics to the reference product, Dr. Feldman added. “Unless there’s some kind of magic going on, they should perform similarly to the innovator product,” he noted.

COST AND COMFORT LEVELS MAY LIMIT CLINICAL IMPACT

As for the clinical implications, “my enthusiasm is somewhat muted,” Dr. Feldman remarked.

“I don’t think the biosimilars are going to allow me to help patients that I can’t already help with the available agents,” he explained. “Biosimilars aren’t new drugs that can clear up a patient that didn’t respond to the innovator; they are more like another batch of the innovator.”

With regard to cost savings, Dr. Feldman said, “I don’t think the price of biosimilars is going to be so low that insurers will remove the current limitations on use of biologics. Moreover, because of strong support programs that innovator companies have offered, my patients generally have access to the drugs they need now. I’m concerned that, when biosimilars reach the market, they may not come with the same support that innovative products offer.”

In Dr. Feldman’s view, switching patients with psoriasis to a biosimiar is no different than switching among the different batches of reference biologics. “Some patients do lose efficacy to biologics over time; if that happens at the time of the switch, they’ll blame the biosimilar, even though they likely would have lost efficacy to the innovator at that time had they stayed on the innovator drug,” he noted.

The studies in the review were limited by several factors, including sample size, follow-up duration, and single-arm designs. Moreover, the investigators acknowledged that they did not examine the immunogenicity in switching from a reference product to a biosimilar. Although such a switch could promote the formation of antidrug antibodies, the same risk is present when switching from one reference product to another, they wrote. In addition, the variations in patient adherence and response to biological drugs may alter outcomes more than any minor differences between a biosimilar and any given batch of reference product, they wrote.¹

“The biggest consideration may be the hand-holding we will have to do for patients who believe there is a major difference between biosimilars and the medication they had been taking,” Dr. Feldman told Practical Dermatology® magazine. “We’ll also have to consider what insurers do, what policies they will put into place, and what carrots and sticks they may deploy to incentivize patients to make cost-wise choices of health care resources.”

Looking ahead, Dr. Feldman noted, “Numerous biosimilars are in development and should reach the market soon, and there will be additional research on whether these treatments are interchangeable with their innovative product counterparts. I think research will be needed on how health care professionals and our patients view biosimilars and how adherent the patients are to biosimilar treatment.” Long-term registries to track the safety and efficacy of biosimilars will also be valuable, he stated.

1. Ruda R, Kelly KA, Feldman SR. Real-world outcomes following switching from anti-TNF reference products to biosimilars for the treatment of psoriasis. J Dermatolog Treat. 2023;34(1):2140569. doi:10.1080/09546634.2022.2140569

Dr. Feldman reported consulting, research, and/or speaking support from AbbVie, Accordant, Almirall, Alovtech, Amgen, Arcutis Biotherapeutics, Arena, Argenx, Biocon, Bristol Myers Squibb, Boehringer Ingelheim, Caremark, Celgene, Dermavant Sciences, Eli Lilly, Eurofins, Forte, Galderma, GSK/Stiefel, Helsinn, Informa, Janssen, Leo Pharma, Menlo, Merck & Co, Micreos, Mylan, the National Biological Corporation, Novan, Novartis, Ono, Ortho Dermatology, Pfizer, Qurient, Regeneron, Samsung, Sanofi, Sun Pharma, Teladoc, UCB, UpToDate and the National Psoriasis Foundation, and vTv Therapeutics. He is also the founder and part owner of Causa Research and holds stock in Sensal Health.

Dr. Webster reported no relevant financial interest.