Updates from the annual ASH meeting, December 2018.
The launch of biosimilar rituximab is an eagerly awaited event among US healthcare stakeholders who are cognizant of the high cost of intravenous (IV) administered rituximab in treating non-Hodgkin lymphoma (NHL).1 At the same time, another innovation in rituximab delivery—a subcutaneously administered rituximab formulation—has the potential to save both cost and time.
During the 60th American Society of Hematology Annual Meeting & Exposition in San Diego, California, researchers presented findings from a time-and-cost simulation of subcutaneous rituximab (Rituxan Hycela), brand-name IV rituximab (Rituxan), and biosimilar IV rituximab from the US payer perspective.2 The simulation analysis was performed for 1 patient with NHL over the course of 6 cycles of treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) using either standard or rapid infusion times.
The investigators derived costs of the subcu- taneous and the IV reference rituximab products from first-quarter 2018 average sales prices and 2018 reimbursement rates as listed in the Current Procedural Terminology code set. Costs for the proposed biosimilar were estimated at 15% to 35% discounts to the reference IV rituximab.
The investigators found that, following the first cycle of IV reference rituximab, switching to the subcutaneous formulation saves 650, 720, and 791 minutes (for patients with small, average, and large body sizes, respectively) over the next 5 cycles compared with continuing to use an IV option.
Costs for 6 cycles of R-CHOP, assuming a switch from the IV reference rituximab to the subcutaneous presentation at cycle 2, were $54 higher than rapid infusion but $104 lower than the standard infusion of the IV reference for patients with small body size. For patients with medium body size, the cost of subcutaneous administration was $3854 and $4012 lower than the cost of rapid and standard IV administration, respectively. For patients with large body size, the subcutaneous product saved $7762 and $7920 versus the 2 IV infusion speeds.
However, compared with an IV biosimilar rituximab, the subcutaneous option was costlier. For patients with small body size, the subcutaneous formulation cost between $3647 and $8649 more versus standard infusion and between $3805 and $8807 more versus rapid infusion of the biosimilar. For patients with medium body size, these ranges were $325 to $6109 and $484 to $6267 for the 2 infusion speeds. For patients with large body size, at a biosimilar discount of 25% or greater, subcutaneous administration cost at least $286 more than a standard infusion rate, and at a discount of at least 24%, at least $116 more than the biosimilar delivered by rapid infusion.
The researchers concluded that, although subcutaneous rituximab in R-CHOP saves on both time and cost versus using the reference IV rituximab, using a biosimilar IV rituximab saves on costs versus subcutaneous administration in small- and average-sized patients at all levels of biosimilar discount, and in large patients if discounted by 25% and 24%.
In an email to The Center for Biosimilars®, the research team said that, although further investigation is warranted to better evaluate whether these time and cost savings can be achieved in clinical practice, “we believe in the value of simulation models to advance our understanding of the potential time- and cost-savings for different formulations of oncology biosimilars. Further real- world evidence is essential in helping assess how biosimilars may help enable access to medicines for patients who may not otherwise afford them.
“What we can say,” added the authors, “is that biosimilar medicines are the future of healthcare, providing vital treatments for prevalent, chronic cancer conditions. And, biosimilars deliver the same efficacy and safety that patients and physicians trust and rely upon from reference biologics.”
Although the prophylaxis of neutropenia is crucial for patients undergoing cytotoxic chemotherapy to maintain dose intensity of their anticancer regimens, using granulocyte colony-stimulating factor (G-CSF) agents does increase the cost of treatment. Long-acting G-CSF agents (such as pegfilgrastim) instead of short-acting agents (like filgrastim) has the potential to push costs even higher. For health systems like the Veterans Health Administration (VHA), where controlling costs while providing high-quality care is of heightened concern, achieving the best value for money in the prophylaxis of neutropenia can help to control the cost of cancer care.
During the 60th American Society of Hematology Annual Meeting and Exposition in San Diego, California, Kevin Knopf, MD, chairman of hematology/oncology at Highland Hospital in Oakland, California, and colleagues presented research on the most cost-effective approach to using G-CSF therapies in the VHA.1
Knopf and his team surveyed 23 VHA sites on their use of brand- name filgrastim (Neupogen); tbo-filgrastim (Granix), a follow-on filgrastim that was approved prior to the establishment of the US’ biosimilar approval pathway; biosimilar filgrastim (Zarxio); and brand-name pegfilgrastim (Neulasta). The researchers also estimated costs for the use of G-CSFs based on 340B pricing. Biosimilar pegfilgrastim was not included in this analysis.
The most cost-effective strategy, they found, was to use only tbo-filgrastim, as such an approach would result in a cost of $62,336 per 100 patient episodes. Eighteen of the 23 surveyed sites used tbo-filgrastim as their preferred treatment, making the VHA 73% efficient and highly cost-effective. Costs for G-CSF use in each of the sites ranged from a minimum of $62,336 per 100 patient episodes in 4 sites to a maximum of $201,356 per 100 patient episodes at 2 sites, delivering a mean cost of $99,080. Most sites, the researchers reported, were able to avoid the use of the long- acting and higher-cost pegfilgrastim; only 27% of patients across the surveyed hospitals had received Neulasta.
Furthermore, the adoption of biosimilar and follow-on filgrastim in the VHA has been rapid, the researchers said. None of the sites surveyed were using the brand-name filgrastim for new patients, and 6 of the 23 sites indicated that they were comfortable with switching patients who had previously received the branded filgrastim to a cost-saving option. Despite the willingness of the VHA to adopt follow-on and biosimilar filgrastim, however, simply switching patients to tbo-filgrastim from the brand-name option provided only a small cost savings—just 2.2%—under 340B pricing.
According to the authors, other approaches to reducing the cost of G-CSF therapy are likely to have a greater impact on the overall cost of care than a switch to biosimilars. Such approaches include avoiding the use of G-CSF therapies in cases in which there is no convincing evidence of their efficacy (for example, in patients who are classified as low-risk), and continuing to use short-acting agents instead of long-acting ones whenever possible.
Furthermore, Knopf said in an interview with The Center for Biosimilars®, there is some limited evidence that it may be feasible to prevent neutropenia by using 2-day or 4-day courses of filgrastim rather than 8-day courses. He cited a nonrandomized trial conducted in the 1990s that found that, in patients with early breast cancer, the frequency of G-CSF administration could be shortened to just 2 administrations, on days 8 and 12, without altering the patients’ outcomes.2
Knopf emphasized that further investigation will be necessary to demonstrate whether shorter treatment courses are indeed effective, such an approach could deliver an additional 50% to 75% cost savings.
In 2016, the Saskatchewan Cancer Agency switched from the brand-name filgrastim, Neupogen, to a biosimilar, Apotex’s Grastofil, for stem cell mobilization prior to autologous stem cell transplants (ASCTs).
In a study presented at the 60th American Society of Hematology Annual Meeting, held December 1-4, 2018, in San Diego, California, researchers sought to determine the safety and efficacy of using a biosimilar for this setting.1
In order to analyze the efficacy of the 2 products, the study’s authors reviewed patient charts and compared the efficacy of CD34+ collection in 170 patients who received the brand-name filgrastim with 47 patients who received the biosimilar between 2012 and 2018.
They found that the brand name and the biosimilar demonstrated similar efficacy for stem cell mobilization, as 92.4% of the patients treated with the brand name product had a successful harvest (defined as a collection of 2x106 or more CD34+ cells for patients planned for 1 stem cell transplant and 4x106 or more CD34+ cells for patients planned for
2 transplants), compared with 100% of the patients taking the biosimilar.
In addition, the study’s authors also looked at the efficacy of mobilization with both filgrastim products, either alone or in combination with chemotherapy, in patients requiring more than 1 apheresis day and requiring the stem cell—stimulating agent, plerixafor. Clinical efficacy was defined in this portion of the study by using time to engraftment and length of hospital stay post- ASCT as parameters.
Importantly, the 2 products did not demonstrate a statistically significant difference in plerixafor requirement when patients had a low CD34+ count. There was also no statistically significant difference between each patient group that required more than 1 day of apheresis. In total, 59.4% of patients mobilized with the branded product required
more than 1 apheresis day compared with 76.9% of patients mobilized with the biosimilar (P = .11).
Similarly, the researchers found that 42.5% of patients in the reference product group received chemotherapy, compared with 38.1% in the biosimilar group, a difference that was not statistically significant (P = .71).
In analyzing differences in length of hospital stay for patients, the researchers found that, again, there was no statistically significant difference. In patients taking the reference without chemotherapy, the median length of stay was 18.5 days (interquartile range [IQR], 17.0-21.0) compared with 19.0 days (IQR, 17.0-22.0) for patients taking the biosimilar without chemotherapy (P = .10). For patients also taking chemotherapy, lengths of hospital stays increased, but not in a statistically significant manner.
Based on these findings, the researchers determined that, when using either the biosimilar or the reference product for ASCT, each medication has similar efficacy. The study authors concluded that, due to the similar efficacy, prescribing a biosimilar over a reference product would be able to “provide substantial cost savings to the healthcare system.”
Stakiw J, Sabry W, Elemary M, et al. Biosimilar G-CSF versus originator G-CSF for autologous peripheral blood stem cell mobilization: a comparative analysis of mobilization and engraftment. Presented at the 60th Annual Meeting and Exposition of the American Society of Hematology, December 1-4, 2018; San Diego, California. Abstract 3345. ash.confex.com/ash/2018/webprogram/ Paper115341.html.