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The use of biosimilars for rheumatology in the U.S. became a reality when the U.S. Food and Drug Administration (FDA) approved Inflectra (infliximab-dyyb), a biosimilar to Remicade (infliximab), in April. What this may mean is increased competition among drug companies with regard to pricing and, therefore, potentially lower costs for U.S. patients, according to Seoyoung C. Kim, MD, ScD, MSCE, Brigham and Women’s Hospital, Boston.
Dr. Kim is the lead author of “Utilization of the first biosimilar infliximab since its approval in South Korea,” which appeared in Arthritis & Rheumatology in May 2016. The study demonstrated that the introduction of biosimilar infliximab in South Korea led to a significant increase in prescriptions for the new drug, as well as decreases in the price of the brand-name reference drug.1
Aside from pricing considerations, inherent concerns exist with introducing a new class of drug to market, not the least of which is clinical efficacy and safety. The FDA’s potential fast-track approval process means that practicing rheumatologists will soon have another drug in their arsenal against rheumatic disease, and likely many more to follow.
Background
The FDA defines a biosimilar as “a biological product that is approved based on a showing that it is highly similar to an FDA-approved biological product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product.”2
Congress passed the Biologics Price Competition and Innovation Act, part of the Affordable Care Act, in 2009 in an attempt to slow upward trends in the price of biologic medications and to encourage the availability of less expensive treatments. The legislation effectively created the potential for a faster approval pathway for products that are biosimilar to or interchangeable with an FDA-licensed reference product. The FDA also published The Purple Book, an online reference that lists biologics with reference-product exclusivity, as well as the biosimilars and interchangeables (i.e., a product that is biosimilar to an FDA-approved reference product and meets additional standards for interchangeability) for each.
The FDA requires manufacturers of biosimilars to prove the drug is as safe and effective as the reference drug for approval. To date, there are few long-term studies to support the clinical safety and efficacy of biosimilar drugs for rheumatic disease, according to Dr. Kim, but more research is being published on the subject. One study showed the safety and efficacy of CT-P13, a biosimilar to Remicade, among European patients with inflammatory bowel disease.3 Multinational studies of CT-P13 showed comparable efficacy and safety over 54 weeks among patients with active rheumatoid arthritis and an inadequate response to methotrexate and ankylosing spondylitis.4,5
With regard to naming, it’s important that biosimilar drugs be clearly differentiated from their reference (or originator) drugs and from each other. To this end, the FDA published draft guidance for industry, Nonproprietary Naming of Biologic Products, in August 2015. The intent is to “clearly identify biological products to improve pharmacovigilance and, for the purposes of safe use, to clearly differentiate among biological products that have not been determined to be interchangeable.”
In practice, this means the FDA will designate biosimilars with a nonproprietary name plus a four-letter suffix. With the example of the recently approved biosimilar infliximab, the designated name is infliximab-dyyb (brand name Inflectra, reference drug Remicade).
This naming convention is a good idea, according to Dr. Kim, because it will help with accuracy in medical documentation and safety tracking. The ACR also supports the FDA’s draft guidance to make labeling and naming as transparent and specific as possible.6 “This will help ensure correct prescribing and dispensing, post-marketing surveillance, prescriber confidence and enhance market uptake,” according to an ACR news release.
On April 5, the FDA announced approval of Inflectra (infliximab-dyyb), the first biosimilar to receive approval in the U.S. for the treatment of rheumatic disease, including rheumatoid arthritis and psoriatic arthritis.7 “The ACR welcomes the introduction of biosimilars to the U.S. healthcare system and is hopeful that the decrease in cost resulting from the availability of safe and effective biosimilars in the U.S. will increase our patients’ access to life-changing therapies and improve their overall health,”8 said Joan Von Feldt, MD, MSEd, president of the ACR, in a news release.
In fact, one of the hopes for biosimilars in the U.S. market is that their availability will offer patients a lower cost alternative to brand-name drugs, or at least encourage more competitive pricing. If Dr. Kim’s research in South Korea is any indication, this may very well end up being the case.
This study & other research demonstrate that it’s not easy to predict what type of financial effect biosimilars will have on the market until they are available.
Study Overview
In their study, Dr. Kim and her team looked at usage patterns for branded and biosimilar versions of infliximab, as well as adalimumab and etanercept, before and after the biosimilar version of infliximab was introduced in South Korea in November 2012.1 They used claims data from April 2009 to March 2014 from the Korean Health Insurance Review and Assessment database, which includes the entire South Korean population (as compared with the multi-payer system in the U.S.). A segmented linear regression model was used for the analysis.
The researchers identified 20,976 users of TNF inhibitors, including 983 with a prescription claim for the biosimilar version of infliximab. The proportion of claims for the biosimilar increased to 19% through March 2014. Before November 2012, each month there were 33 more infliximab claims, 44 more etanercept claims and 50 more adalimumab claims. After the biosimilar was introduced, there were significant changes in the slopes for trends in usage and additional increases of nine more claims per month for the branded and biosimilar versions of infliximab. Comparatively, there were decreases of 52 claims per month for etanercept and 21 claims per month for adalimumab.
During the first 15 months since the biosimilar was introduced in South Korea, one-fifth of all infliximab claims were for that version as opposed to the branded version. The authors concluded that introducing the biosimilar infliximab may affect the use of other TNF inhibitors, and the magnitude of change will likely differ between what was seen in South Korea and what is experienced in other countries.
Implications
“Our study shows the utilization patterns of this biosimilar drug [infliximab] compared to the branded infliximab and a few other TNF inhibitors used for the same indications,” Dr. Kim explains. “It illustrates how the biosimilar infliximab has been playing a role in the market for patients. … In [South Korea], we observed that the uptake of the biosimilar is about 20% after 15 months of being available in the market.”
Because of the potential cost savings for patients, the uptake seen in the study was somewhat slower than expected, Dr. Kim says. The explanation, she says, is likely that the cost difference between the branded and biosimilar versions of infliximab was quite small for the majority of the study period. Initially, the biosimilar was priced about 30% less than the branded medication, but after about a month, the price of the branded version decreased. Dr. Kim hypothesizes that if there had been a bigger pricing difference, the per-person adoption may have been higher.
This study and other research demonstrate that it’s not easy to predict what type of financial effect biosimilars will have on the market until they are available. The expectation is that with increased competition, prices will drop. According to a 2014 study by the RAND Corp., cost savings in Europe may exceed $44 billion in the next 10 years, and discounts for biosimilars could be more than 35% compared with the brand-name drugs.
“If we could see that in the U.S., where we spend so much money on all these biologics, if the biosimilar could lower competitors’ prices, that would be a good thing, even if it’s only to a 30% discount,” Dr. Kim says.
Another potential reason for the lower-than-expected uptake level is that “Inflectra is basically the biosimilar of infliximab. It’s not the most common or popular TNF inhibitor, probably because it’s one of the oldest TNF inhibitors, and it requires an infusion,” Dr. Kim explains. “The initial impact of this biosimilar infliximab on the overall market may not be that big because we don’t prescribe even the branded infliximab that much. I think this is just a first step.”
In preparation for the availability of biosimilars, it’s important to explain the distinction to patients. Dr. Kim says.,“I think these concepts or the term biosimilar’need to be recognized. They are similar to the branded drug, but not necessarily the same thing.”
She adds, “The other lesson there—and that we could potentially expect in the U.S.—is potentially to have some impact on the use of other biologic drugs, and maybe there’s an indirect effect on the overall use of biologic drugs in the U.S. It may not be true at the end, but that’s what I’m thinking.”
Yet another factor that may have affected Dr. Kim’s study is that “physicians are not likely to switch [a patient] from the branded to a biosimilar drug if the patient is doing well on the branded.” So, she adds, “it is likely that you will see the use of the biosimilar in patients who are newly starting infliximab, but the proportion of these people may be quite small.”
The introduction of additional biosimilars to market, and even multiple versions of biosimilar infliximab, for example, will inherently make things more complicated. For one thing, “safety or effectiveness related to two-way switching is unknown,” Dr. Kim says. Further, it would be ideal if biosimilar drugs [even for the same reference drug] are recorded in medical records and by third-party payers (e.g., Healthcare Common Procedure Coding System “J” codes) specific to each version of the drugs, but that will become increasingly complicated as more alternatives are introduced to a single reference drug. And then, “later on, we also need to worry about switching from branded to biosimilar #1 or to biosimilar #2, or between #1 and #2, so it will get more and more complicated in potentially unexpected ways,” Dr. Kim says.
“A lot of things need to be answered in the future, but those can only be answered with time and more data.”
Kimberly J. Retzlaff is a freelance medical journalist based in Denver.
References
- Kim SC, Choi NK, Lee J, et al. Brief report: Utilization of the first biosimilar infliximab since its approval in South Korea. Arthritis Rheumatol. 2016;68(5):1076–1079.
- Information on biosimilars. U.S. Food and Drug Administration. 2016 May 10. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars.
- Smits LJ, Derikx LA, de Jong DJ, et al. Clinical outcomes following a switch from Remicade to the biosimilar CT-P13 in inflammatory bowel disease patients: A prospective observational cohort study. J Crohns Colitis. 2016 Apr 19. pii: jjw087. [Epub ahead of print].
- 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 Apr 2;18(1):82.
- 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.
- Rheumatology community responds to FDA guidance on biosimilars labeling [news release]. American College of Rheumatology. 2016 Apr 1. http://www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/735/Rheumatology-Community-Responds-to-FDA-Draft-Guidance-on-Biosimilars-Labeling.
- FDA approves Inflectra, a biosimilar to Remicade [news release]. U.S. Food and Drug Administration. 2016 Apr 5. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm494227.htm.
- Rheumatology community responds to FDA approval of Inflectra (infliximab-dyyb), a biosimilar to Remicade [news release]. American College of Rheumatology. 2016 Apr 6. http://www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/737/Rheumatology-Community-Responds-to-FDA-Approval-of-Inflectra-infliximab-dyyb-a-Biosimilar-to-Remicade.
Editor’s note: The ACR strongly believes that safe, effective treatments should be available to patients at the lowest possible cost. Decisions regarding the approval and use of biosimilars must be driven by sound science. Read the ACR’s position statement on biosimilars at http://www. rheumatology.org/Portals/0/ Files/Biosimilars-Position- Statement.pdf.
