Multiple biosimilars of pegfilgrastim are available in both the United States and Europe, and the field of competitors to Amgen’s brand-name Neulasta continues to expand. During the 2019 American Society of Clinical Oncology Annual Meeting, 3 research teams shared their findings on biosimilar pegfilgrastim development programs from sponsors Sandoz, Fresenius Kabi, and Gema Biotech.
Multiple biosimilars of pegfilgrastim are available in both the United States and Europe, and the field of competitors to Amgen’s brand-name Neulasta continues to expand. During the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, 3 research teams shared their findings on biosimilar pegfilgrastim development programs from sponsors Sandoz, Fresenius Kabi, and Gema Biotech.
Sandoz’s pegfilgrastim biosimilar is already approved in the European Union, where it received a marketing authorization in November 2018 under the name Ziextenzo. In the United States, however, its Biologics License Application (BLA) is pending with the FDA after the product received a previous Complete Response Letter. The newly resubmitted BLA includes new data from a pivotal pharmacokinetic (PK) and pharmacodynamic (PD) study, data from which were published to coincide with the ASCO meeting.1
The study sought to confirm the PK and PD similarity of the biosimilar with the US-licensed reference and to establish a bridge between the US and EU references. It was designed as a randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover study in 577 healthy volunteers. The study was powered (90%) to achieve CIs within a biosimilarity margin of 0.8-1.25 in pairwise comparisons.
The 90% CIs of the geometric mean ratios were all contained within the prespecified biosimilarity margin for parameters of area under the curve (AUC) 0-inf, AUC0-last, maximum observed concentration (Cmax), area under effect curve of absolute neutrophil counts (ANC AUEC0-last), and ANC for the maximum response achievable (Emax).
According to the authors, this study demonstrated the PK and PD similarity of the biosimilar with both the US and EU references.
Fresenius Kabi’s proposed pegfilgrastim biosimilar, MSB11455, was also the subject of new data published to coincide with the ASCO meeting.
The proposed biosimilar was assessed in a phase 1 study that assessed the PK and PD similarity between the biosimilar and the reference. A total of 244 healthy volunteers were randomized 1:1 to receive 1 of 2 crossover sequences: single subcutaneous doses of the biosimilar followed by the reference, or the reference followed by the biosimilar.
For all PK and PD parameters—AUC0—∞, AUC0—last, Cmax, Emax, and AUE0—t—the 90% CIs of the geometric mean ratios were contained within the prespecified equivalence margin of 80.00%—125.00%, and safety, tolerability, and immunogenicity were comparable between the 2 treatment sequences. No filgrastim-specific neutralizing antibodies were detected in either sequence.
According to the authors, these data support the biosimilarity of MSB11455 to the reference.
Gema Biotech’s pegfilgrastim product, approved in Latin American countries including Argentina, was studied in a randomized, multicenter clinical trial in patients with breast cancer who were scheduled to receive 4 to 6 cycles of chemotherapy.3
In total, 120 patients were randomized to receive the biosimilar (n = 58) or the reference (n = 62).
The investigators found that patients developed severe neutropenia (SN) in 18.4% of cycles using the biosimilar and in 16.2% of cycles using the reference. In cycle 1, 16 patients in the biosimilar arm and 11 patients in the reference arm developed SN.
In the per protocol analysis, the mean duration of SN in the first cycle was 0.78 (±1.53) days for the biosimilar arm and 0.53 (±1.25) days the reference group; the prespecified noninferiority margin for the duration of SN had been set at less than 1 day.
Seven adverse events (AEs) were reported in the biosimilar arm versus 31 in the reference arm. The most common AE was myalgia.
Based on the noninferiority margin that had been predetermined, say the investigators, the data support the claim that the product is biosimilar to the reference.
1. Otto GP, Nakov R, Schussler S, et al. A large multicenter, randomized, double-blind, crossover study in healthy volunteers, comparing pharmacokinetics and pharmacodynamics of Sandoz proposed biosimilar pegfilgrastim with European and United States reference pegfilgrastim. Presented at: American Society of Clinical Oncology Annual Meeting 2019; May 31-June 4, 2019; Chicago, Illinois. Abstract e23118.
2. Lickliter JD, Griffin P, Vincent E, et al. Pharmacokinetic/pharmacodynamic assessment of a proposed biosimilar MSB11455 versus the currently licensed pegfilgrastim: a randomized, double-blind trial. Presented at: American Society of Clinical Oncology Annual Meeting 2019; May 31-June 4, 2019; Chicago, Illinois. Abstract e14514.
3. Richardet ME, Kowalyszyn RD, Valera MS, et al. A randomized, multicenter clinical trial to determine the efficacy and safety of pegfilgrastim (GEMA BIOTECH) compared to pegfilgrastim (Roche) for prevention of chemotherapy induced neutropenia in patients with breast cancer. Presented at: American Society of Clinical Oncology Annual Meeting 2019; May 31-June 4, 2019; Chicago, Illinois. Abstract 3113.