Proposed biosimilar pegfilgrastim (LA-EP2006) compared with reference pegfilgrastim in Asian patients with breast cancer: an exploratory comparison from two Phase III trials

Abstract

aim: This is a pooled subgroup analysis of Asian patients enrolled in two Phase III confirmatory studies comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in women receiving chemotherapy for breast cancer. Patients & methods: Women were randomized to LA-EP2006 (n = 90) or reference (n = 84) pegfilgrastim (Neulasta®, Amgen, Inc., CA, USA) for ≤6 cycles of TAC chemotherapy. Primary end point was duration of severe neutropenia during Cycle 1 (number of consecutive days with absolute neutrophil count <0.5 × 10 9 /l) with equivalence confirmed if 95% CIs were within a ±1-day margin. Results: Mean duration of severe neutropenia (days) in Cycle 1 was 1.36 ± 0.98 (LA-EP2006) versus 1.35 ± 1.06 (reference) (difference 0.01 days; 95% CI: -0.30-0.32, indicating equivalence). conclusion: LA-EP2006 showed similar clinical efficacy and safety compared with reference pegfilgrastim.

Proposed biosimilar pegfilgrastim shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects

“…As the PD marker, ANC is a clinically relevant surrogate marker of efficacy in clinical practice; the similar PD profiles reported here support the findings of clinical equivalence from the phase III efficacy and safety studies of Sandoz proposed biosimilar pegfilgrastim and reference pegfilgrastim in cancer patients .…”

“…Study assessments PK assessments. In each period, PK blood samples (4 ml each) were collected from subjects predose (-15 min) and then at 4,8,12,24,36,48,60,72,84,96,108,120,144,168,192,216,264 and 336 h postdose. Blood samples were collected into serum separator tubes and stored at ≤-70°C until analysis.…”

“…Physicochemical and functional characterization using state‐of‐the‐art analytical procedures showed Sandoz proposed biosimilar pegfilgrastim to be highly similar to the reference pegfilgrastim (Neulasta ® , Amgen), which has been marketed in the EU and in the USA since 2002. In two confirmatory, randomized, double‐blind, phase III studies in patients with breast cancer (PROTECT‐1 and PROTECT‐2), Sandoz proposed biosimilar pegfilgrastim showed no clinically meaningful differences in efficacy and safety to reference pegfilgrastim (Neulasta ® ) .…”

Meta‐analysis of Pharmacokinetic/Pharmacodynamic Results of 3 Phase 1 Studies with Biosimilar Pegfilgrastim

“…Importantly, the 90%CIs for the ratio between the biosimilar and reference pegfilgrastim remained within the predefined biosimilarity margins for all primary PK parameters, and the slightly higher exposure did not translate into any differences in PD effects in the present study. Furthermore, no clinically meaningful differences in efficacy and safety have been observed between Sandoz biosimilar pegfilgrastim, US‐reference pegfilgrastim, and EU‐reference pegfilgrastim in the 3 separate phase 3 clinical trials, providing further confirmation that this small difference in exposure does not translate into clinical relevance 6–9 . Phase 3 confirmatory studies comparing Sandoz biosimilar pegfilgrastim with reference pegfilgrastim showed that the mean duration of severe neutropenia in the first chemotherapy cycle (primary end point) was similar between the groups (1.05 ± 1.06 vs 1.01 ± 0.96 days), with a treatment difference of −0.04 days (95%CI, −0.19 to 0.11) that met the equivalence criteria (95%CIs within the defined margin of ±1 day) 6–8 .…”

“…Both studies demonstrated the therapeutic equivalence of Sandoz biosimilar and reference pegfilgrastim, as assessed by the duration of severe neutropenia during cycle 1 as the primary end point 5–7 . Subsequent pooled analyses of results from the 2 studies showed no clinically meaningful efficacy and safety differences between the 2 biologics and also among patients of Asian origin 8,9 …”