This week, a pair of papers detailing the clinical program for the biosimilar appeared in Pharmacology Research and Perspectives.
In 2018, the European Commission authorized Cinfa Biotech and Mundipharma’s biosimilar pegfilgrastim, Pelmeg, for all indications of the reference Neulasta. The biosimilar has since launched in markets including the United Kingdom, Germany, the Netherlands, and Ireland.
This week, a pair of papers detailing the clinical program for the biosimilar appeared in Pharmacology Research and Perspectives. The first paper described a pharmacokinetic (PK) and pharmacodynamic (PD) study that sought to demonstrate comparability of the biosimilar to the EU-licensed reference.1
The study was a randomized, double-blind, single-dose, 2-way crossover study in 171 healthy male volunteers. The patients were randomized to receive 6-mg doses of either the biosimilar followed by the reference or the reference followed by the biosimilar.
The primary PK endpoints were area under the concentration curve from time zero to last measurable concentration (AUC0‐last) and maximum concentration (Cmax); the confidence intervals for the ratios of the biosimilar and the reference were fully contained within the prespecified equivalence margin of 80% to 125% for both AUC0‐last (95.2%; 94.3% CI, 86.6%-104.7%) and Cmax (92.8%; 94.3% CI, 84.4%-102.2%).
The primary PD endpoint was the area under the effect curve (AUEC0‐last) for absolute neutrophil count (ANC). The geometric mean ratio of AUEC0‐last was approximately 100% and the corresponding 95% CI was also approximately 100%.
All of the subjects were assessed for safety; in total, 90.6% of subjects reported any adverse event (AE). Most commonly reported were back pain, headache, and nasopharyngitis. Overall, 19.9% of patients had anti-drug antibodies to pegfilgrastim.
The second paper described a study that sought to confirm the PD similarity between the biosimilar and the reference at a more sensitive dose, and to investigate potential differences in immunogenicity.2
This randomized, double-blind, multiple-dose, 3-period, 2-sequence crossover study was also conducted in healthy male volunteers. A total of 96 volunteers were enrolled, and they were randomized to receive either a treatment sequence comprising a 3-mg dose of the reference, followed by the reference, followed by the biosimilar or a 3-mg dose of the biosimilar, followed by the biosimilar, followed by the reference.
The primary PD endpoint was AUEC0‐last for ANC, and the primary immunogenicity endpoint was the proportion subjects who developed ADAs at the end of the second administration of the same study drug (ie, after the second dose in the 3-dose sequence).
Comparability was demonstrated for the PD endpoint, with the geometric mean ratio of AUEC0‐last of 101.59% (95% CI, 99.58%-103.63%) falling within the same prespecified equivalence margin as described in the first study.
In total, 2 subjects, 1 from each treatment sequence, were positive for ADAs. Both samples were of low titer, and no neutralizing antibodies were detected.
Safety was also assessed; 95.8% of subjects experience any AE, and the proportion of subjects experiencing AEs was comparable between patients who were receiving the biosimilar or the reference at the time. Injection-site reactions were reported for 1 subject receiving the biosimilar and for 3 subjects receiving the reference.
According to the authors, these results, taken together with the findings from the first study, confirm the biosimilarity of Pelmeg with the EU-authorized Neulasta.
1. Roth K, Lehnick D, Wessels H, Höfler J, Gastl B, Jankowsky R. Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of Pelmeg, a pegfilgrastim biosimilar in healthy subjects [published online August 13, 2019]. Pharmacol Res Perspect. doi: 10.1002/prp2.503.
2. Wessels H, Lehnick D, Höfler J, Jankowsky R, Chamberlain P, Roth K. Pharmacodynamics, safety, and immunogenicity of Pelmeg, a pegfilgrastim biosimilar in healthy subjects [published online August 13, 2019]. Pharmacol Res Perspect. doi: 10.1002/prp2.507.