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A biosimilar is a biological medicine deemed highly similar to an existing, approved originator biological medicine (such as reference infliximab, reference medicine, and biological reference medicine) based on the same active ingredients.

Biosimilars are not the same as generics (i.e., copies of original synthetic chemical drugs). Unlike generics, biosimilars are as structurally complex as originator biologics. There is a certain degree of variability in the molecules of an active substance in each batch because of how they are produced in living organisms. Such variability exists both in originator biologics and biosimilars. 

A biosimilar is strictly assessed through clinical trials to prove its similarity to an existing, approved originator biological drug in terms of quality, safety, and efficacy. To get approval, it needs to show that the variability and difference between the biosimilar and the originator medicine will not affect its safety or impact. Once it is proven that there is no clinical difference between them (equivalence or bioequivalence test), the biosimilar can be used to treat the same conditions as the originator medicine at the same doses.

Since their introduction, originator biologics have contributed to improving patient outcomes. However, their high cost places a considerable burden on health-care systems and can affect patients’ access to treatment. Biosimilars, therefore, could offer considerable cost savings to health services, especially as they are often used to treat long-term conditions. They can also increase the number of patients with higher access to biological therapies.

Research has shown that between 2007 and 2020, the use of biosimilars is expected to result in overall savings of between EUR 11.8 billion and EUR 33.4 billion, with biosimilar mAbs producing the greatest savings ranging from EUR 1.8 billion to EUR 20.4 billion.

An evaluation of the budget impact of the introduction of Remsima® in the treatment of rheumatoid arthritis demonstrated that the total five-year cost-saving across the United Kingdom, Italy, Germany, and France would range from EUR 96 million to EUR 433 million. A further budget impact study has analyzed the substantial cost savings associated with the introduction of Remsima® in Crohn’s disease (CD). The model showed that the total five-year saving across the United Kingdom, Italy, and France ranged from EUR 77 million to EUR 336 million.

As the health-care costs increase along with financial burden international- and national-level policymakers and insurance companies have been actively promoting the use of biosimilars as an economical alternative to originator biologics by creating a regulatory and market environment in favor of the biosimilar developers.

For example, the Norwegian government carried out a research project to evaluate the safety and efficacy of biosimilar infliximab switching from an original medicine for the treatment of all approved indications. According to the research results that came out in late 2016, there was no significant difference between Remsima®, the biosimilar infliximab, and the originator medicine, which eventually contributed to the widespread of biosimilars. In addition, British, Denmark, and Italian governments officially recommended switching from the original medicine to Remsima® for the treatment of specific indications such as rheumatoid arthritis. In France, medical specialists have been recommended to prescribe generics and biosimilars to 70% of naïve patients since 2017 to increase the prescription rate of biosimilars by 80% for five years from 2018 to 2022.

In the United States, which is known for having the largest biological medicine market, the U.S. Food and Drug Administration (FDA) announced the Biosimilars Action Plan (BAP) in July 2018 to promote the prescription of biosimilars, with a plan to consistently establish sub-plans to increase the use of biosimilars. Furthermore, the Center for Medicare and Medicaid Service (CMS), a federal agency within the U.S. Department of Health and Human Services decided to revise the reimbursement system in disfavor of biosimilars and implement it starting from January 1, 2018. In addition, constant efforts have been made in the United States to create an environment in favor of biosimilars, including the approval of Step Therapy that encourages doctors to prescribe medicines with price competitiveness falling into the category of Medicare Part B to new patients starting from January 1, 2019.

Biosimilars must comply with quality requirements related to originator biologics while undergoing the same rigorous assessment process led by regulatory agencies in each country.

Regulatory agencies demand that a biosimilar be used to treat the same conditions as an originator medicine at the same dose after it is proven that these two are similar in terms of efficacy and safety. Originators have long been used when prescribed, and the clinical benefit has been already confirmed so that there is no need for further research on the originator itself.

Since 2006, more than 10 types of the first-generation biosimilars have been approved; however, Remsima is the world’s first biosimilar monoclonal antibody (mAb) approved by the European Medicines Agency (EMA). EMA confirmed that Remsima is similar to its originator medicine in terms of efficacy and safety and acknowledged that it is a safe and effective biological medicine by granting marketing authorization.

Once a biosimilar and an originator medicine are clinically proven to be similar in terms of quality, safety, and efficacy, the biosimilar can be used to treat the same conditions as the originator medicine at the same dose. This has become the basis for Remsima getting the approval of all eight therapeutic indications held by the originator medicine based on the clinical data about rheumatoid arthritis and ankylosing spondylitis.

A biosimilar is considered similar to a reference medicine after it is proven through clinical tests that these two are similar in terms of efficacy and safety, and there is no significant difference between the two.

Regulatory agencies, such as the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA), have different perspectives on prescribing biosimilars to those already taking reference medicines.

EMA’s current position is that those decisions on interchangeability and/or substitution rely on competent national authorities and are outside the remit of EMA/CHMP; the Member States have access to the scientific evaluation performed by the CHMP and all submitted data to substantiate their decisions.

Meanwhile, the position of the FDA is that to meet the higher standard of “interchangeability” and show that the biological product can be expected to produce the same clinical result as the reference medicine in any given patient, an applicant must provide sufficient information to demonstrate biosimilarity.

Data from extension phases of the two clinical trials (PLANETRA and PLANETAS) have been published in the Annals of the Rheumatic Diseases. The data show that it is possible to switch from the reference infliximab to Remsima® without any detrimental effects on safety or efficacy. Moreover, the studies show that CT-P13 is well tolerated and effective for up to two years for patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS).

In addition, the NOR-SWITCH Study in Norway assessed the safety and efficacy of switching from the reference infliximab to Remsima® for patients with rheumatoid arthritis, spondylarthritis, psoriatic arthritis, ulcerative colitis, Crohn's disease, and chronic plaque psoriasis. The study was undertaken in 18 hospitals in Norway. According to its clinical results published in 2016, it was proven that switching from RMP to Remsima is non-inferior to continuing with the RMP treatment.

According to Frost & Sullivan, original biologics are expected to dominate the market along the existing sales pipelines for a certain period. Nevertheless, it is predicted that the market share of biosimilars in the global biological medicine market will dramatically increase from 1.9% in 2016 to 14.2% in 2026. Such change will be brought about by the low costs of biosimilars compared to their originator medicines with the same efficacy, the patent expiration of original biologics, the regulatory environment in favor of biosimilars, and the health-care budget pressure.

From 2016 to 2026, the annual growth rate of biosimilars is expected to reach 34.0%, which is a lot higher than that of originator biologics, that is 8.4%.