Oncology Biosimilars Can Expand Treatment Options for Seniors

A 2016 article in the Journal of Geriatric Oncology offers a detailed overview of biosimilar drugs, or monoclonal antibodies (mAbs), for the treatment of certain cancers, including the manufacturing, testing and approval processes, and implications for older patients.

Globally, over the last decade, targeted therapy with mAbs has shown efficacy and improved prognoses for patients with solid tumors or hematologic malignancies. Biosimilars first emerged in clinical use in Europe (2005) under the guidance and approval of the European Medicines Agency. In 2009, the World Health Organization released its own “Guidelines for the evaluation of similar biotherapeutic products.”

A pathway for licensure and clinical use in the United States was forged as part of the Patient Protection and Affordable Care Act of 2010 (ACA). The FDA issued its guidance documents on the testing and approval of mAbs in 2012 and 2015. Last year, the FDA approved the first biosimilar drug in the United States, Zarxio, which mimics the hematopoietic growth factor filgrastim.

Recently, the FDA released a dedicated resource in which all stakeholders can find up-to-date information on biosimilar drugs in development. The Purple Book, or Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations, is available online.

In all markets, biosimilar drugs are expected to offer useful alternatives to reference biologic products, also known as originators. These alternatives hold the promise of cost savings and greater access—especially for patients with limited means, such as many senior adults, the study found.

What is a Biosimilar

A biosimilar is a large molecule biologic drug designed to be highly similar to its reference biologic product. Unlike generics that can be chemically identical to their reference branded products, most mAbs are highly complex molecules created in vitro, using recombinant DNA technology. Then, it undergoes post-translational modifications (such as glycosylation) and are assembled in multi-chain, immunoglobulin structures. This different manufacturing process may lead to minor differences in the clinically inactive components of mAbs.

Originator products that already have, or potentially can, inspire the development of biosimilars include hematopoietic growth factors like erythropoietin and filgrastim, recombinant hormones such as growth hormones, and targeted mAbs, including anti-HER2 mAb trastuzumab, anti-CD20 mAb rituximab, and anti-epidermal growth factor receptor mAbs cetuximab and panitumumab.

To promote market competition and cost reduction, the ACA created new statutory provisions for biosimilars, called the Biologics Price Competition and Innovation Act (BPCI). The BPCI defines a biosimilar as “a biologic product that is highly similar to a reference biologic product, notwithstanding minor differences in inactive components,” and for which there are “no clinically meaningful differences in safety, purity, or potency.”

It is important to note the difference between biosimilars, which are strictly regulated, and “intended copies” or “non-comparable versions” of biologic drugs that are marketed in some parts of Central America, South America, and Asia.

Current Biosimilar Requirements

Regulations require a stepwise process of pre-clinical and clinical evaluations to determine biosimilarity.

Pre-clinical studies evaluate structural and functional properties (e.g. peptide mapping, in vitro cytotoxicity assays). In vivo animal and human studies evaluate pharmacokinetic (PK) characteristics, safety, immunogenicity, and pharmacodynamic (PD) effects.

PK and PD analyses may be used to determine biosimilarity and in vivo effects on biomarkers or target cells. PD studies should include relevance of biomarkers for the stated mechanism of action, time of onset relative to dosing, marker sensitivity to differences between the test and reference product, and correlations between changes in markers and clinical outcomes, the study noted.

Then, head-to-head clinical trials compare the biosimilar to its reference product, using populations sensitive to potential differences. Endpoints, sample size, and duration should be selected to maximize potential differences.

Rationale for Biosimilars in Oncology

Biosimilars hold the promise of cost savings, thus increasing access to therapeutic options for price-sensitive populations, such as older adults with cancer. It also acts as a hedge against other drug shortages, which have been known to negatively impact populations with cancer and may be expected to occur over the next 3-4 years due to loss of patent protection and market exclusivity for some mAbs, according to the study.

Implications of Biosimilars for Older Adults

An alternative to filgrastim is already on the market, and many other biosimilar mAbs for cancer therapy are currently in development, including alternatives to trastuzumab, rituximab, and cetuximab. The researchers added that when biosimilars enter clinical use, surveillance via pharmacovigilance programs and the reporting of adverse reactions will be especially important for older patients because comorbid conditions and reduced organ reserves can affect their drug tolerance.

The study concluded that for senior patients with cancer, lower cost biosimilars can expand treatment options and help prevent financial toxicity, thus preventing potential negative outcomes in standard of living, quality of life, treatment selection, adherence, and efficacy.