Biosimilar Approval Pathway Research Articles

The US Biosimilars Act

Ever since the signing of the US healthcare reform legislation, the Patient Protection and Affordable Care Act (PPAC), speculation as to what a US FDA biosimilar programme might look like has been rife. Now the FDA has published guidance documents on biosimilar product development, which has been described by Dr Janet Woodcock, MD, Director of the FDA’s Center for Drug Evaluation and Research, as “an innovative approach to supporting the development of biosimilars at every step of the process.” Nevertheless, these initial guidelines are rather general in nature, so the looming question remains as to what extent the US biosimilar pathway will represent a viable route to market. The pathway for resolution of inevitable patent disputes is long and torturous and it seems that it will inevitably result in delays and litigation; the impact and implications of this represents a key consideration in the choice of the regulatory pathway. Thus, if there are no benefits in terms of reduced data requirement, a more rapid route to market and benefits to market access with the biosimilar route, then one really would have to question the value of this route. As far as whether the biosimilar pathway will offer reduced data requirements, the jury is still out. Initial indications suggest that the FDA review divisions might initially take a more conservative stand, but one might expect that, as policy becomes more transparent and with the publication of the guidelines, a more pragmatic position might emerge. One of the most controversial concepts raised by the Biologics Price Competition and Innovation Act of 2009 (BPCI) is that of interchangeability between the innovator and the biosimilar product. This presents a very high bar and in many instances may simply not be achievable or financially viable. Yet, without interchangeable status, a biosimilar will be no different to any other biological approved through a standalone route and, inevitably, an extensive marketing effort would be required to achieve any meaningful market penetration. On the other hand, a standalone application may not offer a viable alternative either, as this would require a more conventional and graduated development programme with the need for extensive non-clinical and phase II data. Furthermore, the inability to extrapolate between indications would require large comparative trials for each indication. Biosimilars are an essential and inevitable part of enhancing patient access to life-saving medications, and if nations want to maximize the value of healthcare spend, bringing health and well-being to their citizens, biosimilars are a necessity and their exclusion an unaffordable luxury. Thus, one would anticipate that, inevitably, despite the debate, the BPCI will spawn an attractive US biosimilar approval pathway. Certainly, there are many sponsors of biosimilar products banking on just that and the recently published guidelines suggest that the FDA will ultimately apply sound scientific principles, which is, undoubtedly, the optimal way forward.

Optimizing the Approval Pathway for Biosimilars to Treat Psoriasis and Psoriatic Arthritis

Optimizing the Approval Pathway for Biosimilars to Treat Psoriasis and Psoriatic Arthritis

Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple intravenous administrations: an open-label randomised controlled trial

BackgroundHX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway. Therefore, in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa, the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations.MethodsAn open, randomised, parallel group study was conducted in 80 healthy adult males. Subjects were randomised to multiple intravenous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa three-times-weekly for four weeks. Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay and pharmacokinetic parameters for the two treatments were compared. The time course and area under the effect curve ratio of haematological characteristics were used as surrogate parameters for efficacy evaluation.ResultsThe haematological profiles of both treatments were similar, as determined from their population mean curves and the AUECHb ratio and 90% confidence interval (99.9% [98.5–101.2%]), the primary pharmacodynamic endpoint of this study. The pharmacokinetic parameters after the treatments showed minor differences after single dosing, but not at steady state doses. After multiple doses, HX575 was bioequivalent to the comparator with respect to the rate and extent of exposure of exogenous epoetin (AUCτ ratio and 90% confidence interval: 89.2% [82.5–96.2%]). Study medication was well tolerated with no clinically relevant differences between safety profiles of the treatments. Anti-epoetin antibodies were not detected.ConclusionHX575 and the comparator epoetin alfa were bioequivalent at steady state circulating drug concentrations with respect to their pharmacokinetic profile and pharmacodynamic action. This supports the conclusion that HX575 and the comparator epoetin alfa, when administered intraveneously, will be equally efficacious and may be interchangeable as therapy.