A pharmacokinetics and pharmacodynamics equivalence trial of the proposed pegfilgrastim biosimilar, MYL-1401H, versus reference pegfilgrastim

Waller, Christiane; Tiessen, Renger G.; Lawrence, Tracey; Shaw, Andrew; Liu, Mark Shiyao; Sharma, Rajiv; Baczkowski, Mark; Kothekar, Mudgal; Micales, Catherine E.; Barve, Abhijit; Ranganna, Gopinath; Pennella, Eduardo J.

doi:10.1007/s00432-018-2643-3

Cited by 29 publications

(32 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Robust and correlative PK/PD studies are sensitive at detecting subtle differences in biosimilar efficacy. Previous PK/PD analysis of MYL-1401H demonstrated equivalence with reference pegfilgrastim [ 18 ], consistent with efficacy data from this study.…”

Section: Discussionsupporting

confidence: 89%

“…Pegfilgrastim was approved in 2002 for CIN prophylaxis, and significant research has gone into pegfilgrastim biosimilar development [ 3 ]. Recent preclinical and PK/PD data have supported biosimilarity between originator pegfilgrastim (Neulasta®; Amgen Inc., Thousand Oaks, CA) and the proposed biosimilar MYL-1401H [ 18 ]. Here, we present data from a phase 3 efficacy and safety trial conducted to confirm equivalence of MYL-1401H with European Union (EU)–sourced reference pegfilgrastim for CIN prophylaxis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia

et al. 2019

Self Cite

View full text Add to dashboard Cite

Pegfilgrastim is indicated for reducing the duration of neutropenia and incidence of febrile neutropenia in patients receiving cytotoxic chemotherapy. Here, safety and efficacy of MYL-1401H, a proposed pegfilgrastim biosimilar, were investigated as prophylaxis for chemotherapy-induced neutropenia. This was a phase 3, multicenter, randomized, double-blind, parallel-group equivalence trial of MYL-1401H vs European Union–sourced reference pegfilgrastim. Patients with newly diagnosed stage II/III breast cancer eligible to receive (neo) adjuvant chemotherapy with docetaxel/doxorubicin/cyclophosphamide every 3 weeks for 6 cycles were enrolled and randomized 2:1 to 6 mg of MYL-1401H or reference pegfilgrastim 24 h (+ 2-h window after the first 24 h) after the end of chemotherapy. The primary efficacy endpoint was the duration of severe neutropenia in cycle 1 (i.e., days with absolute neutrophil count (ANC) < 0.5 × 10 9 /L). Mean (standard deviation (SD)) duration of severe neutropenia in MYL-1401H and reference pegfilgrastim groups was 1.2 days (0.93) and 1.2 days (1.10), respectively. The 95% CI for least squares mean difference (− 0.285, 0.298) was within the predefined equivalence range of ± 1 day. Secondary endpoints, including grade ≥ 3 neutropenia (frequency, 91% and 82% for MYL-1401H and reference pegfilgrastim, respectively), time to ANC nadir (mean (SD), 6.2 (0.98) and 6.3 (1.57) days), and duration of post-nadir recovery (mean (SD), 1.9 (0.85) and 1.7 (0.91) days) were comparable. Overall safety profiles of the study drugs were comparable. MYL-1401H demonstrated equivalent efficacy and similar safety to reference pegfilgrastim and may be an equivalent option for reducing incidence of neutropenia. ( ClinicalTrials.gov , NCT02467868; EudraCT, 2014-002324-27). Electronic supplementary material The online version of this article (10.1007/s00277-019-03639-5) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In 2018, the FDA approved the first pegfilgrastim biosimilars, pegfilgrastim-jmdb and pegfilgrastim-cbqv, for the same indications as pegfilgrastim based on data showing highly similar pharmacokinetics, pharmacodynamics, and safety in healthy volunteers. 10,12,[40][41][42][43][44] Pegfilgrastim-jmdb has been shown to have high analytical and functional similarity to pegfilgrastim, with similar structure, molecular mass, physicochemical characteristics, and G-CSF receptor binding affinity. 45,46 A phase I randomized equivalence trial concluded that pegfilgrastim-jmdb demonstrated similar pharmacokinetics, pharmacodynamics, and safety to pegfilgrastim in healthy volunteers.…”

Section: Filgrastim-aafimentioning

confidence: 99%

“…45,46 A phase I randomized equivalence trial concluded that pegfilgrastim-jmdb demonstrated similar pharmacokinetics, pharmacodynamics, and safety to pegfilgrastim in healthy volunteers. 40 In a multicenter randomized phase III efficacy and safety trial, patients with breast cancer receiving myelosuppressive chemotherapy with pegfilgrastim-jmdb support showed no difference in duration of severe neutropenia, time to absolute neutrophil count (ANC) nadir, duration of postnadir recovery, or treatment-related adverse events compared with patients receiving reference pegfilgrastim. 47 Pegfilgrastim-jmdb has also demonstrated low immunogenic potential in healthy volunteers and patients with cancer receiving myelosuppressive chemotherapy.…”

Section: Filgrastim-aafimentioning

confidence: 99%

NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020

Becker

Griffiths²,

Alwan

et al. 2020

Journal of the National Comprehensive Cancer Network

View full text Add to dashboard Cite

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

show abstract

“…This includes published Phase I studies demonstrating similar PK/PD, safety, and immunogenicity between reference biologic and Cinfa Biotech biosimilar pegfilgrastim (B12019/Pelmeg), 26,27 Accord Healthcare biosimilar pegfilgrastim (INTP5/Pelgraz), 28,29 and Mylan biosimilar pegfilgrastim (MYL-1401H/Fulphila). 30 Crossover designs were used to compare the biosimilar of pegfilgrastim to both EU-and US-reference biologics. 29 In summary, the primary objectives of this study were met, as PK and PD biosimilarity of Sandoz biosimilar pegfilgrastim with USand EU-reference biologics was achieved.…”

Section: Discussionmentioning

confidence: 99%

A large multicentre, randomized, double‐blind, cross‐over study in healthy volunteers to compare pharmacokinetics, pharmacodynamics and safety of a pegfilgrastim biosimilar with its US‐ and EU‐reference biologics

Bellon

Wang

Skerjanec

et al. 2020

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims: Recombinant PEGylated human granulocyte colony-stimulating factor (pegfilgrastim) is indicated for the reduction of chemotherapy-induced neutropenia and prevention of febrile neutropenia. Biosimilar pegfilgrastim is expected to reduce the financial burden of this complication of chemotherapy. The aim of this study was to demonstrate biosimilarity between Sandoz biosimilar pegfilgrastim and its US-and EU-approved reference biologics.Methods: Phase I, randomized, double-blind, single-dose, 3-period, 6-sequence cross-over, multicentre study to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of Sandoz biosimilar pegfilgrastim with US-and EUreferences in healthy adults.Results: Pharmacokinetic and pharmacodynamic similarity was demonstrated between the 3 biologics, as the 90% confidence interval for all primary pharmacokinetic and pharmacodynamic endpoint comparisons were contained within the predefined similarity margins of 0.80-1.25. Safety, immunogenicity and tolerability were also similar.Conclusions: Sandoz biosimilar pegfilgrastim demonstrated pharmacokinetic and pharmacodynamic similarity to both US-and EU-reference biologics. No meaningful differences in safety, local tolerability and immunogenicity were identified.

show abstract

A pharmacokinetics and pharmacodynamics equivalence trial of the proposed pegfilgrastim biosimilar, MYL-1401H, versus reference pegfilgrastim

Abstract: MYL-1401H demonstrated similar PK, PD, and safety to reference pegfilgrastim in healthy volunteers and may be an equivalent option for the prevention of febrile neutropenia.

Cited by 29 publications

References 18 publications

Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia

Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia

NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020

A large multicentre, randomized, double‐blind, cross‐over study in healthy volunteers to compare pharmacokinetics, pharmacodynamics and safety of a pegfilgrastim biosimilar with its US‐ and EU‐reference biologics

Contact Info

Product

Resources

About