Recently published in AJKD is a timely perspective by Fishbane et al of the emerging role of biosimilar erythropoiesis-stimulating agents (ESAs) in US nephrology practice. The context is the upcoming expiration of the patent on epoetin alfa (Epogen™/Procrit™) in the US (European patent expired in 2004). A biosimilar is a non-branded copy of a biologic drug that is highly similar to the reference product. There may, however, be minor differences in clinically inactive components, but no clinically relevant differences in terms of purity, safety, and efficacy to the reference product. Biosimilar ESAs are expected to be approved by the FDA and arrive on the US market in 2015. Biosimilars play an important role in keeping healthcare costs manageable, but open some theoretical concerns regarding their use. Some issues highlighted by the authors include:
- Batch-to-batch variability (although this may also be evident with the reference biologic product).
- Lack of as rigorously proven efficacy and safety profile compared to the originator product.
- With particular regards to ESAs, the possible development of neutralizing antibodies with subsequent red cell aplasia. This has not been an issue in Europe thus far (including in post-authorization safety analysis).
- Biosimilars produced in countries with different regulatory processes. For example, many biosimilars are produced in Korea, India, and China (including varying glycosylation patterns and high molecular weight species, which may be more immunogenic).
The authors describe the abbreviated, yet stringent, FDA regulatory processes for approval of biosimilar agents. They also discuss various biosimilar ESAs being readied for the US market. Despite concerns, the authors state that the “overwhelming body of evidence from clinical studies and 7 years of use in clinical practice in Europe has demonstrated that the efficacy and safety profile of biosimilar epoetins developed under an appropriately stringent regulatory framework is highly similar to that of originator ESA.”
The introduction of biosimilar ESAs to the US comes a decade after the European patents ran out. In that time, we have witnessed the withdrawal of peginesatide and the CHOIR, CREATE, and TREAT trials dampen our enthusiasm for aggressive ESA use. The authors speculate whether this may affect uptake of biosimilar ESAs in the US compared to Europe. Another issue that may affect biosimilar ESA uptake is the continued development of novel anti-anemia agents for CKD (e.g. HIF stabilizers). These will hopefully provide more variety and competition in the market. Overall, the potential economic benefits of biosimilar ESAs appear clear, especially to US dialysis providers in the era of bundling. We wait to see how this develops in 2015.
Dr. Paul Phelan
AJKD Blog Contributor