Biosimilars May Reduce Disparities in Febrile Neutropenia Treatment

Jeffrey Crawford, MD

Clinical gaps in febrile neutropenia care exist, according to Jeffrey Crawford, MD, a medical oncologist at Duke Cancer Center. However, biosimilars may play an interesting role in addressing those disparities.

In 2015, the FDA approved the first biosimilar to treat chemotherapy-induced neutropenia, filgrastim-sndz (Zarxio). This agent had similar safety and efficacy to the granulocyte colony-stimulating factor (G-CSF) reference agent, filgrastim (Neupogen). In February 2022, a second biosimilar, filgrastim-ayow (Releuko), was approved for the same indication with the same reference agent.

The FDA has also approved several drugs deemed to be similar to the reference agent pegfilgrastim (Neulasta). These series of approvals began with the approval of pegfilgrastim-bmez (Ziextenzo) in November 2019, followed by the approval of pegfilgrastim-apfg (Nyvepria) in June 2020, and pegfilgrastim-bmez (Fylnetra) in May 2022.

“We [now] have several biosimilars available in the US and around the world, [with the reference agents] filgrastim and pegfilgrastim” said Crawford, in a presentation on new and emerging agents on outcomes of febrile neutropenia during the 2022 Supportive Care in Cancer Annual Meeting.¹ “The potential impact of this is significant; [it represents] greater patient access, greater competition between the companies, and fostered innovation.”

Because biosimilars represent a more affordable option than their reference agent, a greater proportion of patients are eligible to receive these treatments, he explained. Moreover, manufacturers can take advantage of the latest technologies, which in turn, incentivizes investment in the development of new biologic products by originator companies, particularly because they receive budgetary relief.

The more companies in the business of producing biosimilars results in further cost reductions.

Notably, the concept of extrapolation is a powerful example of how biosimilars help increase accessibility, Crawford added. For example, when the FDA approved filgrastim-sndz based on data of a population of patients with breast cancer, they did not limit the approval to that indication. Based on that study population, the FDA was also able to approve filgrastim-sndz on the following indications: neutropenia with bone marrow transplant, neutropenia in the treatment of nonmyeloid malignancies, neutropenia in acute myeloid leukemia, severe chronic neutropenia, and peripheral blood progenitor cell mobilization.¹

“[A singular] study done in neutropenia and breast cancer treatment allowed the field—based on the biosimilar characteristics of the molecule—to extrapolate to all of the indications,” Crawford said. “That is a very important concept that reduces the cost of development.”

Crawford spotlighted trends in G-CSF following the introduction of biosimilars in the US between 2014 and 2019. He explained that findings from a cross-sectional study assessing insurance coverage of 119,129 patients treated with chemotherapy found that among those at high risk of febrile neutropenia, 75% to 83% of patients who were commercially insured, and 75% to 86% of patients who were insured with Medicare used G-CSFs. Investigators noted that this signified an overall increase in G-CSFs during this period.

Moreover, in the fourth quarter of 2019, filgrastim-sndz represented 55.6% of short-acting G-CSF use, pegfilgrastim using the on-body injector (Neulasta Onpro) represented 44.99% of long-acting G-CSF use, and pegfilgrastim biosimilars represented 29.8% of long-acting G-CSF use.

An economic analysis on biosimilar G-CSF adoption showed that in a future scenario where pegfilgrastim-bmez was used exclusively in place of pegfilgrastim, the savings could be reinvested to provide G-CSF prophylaxis (using pegfilgrastim-bmez) for at least 10% of patients who are at an intermediate risk of febrile neutropenia. This in turn, would reduce drug and administration costs, as well as reduce febrile neutropenia-related emergency visits and hospitalizations.

“The potential [for] savings [are] huge,” Crawford emphasized. “Biosimilars are going to have an impact on disparities, they are going to have an impact on utilization, impact on our practice, and [this will] expand from this area to all areas of therapeutic agents.”

Reference

Crawford J. New and emerging agents on outcomes of febrile neutropenia: addressing clinical gaps. Presented at: 2022 Supportive Care in Cancer Annual Meeting; June 23-June 25; Toronto, Ontario.