Molecular profiling and other advanced diagnostic techniques are changing the way many cancers are identified and treated. The past decade has seen a shift in the concept of cancer therapy. New immunotherapy medications target immune cells, thereby inducing the immune system to eradicate tumor cells.
The National Cancer Institute defines biological drugs, also referred to as biologics, as generally large, complex molecules or mixtures of molecules that are derived from living organisms, such as yeast, bacteria, or plant or animal cells.1 Because of molecular profiling, biologics can offer personalized treatment that often improves clinical outcomes, extends survival, and restores patients’ quality of life in a way that chemotherapy cannot. However, these medications can be expensive, thus creating a barrier to their access. The good news is that biosimilar medications are increasingly available to reduce this barrier.
Each biosimilar drug is highly similar to its FDA-approved reference biologic in terms of efficacy, safety, and quality without being identical to it. Although biosimilars are created slightly differently (but also from living organisms and using molecular targets), the clinical setting, treatment approach, and dose used should be identical to their reference drugs. Of course, they also must carry FDA approval.1 An advantage to using biosimilar drugs is that they are often less costly than the reference drugs, making them more accessible.2
Acceptance of biosimilars was boosted by the Biologics Price Competition and Innovation Act of 2009. Although their economic advantage got off to a slow start, predictions are now that they will reduce the cost of biologic medication by $100 billion over the next 5 years.3 Some patents for oncology biologics have expired, and biosimilars for these drugs have been approved both in the European Union (EU) and in the United States. As of May 2021, 39 biosimilars of filgrastim, bevacizumab, trastuzumab, pegfilgrastim, and rituximab have been approved in the EU, and 14 oncology biosimilars were approved by the FDA for use in the United States.4,5 Table 1 shows the oncology biosimilar drugs approved by the FDA for use in the United States.5
Table 1. Oncology Biosimilar Drugs with US FDA-Approval5
|Pegfilgrastim-jmdb (Fulphila)||Pegfilgrastim (Neulasta)||Mylan/Biocon|
|Trastuzumab-pkrb (Herzuma)||Trastuzumab (Herceptin)||Celltrion Inc.|
|Trastuzumab-anns (Kanjinti)||Trastuzumab (Herceptin)||Amgen Inc.|
|Bevacizumab-awwb (Mvasi)||Bevacizumab (Avastin)||Amgen, Inc.|
|Filgrastim-aafi (Nivestym)||Filgrastim (Neupogen)||Pfizer Inc.|
|Trastuzumab-dkst (Ogivri)||Trastuzumab (Herceptin)||Mylan|
|Trastuzumab-dttb (Ontruzant)||Trastuzumab (Herceptin)||Samsung Bioepis|
|Epoetin alfa-epbx (Retacrit)||Epoetin alfa (Epogen)||Hospira Inc.|
|Rituximab-pvvr (Ruxience)||Rituximab (Rituxan)||Pfizer Inc.|
|Trastuzumab-qyyp (Trazimera)||Trastuzumab (Herceptin)||Pfizer Ind.|
|Rituximab-abbs (Truxima)||Rituximab (Rituxan)||Celltrion Inc.|
|Pegfilgrastim-cbqv (Udenyca)||Pegfilgrastim (Neulasta)||Coherus Biosciences|
|Filgrastim-sndz (Zarxio)||Filgrastim (Neupogen)||Sandoz Inc.|
|Bevacizumab-bvzr (Zirabev)||Bevacizumab (Avastin)||Pfizer Inc.|
How Biosimilars Differ From Generics
Biosimilars are different from generic drugs. Generics have the same active ingredients as the brand name medication they copy, whereas biosimilars are made of slightly different substances.1 The manufacturing process of biosimilars also is unique. As part of the process, a company must analyze the original reference biologic along with the biosimilar they are creating to ensure the purity of the biosimilar as well as its bioactive and biochemical similarity. Each lot undergoes a strict control process to ensure consistency. Every definition of biosimilar medication states there can be no “clinically meaningful differences.”4 The manufacturer often accomplishes this by running postmanufacture clinical trials.
In contrast, manufacturers of generic drugs only need to prove that their products are bioequivalent to the brand name medication they are copying, that is their products have identical active ingredients as the original drug. For this reason, automatically substituting a generic for a brand name medication is a widely accepted practice that cannot be applied to biosimilars.
Additional differences between the 2 types of products include structure, immunogenic potential, switchability, preclinical studies, storage requirements, and time to market.
Structure Generics are simple molecules with the same amino acid sequence and well-defined structure. In comparison, biosimilars are made with complex molecules. They have slight differences in structure but the same primary amino acid sequence.
Immunogenic potential Biosimilars can be immunogenic, whereas generics have no such potential.
Switchability More studies are needed on whether biosimilars could be switched or interchanged with their reference drugs. Generics, on the other hand, can be switched with the original medication.
Preclinical studies Biosimilars require complete preclinical studies, whereas generics only require bioequivalence studies.
Storage requirements Special conditions must be maintained when storing biosimilars because of the high sensitivity of these products. However, generics are stable and easy to store.
Time to market Biosimilars can take 7 to 8 years from development through FDA approval and availability on the market. Generics complete the process receiving approval in only 2 or 3 years.5
A prescribed reference medication can be changed to a biosimilar only if the laws of the state allow, and the physician approves, making the change. Often, indications for use also are different between the biosimilar and the reference product because biosimilars may not be approved for as many indications as the reference product.
The Purple Book
The FDA created the “Purple Book: Database of Licensed Biological Products,” a reference originally available as 2 separate lists: FDA-licensed biological products regulated by the Center for Drug Evaluation and Research (CDER) and FDA-licensed biological products regulated by the Center for Biologics Evaluation and Research (CBER). The reference is no longer an actual book; it is an easily searchable online database that contains information about biological products, including biosimilar and interchangeable products, licensed and approved by the FDA under the Public Health Service (PHS) Act. 6
- National Cancer Institute. Biosimilar drug. Accessed October 20, 2021. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biosimilar-drug
- IQVIA Institute for Human Data Science. Biosimilars in the United States 2020-2024: Competition, Savings and Sustainability. IQVIA Institute; October 2020. Accessed October 10, 2021. https://www.iqvia.com/insights/the-iqvia-institute/reports/biosimilars-in-the-united-states-2020-2024
- Liu Y. Utilizing oncology biosimilars to minimize the economic burden associated with cancer treatment: managed care considerations. Am J Manag Care. 2021;27(14 Suppl). doi:10.37765/ajmc.2021.88734
- Peeters M, Planchard D, Pegram M, Gonçalves J, Bocquet F, Jang H. Biosimilars in an era of rising oncology treatment options. Future Oncol. Published June 30, 2021. doi:10.2217/fon-2021-0546
- Konstantinidou S, Papaspiliou A, Kokkotou E. Current and future roles of biosimilars in oncology practice. Oncol Lett. 2020;19(1):45-51. doi:10.3892/ol.2019.11105
- U.S. Food & Drug Administration. Purple book: lists of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations. Last updated August 3, 2020. Accessed October 20, 2021. https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/purple-book-lists-licensed-biological-products-reference-product-exclusivity-and-biosimilarity-or