Editorials
Digestive system diseases Pharmacology
Volume 214 - Issue 3

Biosimilars: is interchangeability the proof of the pudding?

Authors:  Gregory T Moore and Charlotte Keung

Med J Aust 2021; 214 (3): 124-125. || doi: 10.5694/mja2.50912
Published online: 15 February 2021

While apparently non-inferior to originator biologics, other factors need to be considered before switching

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While apparently non‐inferior to originator biologics, other factors need to be considered before switching

Biologic drugs are large monoclonal antibodies or genetically engineered proteins produced by live organisms. With highly specific targets, they have revolutionised the treatment of inflammatory, endocrine, and malignant conditions. However, these drugs are expensive, partly because of the complex and costly manufacturing processes required, partly because long periods of therapy are often needed.

As drug patents for originator biologic drugs expire, biosimilars have been introduced to the market, reducing their price as the result of competition. The biosimilars for chronic inflammatory conditions currently subsidised by the Pharmaceutical Benefits Scheme (PBS) include the anti‐tumour necrosis factor (anti‐TNF) drugs infliximab, etanercept, and adalimumab.1

As the manufacturing process involves live organisms, biosimilars, unlike generic drugs, are not exact copies of the originator product, but Therapeutic Goods Administration (TGA) regulatory guidelines stipulate that biosimilars must be comparable in their physiochemical, biological, and immunological properties, and that they exhibit equivalent efficacy and safety.2 Further, expanding the licensing of biosimilars to the treatment of further diseases does not require disease‐specific testing but can instead be based on comparator trials for the original target condition, reducing drug development costs and the expense for patients. For example, inflammatory bowel disease (IBD) and chronic plaque psoriasis were added as indications for treatment with the infliximab biosimilar CT‐P13 on the basis of treatment studies for ankylosing spondylitis3 and rheumatoid arthritis.4

The Switching Australian patients with Moderate to severe inflammatory bowel diseasE from originator to biosimilar infliximab (SAME) study, reported in this issue of the MJA,5 is an important Australian contribution to post‐marketing information about the safety and efficacy of biosimilars for treating IBD. Haifer and colleagues found that non‐medical switching of patients with IBD from originator infliximab to CT‐P13 was not associated with differences in efficacy or side effects when compared with continued treatment with originator infliximab, consistent with the findings of previous studies. Further, switching with clinical guidance appeared acceptable to most patients; only two opted not to switch when invited to do so. Introducing biosimilar infliximab into clinical practice during 2017–2019 resulted in an overall cost reduction of $2.36 million for all treated patients, as the price of the originator was dropped to remain competitive.

The findings of Haifer and colleagues are consistent with other evidence for the efficacy and safety of infliximab biosimilars. Two randomised, double‐blinded non‐inferiority studies comparing biosimilar (CT‐P13) and originator infliximab found equivalent efficacy in different patient groups. The NOR‐SWITCH study6 included patients with several stable inflammatory conditions; while it was not powered to evaluate individual conditions, their efficacy for those with Crohn disease was similar. More recently, a 26‐week extension study to NOR‐SWITCH found that the biosimilar was not inferior to originator infliximab for treating patients with IBD.7 The only randomised, double‐blinded study assessing CT‐P13 treatment of biologic‐naive patients with active Crohn disease also found it was non‐inferior to the originator over 54 weeks.8 Importantly, neither study reported any significant differences in the rates of anti‐drug antibody development. In fact, cross‐immunogenicity between anti‐drug antibodies to originator and biosimilar drugs have been found for both infliximab and adalimumab, with similar antibody titres.9,10 The open label SECURE study also found comparable drug levels of infliximab in both biosimilar and originator groups after switching to CT‐P13 at 16 weeks.11

In Australia, infliximab biosimilars have been relatively easily integrated into routine clinical care in IBD services, both for biologic initiation and non‐medical switching. This was facilitated by the highly controlled treatment environment, jointly coordinated by specialist clinicians and hospital pharmacists, with patient education and consent. Further, the nature of intravenous infusions of agents such as infliximab allows local control and oversight. Pharmaceutical companies have also continued to support patients who require dose acceleration beyond quantities subsidised by the PBS.

As several adalimumab biosimilars, including self‐administered biosimilars, have been or will soon be approved for clinical use, oversight over switching biologics will probably be reduced. The vast majority of self‐administered biologic drugs are dispensed by community pharmacies, and the “a” flagging of PBS‐listed drugs allows switching at the point of dispensing with the patient’s consent but without clinician involvement, unless “brand substitution not permitted” has been specified by the prescriber.12

The importance of clinician support for successful non‐medical switching should not be underestimated, both with respect to patient acceptance of biosimilars and the nocebo effect, a key driver of biosimilar discontinuation in observational and open label studies.13 While evidence for the safety for multiple switches has been reported,14 long term effects are unknown. Further, without a robust pharmacovigilance reporting system, adverse drug events associated with successive switches may be missed. Additionally, differences in injection devices and the ongoing provision of pharmaceutical company‐funded patient support programs and compassionate drug supply need to be taken into account when considering switching.

Looking toward the future of complex chronic disease management, the introduction of novel small molecule therapies, such as Janus kinase (JAK) inhibitors, will change practice once again by reducing production and cold chain costs, and because they are less immunogenic than biologics.15 But for now, the biosimilar interchangeability “pudding” seems safe and economical.

 

Authors

  • Gregory T Moore1,2
  • Charlotte Keung1
  • 1. Monash Health, Melbourne, VIC
  • 2. Monash University, Melbourne, VIC

Correspondence: gregory.moore@monash.edu

Competing interests

Gregory Moore has received payment for advisory boards from AbbVie, BMS, Chiesi, Emerge, Gilead, Hospira, Janssen, Orphan, MSD, Pfizer, Shire, Takeda; speaker’s fees from AbbVie, Ferring, Janssen, Orphan, Pfizer, Roche, Shire, and Takeda; and research and educational support from AbbVie, Janssen, Pfizer, Shire, and Takeda.

References

Linked content

  • MJA Research: Switching Australian patients with moderate to severe inflammatory bowel disease from originator to biosimilar infliximab: a multicentre, parallel cohort study

Provenance: Commissioned; externally peer reviewed.

View this article on Wiley Online Library