Biosimilar Filgrastim Shows How Value Can Evolve Over Time, Study Says

A recent meta-analysis of reference filgrastim’s (Neupogen) role in chemotherapy since its approval in 1991 shows how the definition of value has evolved over time as biosimilars for granulocyte colony-stimulating factors (G-CSF) entered the market.

The authors searched for “filgrastim” in the Evidence Search Portal of the UK National Institute for Health and Care Excellence (NICE) and determined that early economic evaluations suggested that the reference biologic initially had a low value and high cost. However, although the researchers, writing in Future Oncology, noted that the early studies looked at elderly patients with aggressive non-Hodgkin lymphoma, as opposed to younger patients with less aggressive disease. However, this time period was also before biosimilars had started to enter the market.

The first NICE evidence with data to suggest any clinically and statistically significant survival benefit was not published until 2013, when a meta-analysis of 61 placebo-controlled, randomized trials with at least 2 years of follow-up showed absolute overall survival (OS) gains of 3.2% (95% CI, 2.1%-4.2%) from the use of filgrastim used along with cytotoxic chemotherapy. Improvements were seen across cancer types and dose and schedule categories, and there were decreased costs due to biosimilar competition.

The risk reduction (RR) with G-CSF support for all-cause mortality was 0.93 (95% CI, 0.90-0.96; P <.001). A greater RR was observed in studies with a longer follow-up (P = .02), where treatment was for curative intent (RR, 0.91; P <.001), where survival was the primary outcome (RR, 0.91; P <.001), and where dose-dense chemotherapy was used.

The authors said there are likely 2 reasons as to why filgrastim affected improved survival. The first is that G-CSF can improve control of infection by reducing the risk of febrile neutropenia, hospitalization, and death during chemotherapy. The second could be that G-CSF can also meet the need for improved cancer control by allowing more chemotherapy to be given on time and without the need for dose reductions, making it more effective.

The delay in published evidence in the period soon after filgrastim’s 1991 approval probably explains why G-CSF was not included in the World Health Organization (WHO) Model List of Essential Medicines, which only allows therapies that are the most efficacious, safe and cost-effective. In addition, inclusion on the list means that all therapies must be available to all citizens, either free or for an affordable price.

However, it was not until 2008 that European Union regulators approved the first biosimilars to filgrastim (ratiograstim and tevagrastim), with others following in 2014 and 2015.

With the approvals came new economic data showing the cost savings achieved by switching to the biosimilar from the reference G-CSF; one study from London hospitals showed annual savings of £1 million (approximately US $1.3 million).

Payers need to be cognizant of the changes that occur as the concept of value shifts over time with new competition, and the evolution of filgrastim “demonstrated the power of biosimilar medicines in transforming healthcare,” the authors wrote.

Reference

Cornes P, Krendyukov A. The evolution of value with filgrastim in oncology [published online March 5, 2019]. Future Oncol. doi: 10.2217/fon-2018-0762.