By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved infliximab-dyyb, a biosimilar to the reference drug infliximab (Remicade). The approval represents the first biosimilar monoclonal antibody approved in the United States. Infliximab is a chimeric, monoclonal antibody directed to anti-tumor necrosis factor (TNF). Infliximab-dyyb is marketed as Inflectra. The FDA announced that biological products licensed under the Public Health Services Act must bear a nonproprietary name that includes an FDA-designated four-digit suffix in lowercase letters (in this case “dyyb”) to distinguish products that have not been determined to be interchangeable and help with pharmacovigilance.1 The biosimilar is approved in Europe where it is marketed as Remsima.
INDICATIONS
Infliximab-dyyb is indicated for the treatment of Crohn’s disease (adults and pediatric), ulcerative colitis, rheumatoid arthritis (RA) with methotrexate, ankylosing spondylitis (AS), psoriatic arthritis, and plaque psoriasis.2
DOSAGE
The dosage is the same for infliximab (Remicade). Infliximab-dyyb is available as 100 mg lyophilized powder for IV infusion.
POTENTIAL ADVANTAGES
Infliximab-dyyb offers another, possibly less expensive, option for treatment of a number of autoimmune conditions.
POTENTIAL DISADVANTAGES
Infliximab-dyyb is currently not approved as interchangeable to infliximab.
COMMENTS
Biosimilars are biological products that are highly similar to the reference product notwithstanding minor differences in clinically inactive components. There are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.3 The FDA has determined that infliximab-dyyb meets the criteria of biosimilarity based on structural and functional characteristics, animal and human data, clinical effectiveness, safety, and immunogenicity.4 Two clinical trials have been published.5,6 Both were 54-week, randomized, parallel-group studies comparing infliximab-dyyb to infliximab in terms of efficacy, safety, pharmacokinetics, and immunogenicity. One was in patients presenting with RA not adequately controlled on methotrexate (n = 606) and the other in patients presenting with AS (n = 250). In RA, the primary efficacy endpoint was a 20% improvement in the American College of Rheumatology criteria (ACR20). Response rates were similar (74.7% for infliximab-dyyb vs. 71.3% for infliximab). Other efficacy endpoints (disease activity scores) were similar, as well as immunogenicity (antidrug antibodies) and frequencies of treatment-related adverse events. For AS, the efficacy endpoint was 20 and 40% improvement in Ankylosing Spondylitis Disease Activity Score (ASAS20/ASAS40). Response rates, safety, pharmacokinetics, and immunogenicity were similar between the biosimilar and infliximab. There is a study underway assessing the safety and efficacy of switching from infliximab to infliximab-dyyb in RA, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn’s disease, and chronic plaque psoriasis.7 Final data collection is expected to be completed in July 2016.
CLINICAL IMPLICATIONS
Infliximab-dyyb is the first approved biosimilar monoclonal antibody. It is approved for all the indications as infliximab (Remicade), with the exception of pediatric ulcerative colitis. It is currently not designated as interchangeable, which means it cannot be substituted for the reference product without provider approval. Cost was not available at the time of this review. Hospira/Pfizer may still face patent challenges from Johnson & Johnson regarding a patent that expires in September 2018, even though the U.S. Patent and Trademark Office has previously rejected the challenge by Johnson & Johnson.8
REFERENCES
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Nonproprietary Naming of Biological Products Guidance for Industry. Available at: http://1.usa.gov/1igAcNQ. Accessed April 18, 2016.
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Inflectra Prescribing Information. Hospira. April 2016.
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Biosimilars: Questions and answers regarding implementation of the Biologics Price Competition and Innovation Act of 2009. Available at: http://1.usa.gov/1JT8WdH. Accessed April 18, 2016.
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FDA approves Inflectra, a biosimilar to Remicade. Available at: http://1.usa.gov/1RWO6BF. Accessed April 18, 2016.
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Yoo DH, Racewicz A, Brzezicki J, et al. A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study. Arthritis Res Ther 2016 Apr2:82.soi:10.1186/s13075-016-0981-6.
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Park W, Yoo DH, Jaworski J, et al. Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study. Arthritis Res Ther 2016 Jan 20;18:25.doi:10.1186/s13075-016-0930-4.
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The NOR-SWITCH Study. Available at: http://1.usa.gov/1SrSkCE. Accessed April 18, 2016.
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Remicade’s U.S. patent rejection could open up early rivalry with Celltrion biosim. Available at: http://bit.ly/1YTrZOq. Accessed April 23, 2016.
