Cindy is a 52-year-old female with non-Hodgkin lymphoma. She plans to undergo an autologous hematopoietic stem cell transplant (HSCT). When discussing the risks associated with HSCT, the oncologist warns Cindy that her white blood cells (WBCs) will become critically low as a result of high-dose chemotherapy. The low WBCs will place her at an increased risk for developing a possibly life-threatening infection. The oncologist will minimize Cindy’s risk of infection by giving her an injection of a granulocyte colony-stimulating factor (G-CSF); G-CSF is a glycoprotein that will stimulate WBC production and decrease the length and severity of neutropenia.
When the oncologist leaves the room, the registered nurse (RN) arrives to provide additional education on the transplant process and information on the G-CSF that will be administered. Cindy recently read an article about biosimilars in cancer. She asks the RN if the G-CSF will be a generic or trade name compound. Cindy is concerned the generic G-CSF will not be as effective as the original, or “innovator,” product in reducing her chance of a life-threatening infection, according to what she read on the Internet. The RN knows the institution prefers the generic filgrastim product to the trade name Neupogen. How should she address Cindy’s concerns about the safety and efficacy of biosimilar compounds?
Biosimilar Drug Development Is the Wave of the Future
Tremendous advances in the supportive care of cancer were seen in the 1980s and 1990s. Drugs developed prior to this period were traditionally manufactured through a well-defined pathway and chemical synthesis. In 1982, a genetically engineered form of insulin (Humulin) was approved by the FDA. In the 1990s, supportive care biopharmaceutical drugs such as erythropoietins and G-CSF compounds were developed using recombinant DNA or hybridoma technology to mimic endogenous human proteins.1 These synthetically manufactured drugs are called biosimilars.
The FDA has defined a biosimilar product as being highly similar to an already approved biological product. The similarity is notwithstanding minor differences in clinically inactive components, as well as no clinically meaningful differences in safety, purity, and potency between the biosimilar and the approved biological product.2 The biosimilar drugs are not exactly the same as the innovator (trade name) product, but they are considered biologically and clinically comparable to the innovator product. As of 2010, worldwide sales of biopharmaceuticals were in excess of $100 billion.3 Worldwide sales and use of biological agents in cancer and other areas such as rheumatology, immunology, and neurology are expected to increase dramatically and could rise by 75% by 2025.4
The high cost of drug development and innovation has led to an interest in developing drugs that are biologically similar to products already approved by the FDA. The surge in interest to develop biosimilars is expected to continue in the United States and worldwide. The interest is based on financial considerations to decrease healthcare costs and is also fueled by current legislation. The Patient Protection and Affordable Care Act was signed into law by President Barack Obama on March 23, 2010, and specifically addresses the topic of biosimilars. The Affordable Care Act created an abbreviated licensure pathway for biological products that are demonstrated to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product. As of March 2013, statutory conditions for the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) have been drafted. At present, investigational compounds can be considered biosimilar if data show that, among other things, the product is highly similar to existing compounds.2
Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem.5 In accordance with pharmacovigilance, the drug development process for new medicines and biosimilars requires an extraordinary amount of time and effort. The process of drug development does not stop after the approval of a drug. Ongoing evaluation and postmarketing data need to be collected to prove the long-term effects of these drugs to be similar and safe.6 Postmarketing pharmacovigilance will be necessary to establish the true safety and efficacy of biosimilar drugs.
Biosimilar filgrastims have been launched in the United States and across Europe with Neupogen as the reference or innovator product. Biosimilar filgrastims such as tbo-filgrastim (Teva Pharmaceuticals), approved by the FDA on August 29, 2012, are indicated for prevention and treatment of chemotherapy-induced neutropenia, mobilization of peripheral blood progenitor cells for HSCT, patients with acute myeloid leukemia, patients undergoing HSCT, and patients with severe chronic neutropenia.7 The approval was based on the results of studies presented for marketing authorization. The data indicate therapeutic equivalence and safety of filgrastim biosimilars in the prophylaxis of complications related to neutropenia caused by chemotherapy.8,9
How Would You Respond to Cindy’s Concerns?
There are many ways to respond to Cindy’s concerns. One approach would be to reinforce that the hospital’s decision to use biosimilars is based on evidence. There are sufficient data to support the role of a biosimilar form of Neupogen in the prophylaxis of complications related to neutropenia caused by chemotherapy. The RN can also provide additional education and ways Cindy can be proactive to decrease her risk of infection, such as good hand-washing techniques and avoidance of people with colds or illnesses. Cindy may have additional financial or psychosocial concerns the RN may explore regarding the transplant process to alleviate concerns as well.
The number of biosimilar drugs in oncology will continue to increase over the next few decades. Current government legislation supports the development of biosimilars as outlined in the BPCI Act. The use of biologically similar drugs in cancer can dramatically decrease costs to the patient and the healthcare system. Additional surveillance for long-term side effects should be conducted. All adverse events or unintended side effects must be reported to the FDA to ensure long-term safety and efficacy of each compound.
- Gascon P. Presently available biosimilars in hematology-oncology: G-CSF. Target Oncol. 2012;7(suppl 1):S29-S34.
- US Food and Drug Administration. Guidance for Industry: Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product. 2012. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291134.pdf. Accessed July 31, 2013.
- Walsh G. Biopharmaceutical benchmarks 2010. Nat Biotechnol. 2010;28:917-924.
- Jeske W, Walenga J, Hoppensteadt D, Fareed J. Update on the safety and bioequivalence of biosimilars – focus on enoxaparin. Drug Healthc Patient Saf. 2013;5:133-141.
- World Health Organization. Pharmacovigilance. 2013. www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/index.html. Accessed July 31, 2013.
- Vulto AG, Crow SA. Risk management of biosimilars in oncology: each medicine is a work in progress. Target Oncol. 2012;7(suppl 1):S43-S49.
- Neupogen [package insert]. Thousand Oaks, CA: Amgen Inc; 2013.
- del Giglio A, Eniu A, Ganea-Motan D, et al. XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. BMC Cancer. 2008;8:332.
- Gatzemeier U, Ciuleanu T, Dediu M, et al. XM02, the first biosimilar G-CSF, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with small cell or non-small cell lung cancer receiving platinum-based chemotherapy. J Thorac Oncol. 2009;4:736-740.