Pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjects
Abstract A pharmacodynamics (PD) and immunogenicity study was conducted to investigate biosimilarity of Pelmeg®, a pegfilgrastim biosimilar to EU‐authorized Neulasta®. The multiple‐dose, randomized, double‐blind, two‐sequence, and three‐period cross‐over study comprised 96 healthy male subjects, rec...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-10-01
|
| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.507 |
| _version_ | 1818607826904285184 |
|---|---|
| author | Hendrik Wessels Dirk Lehnick Josef Höfler Ruediger Jankowsky Paul Chamberlain Karsten Roth |
| author_facet | Hendrik Wessels Dirk Lehnick Josef Höfler Ruediger Jankowsky Paul Chamberlain Karsten Roth |
| author_sort | Hendrik Wessels |
| collection | DOAJ |
| description | Abstract A pharmacodynamics (PD) and immunogenicity study was conducted to investigate biosimilarity of Pelmeg®, a pegfilgrastim biosimilar to EU‐authorized Neulasta®. The multiple‐dose, randomized, double‐blind, two‐sequence, and three‐period cross‐over study comprised 96 healthy male subjects, receiving Pelmeg (Test [T]) and Neulasta (Reference [R]) in a sequential manner (T‐T‐R vs R‐R‐T). Subjects were dosed with 3 mg pegfilgrastim, as this dose was previously shown to be in the ascending part of the dose‐response curve for PD. The primary PD endpoint was the area under the effect curve (AUEC0‐last) for absolute neutrophil count (ANC). The primary immunogenicity endpoint was proportion of anti‐drug antibody (ADA)‐positive subjects at the end of Period 2 (ie, after administration of two doses of the same study drug). Comparability was demonstrated for the PD endpoint, with the geometric mean ratio (T/R) of AUEC0‐last being 101.59%, with a corresponding 95% CI of [99.58; 103.63]. Of note, when using tighter acceptance limits (90.00%‐111.00%), comparability between test and reference was shown as well. Only two confirmed ADA positive samples were detected, one after treatment with Pelmeg and one after Neulasta. These had a low ADA titer, no filgrastim reactivity, and no neutralizing capacity. No clinically meaningful differences in safety between Pelmeg and Neulasta were observed. Overall, the results from this study confirmed the biosimilarity of Pelmeg and Neulasta for PD and immunogenicity, as shown already at the bioanalytical level and in the pivotal PK/PD study with Pelmeg. |
| first_indexed | 2024-12-16T14:32:56Z |
| format | Article |
| id | doaj.art-d76642d8346b4e2591c330a1e54cb714 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-12-16T14:32:56Z |
| publishDate | 2019-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-d76642d8346b4e2591c330a1e54cb7142022-12-21T22:28:11ZengWileyPharmacology Research & Perspectives2052-17072019-10-0175n/an/a10.1002/prp2.507Pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjectsHendrik Wessels0Dirk Lehnick1Josef Höfler2Ruediger Jankowsky3Paul Chamberlain4Karsten Roth5Cinfa Biotech GmbH (now part of the Mundipharma network of independent associated companies) Munich GermanyUniversity of Lucerne Lucerne SwitzerlandStaburo GmbH Munich GermanyCinfa Biotech GmbH (now part of the Mundipharma network of independent associated companies) Munich GermanyNDA Advisory Services, Ltd, Grove House Leatherhead Surrey UKCinfa Biotech GmbH (now part of the Mundipharma network of independent associated companies) Munich GermanyAbstract A pharmacodynamics (PD) and immunogenicity study was conducted to investigate biosimilarity of Pelmeg®, a pegfilgrastim biosimilar to EU‐authorized Neulasta®. The multiple‐dose, randomized, double‐blind, two‐sequence, and three‐period cross‐over study comprised 96 healthy male subjects, receiving Pelmeg (Test [T]) and Neulasta (Reference [R]) in a sequential manner (T‐T‐R vs R‐R‐T). Subjects were dosed with 3 mg pegfilgrastim, as this dose was previously shown to be in the ascending part of the dose‐response curve for PD. The primary PD endpoint was the area under the effect curve (AUEC0‐last) for absolute neutrophil count (ANC). The primary immunogenicity endpoint was proportion of anti‐drug antibody (ADA)‐positive subjects at the end of Period 2 (ie, after administration of two doses of the same study drug). Comparability was demonstrated for the PD endpoint, with the geometric mean ratio (T/R) of AUEC0‐last being 101.59%, with a corresponding 95% CI of [99.58; 103.63]. Of note, when using tighter acceptance limits (90.00%‐111.00%), comparability between test and reference was shown as well. Only two confirmed ADA positive samples were detected, one after treatment with Pelmeg and one after Neulasta. These had a low ADA titer, no filgrastim reactivity, and no neutralizing capacity. No clinically meaningful differences in safety between Pelmeg and Neulasta were observed. Overall, the results from this study confirmed the biosimilarity of Pelmeg and Neulasta for PD and immunogenicity, as shown already at the bioanalytical level and in the pivotal PK/PD study with Pelmeg.https://doi.org/10.1002/prp2.507biosimilarsfilgrastimhighly similarmyelosuppressive chemotherapyneutropeniaoncology |
| spellingShingle | Hendrik Wessels Dirk Lehnick Josef Höfler Ruediger Jankowsky Paul Chamberlain Karsten Roth Pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjects Pharmacology Research & Perspectives biosimilars filgrastim highly similar myelosuppressive chemotherapy neutropenia oncology |
| title | Pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjects |
| title_full | Pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjects |
| title_fullStr | Pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjects |
| title_full_unstemmed | Pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjects |
| title_short | Pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjects |
| title_sort | pharmacodynamics safety and immunogenicity of pelmeg r a pegfilgrastim biosimilar in healthy subjects |
| topic | biosimilars filgrastim highly similar myelosuppressive chemotherapy neutropenia oncology |
| url | https://doi.org/10.1002/prp2.507 |
| work_keys_str_mv | AT hendrikwessels pharmacodynamicssafetyandimmunogenicityofpelmegapegfilgrastimbiosimilarinhealthysubjects AT dirklehnick pharmacodynamicssafetyandimmunogenicityofpelmegapegfilgrastimbiosimilarinhealthysubjects AT josefhofler pharmacodynamicssafetyandimmunogenicityofpelmegapegfilgrastimbiosimilarinhealthysubjects AT ruedigerjankowsky pharmacodynamicssafetyandimmunogenicityofpelmegapegfilgrastimbiosimilarinhealthysubjects AT paulchamberlain pharmacodynamicssafetyandimmunogenicityofpelmegapegfilgrastimbiosimilarinhealthysubjects AT karstenroth pharmacodynamicssafetyandimmunogenicityofpelmegapegfilgrastimbiosimilarinhealthysubjects |