Data Support Safety, Efficacy of Biosimilar-to-Biosimilar Switching

A growing body of evidence supports the safety and efficacy of biosimilar-to-biosimilar switching.

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With a growing pool of data, the evidence supports the practice of biosimilar-to-biosimilar switching with no safety concerns and similar efficacy, according to a piece from Hillel P. Cohen, PhD, and Wolfram Bodenmueller, PhD, of Sandoz. The article, which reviewed the findings of biosimilar-to-biosimilar switching studies, was published in BioDrugs.¹

In the United States, the FDA has approved 48 biosimilar products² with the most recent being the second tocilizumab biosimilar (tocilizumab-aazg; Tyenne), which was approved March 7, 2024.³ For many molecules there are several biosimilars approved. Adalimumab (Humira) leads the way with 10 approved biosimilars, but pegfilgrastim (Neulasta) has 6, and trastuzumab (Herceptin) and bevacizumab (Avastin) each have 5.

“As a result, patients, healthcare professionals, and formularies are increasingly exposed to the practice of switching between different biosimilars of the same biological reference product in real-world settings,” Cohen and Bodenmueller explained.

In an update to an earlier systematic review on the same subject,⁴ the authors reviewed biosimilar-to-biosimilar switching studies published between January 1, 2022, and December 31, 2023.

As of December 31, 2023, there have been 31 observational studies with a total of 6081 patients across all studies contributing to the evidence base supporting biosimilar-to-biosimilar switching. The majority (67.7%) of studies and abstracts analyzed evaluated infliximab (Remicade). There were 7 (22.5%) studies and abstracts for adalimumab, 2 (6.3%) studies in etanercept (Enbrel), and 1 study for rituximab (Rituxan).

The indications evaluated across the studies and abstracts included rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, ankylosing spondylitis, Crohn disease, and ulcerative colitis. A total of 23 of the studies were initially included in the 2022 review; however, 5 had been congress abstracts and have since been published as full, peer-reviewed papers.

There were 3 new observation studies and 1 new single-center retrospective study of infliximab that hadn’t been included in the 2022 review. One study compared patients who switched to a biosimilar from the reference compared with patients who switched from one biosimilar to another, while the other studies analyzed patients who switched from one biosimilar to another. The studies all showed that switching between biosimilars was well tolerated, did not lead to treatment discontinuation, and was effective with no loss of clinical, functional, or inflammatory remission.

There were 4 new adalimumab studies. One studied patients who switched to a biosimilar either from another or from the reference; one studied patients who switched from the reference to a biosimilar and then switched again to another biosimilar a year later; and another 2 evaluated patients who switched from one biosimilar to another. All of these showed clinical remission rates were unchanged, drug sustainability was high, and no difference in efficacy.

The observational nature of the studies included was one limitation of this meta-analysis. Another was that biosimilar-to-biosimilar switching has only been evaluated in a small number of molecules, despite many more having multiple biosimilars available. In addition, many of the individual studies had small numbers of patients enrolled.

“We believe that the available data suggest that as a scientific matter, the practice of biosimilar-to-biosimilar switching is as safe and effective as being treated solely with either a reference biologic or a single biosimilar or the switch from a reference biologic to its biosimilar,” the authors concluded. “Any suggestions to the contrary are not supported by clinical evidence or the underlying science.”

The authors are both employees of Sandoz, which manufactures and markets multiple biosimilars worldwide, including adalimumab-adaz (Hyrimoz), bevacizumab-tnjn (Avzivi), denozumab-bddz (Jubbonti and Woost), etanercept-szzs (Erelzi), natalizumab-sztn (Tyruko), pegfilgrastim-bmez (Ziextenzo), and filgrastim-sndz (Zarxio), the first FDA-approved biosimilar.

Reference

1. Cohen HP, Bodenmueller W. Additional data in expanded patient populations and new indications support the practice of biosimilar-to-biosimilar switching. BioDrugs. Published online March 23, 2024. doi:10.1007/s40259-024-00655-4

2. Biosimilar product information. FDA. Updated March 12, 2024. Accessed March 29, 2024. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information

3. Jeremias S. FDA green lights second tocilizumab biosimilar. The Center for Biosimilars^®. March 7, 2024. Accessed March 29, 2024. https://www.centerforbiosimilars.com/view/fda-green-lights-second-tocilizumab-biosimilar

4. Cohen HP, Hachaichi S, Bodenmueller W, Kvien TK, Danese S, Blauvelt A. Switching from one biosimilar to another biosimilar of the same reference biologic: a systematic review of studies. BioDrugs. 2022;36(5):625-637. doi:10.1007/s40259-022-00546-6