COVID19 presents challenges for healthcare systems in the United States as the number of infections continues to rise. Recently, a study published in Health Affairs found that the potential direct medical cost of treating 80% of the population with COVID-19 requiring treatment in the US could be as high as $654 billion. [1] As the US faces unprecedented challenges from both health and economic perspectives, it is time to think about fundamental ways to maintain the long-term sustainability of our healthcare system. With that in mind, we should all consider the broader adoption of biosimilars as one potential approach.

Biosimilars are biologic products that are ‘highly similar’ to the reference products (originator) in terms of safety, purity, and potency.[2] Biosimilars have the same standard of quality, yet they are more cost-effective.

In the United States, the first biosimilar was approved in 2015. [3] Since then, 26 biosimilars have been approved, [3] with 16 biosimilar products available in the market as of May 2020. [4] Sometimes, multiple biosimilars are launched simultaneously or consecutively for the same reference product. For example, there are five biosimilars available in the US that reference trastuzumab (Herceptin®; Genentech/Roche), a biologic treatment for HER2-positive breast cancer and gastric cancer. While biosimilars are proven to be comparable to and have no clinically meaningful difference from the reference product, they can be differentiated by providing improved devices and storage conditions. [5][6][7]

Biosimilars contributing to scientific advancements
One interesting aspect of biosimilars, not widely recognized by the pharmaceutical industry, is that they have contributed to the science of biologic characterization through the use of state-of-the-art assays, resulting in new insights. The work of companies developing biosimilars results in a greater understanding of the physicochemical and biologic quality attributes for both the originator reference product and the biosimilar.

In order to develop a biosimilar, companies perform extensive characterization of the reference product using a large number of highly sensitive, specific analytic tests and assays. These are used to define a set of Critical Quality Attributes (CQA) to reference when producing the biosimilar product that is highly similar to the reference product with respect to physicochemical properties, biologic and functional activity.[8] The biosimilar is often produced to a narrower specification to ensure the highest levels of quality and consistency.

Trastuzumab-dttb (Ontruzant®) is a U.S. Food and Drug Administration (FDA-) approved biosimilar of trastuzumab (reference product, Herceptin®, Genentech/Roche). Samsung Bioepsis submitted a biologics license application for approval of the drug, originally known as SB3, via the 351(k) biosimilar pathway in December 2017. The FDA approved the drug on January 21, 2019. The drug was commercially launched in the United States in April 2020 when Samsung Bioepsis and the company’s U.S. partner, Merck, made the drug available for distribution. The European Medicines Agency (EMA) approved Ontruzant, which is available in a number of European countries, for use in the EU in November 2017.

One example is with trastuzumab-dttb, a Herceptin®, biosimilar, approved by the U.S. Food and Drug Administration (FDA) in January 2019. [9] During the development of trastuzumab-dttb, the company observed a downward drift in antibody-dependent cellular cytotoxicity (ADCC) level in some of the lots of the reference trastuzumab used in the Phase 3 study comparing trastuzumab-dttb and reference trastuzumab.

Antibody-dependent cellular cytotoxicity (ADCC) is central to the mechanism of action for trastuzumab and was used as an important CQA in the development of trastuzumab-dttb.[10] In the long-term extension study involving a subset of patients from the Phase 3 study, the company observed no difference in either event-free survival (EFS) or overall survival (OS) between the trastuzumab-dttb and reference trastuzumab treated patients. However, additional subset analysis comparing the downward drifted ADCC lots versus the non-drifted ADCC lots of reference trastuzumab found that the both EFS and OS was lower in the downward drifted lots. This suggests a potential link between a biological activity CQA and patient outcomes.[11]

Biosimilars potential impact on the US healthcare system
According to an analysis conducted by the Pacific Research Institute, if biosimilars attain 75% market share, federal savings could be up to $7.0 billion annually; state Medicaid programs could save U.S. $ 1.2 billion annually, and commercial payers could save U.S. $3.3 billion annually. This study suggests that biosimilars may have an important role in realizing healthcare savings resulting in broader access to novel treatments and a more sustainable healthcare system. However, this is only possible if there is a more robust system to incentivize the uptake of biosimilar utilization, and continued efforts to improve physicians’ and patients’ perceptions of biosimilars through education.

Patients, regardless of COVID19, require regular treatment and care, and their lives should not be compromised due to cost, availability, or even supply issues with medicines. It’s time to reassess the value of biosimilars and think about practical solutions to bring more access to these cost-effective medicines.

References
[1] The Potential Health Care Costs And Resource Use Associated With COVID-19 In The United States. Online. Last accessed on May 29, 2020.
[2] U.S. Food & Drug Administration. Biosimilar and Interchangeable Products. Online. . Last accessed on May 29, 2020.
[3] U.S. Food & Drug Administration. Biosimilar Product Information. Online. Last accessed on May 29, 2020.
[4] Biosimilars Review & Report. Biosimilar Approval Status. Online. Last accessed on May 29, 2020.
[5] Fenwick S, Thakur K, Munro D. Nurse and Patient Perceptions and Preferences for Subcutaneous Autoinjectors for Inflammatory Joint or Bowel Disease: Findings from a European Survey. Rheumatol Ther. 2019;6(2):195‐206.
[6] Tischer B, Mehl A. Patients’ and nurses’ preferences for autoinjectors for rheumatoid arthritis: results of a European survey. Patient Prefer Adherence. 2018;12:1413‐1424. Published 2018 Aug 2.
[7] European public assessment report (EPAR) for IMRALDI™ (adalimumab). Online. Last accessed on May 29, 2020.
[8] U.S. Food & Drug Administration. The Draft Guidance on Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations. Online. Last accessed May 2020.
[9] U.S. Food & Drug Administration. Prescribing Information for ONTRUZANT (trastuzumab-dttb). Online. Last accessed on May 29, 2020.
[10] Kim S, Song J, Park S, et al. Drifts in ADCC-related quality attributes of Herceptin®: Impact on development of a trastuzumab biosimilar. MAbs. 2017;9(4):704‐714.
[11] X. Pivot, M. Pegram, J. Cortes, D., et al. Four-year follow-up of a Phase III study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer in neoadjuvant setting. ASCO20 Virtual Scientific Program. Abstract 578. Presented May 29, 2020.

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