Pelmeg, a biosimilar pegfilgrastim developed in the context of evolving regulatory guidelines

Pelmeg® is a biosimilar pegfilgrastim, which obtained European Union (EU) regulatory approval in September 2018, with market- ing beginning in January 2019. A comprehensive analytical, functional and preclinical comparability programme demonstrated a high degree of similarity between Pelmeg® and its reference product Neulasta®. A targeted clinical development programme was conducted with Pelmeg®, consisting of two comparative pharmacokinetic (PK)/pharmacodynamic (PD) studies in healthy subjects. Since a surrogate endpoint for efficacy (absolute neutrophil count [ANC]) was available, efficacy and safety studies in patients were waived by the regulatory authorities. Clinical studies with Pelmeg® were designed in close dialogue with regulatory authorities in Europe. During the development process for Pelmeg®, the EU biosimilar guidelines, in particular relating to granu- locyte colony-stimulating factor (G-CSF), were modified. The development of Pelmeg® demonstrates that regular discussions with regulators, in the form of scientific advice or other interactions, are valuable opportunities for dialogue regarding scientific progress related to the comparability of biosimilars. Regulators – at least in the area of biosimilar development – were found to be open to improvements and to deviate from existing guidelines if there was agreement that the scientific state-of-the-art has superseded some aspect of the guidelines. Overall, we suggest that abridged development programmes waiving the need for phase III studies, as described for Pelmeg®, are possible, in particular if good surrogate endpoints are available. In line with this, the number of waivers for phase III studies in biosimilar development has increased in recent years.