Phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H vs EU-neulasta® in the prophylaxis of chemotherapy-induced neutropenia

Background

MYL-1401H is a proposed pegfilgrastim biosimilar to the reference product EU-Neulasta^®, based on physicochemical characterization, in vitro bioassays, toxicokinetics (TK), pharmacokinetics (PK), and pharmacodynamics (PD) studies.

Methods

This is a phase 3, multicenter, randomized, double-blind, parallel-group trial of MYL-1401H vs EU-Neulasta^®. Chemotherapy and radiotherapy naïve patients with newly diagnosed Stage II/III breast cancer were eligible to receive docetaxel, doxorubicin, and cyclophosphamide anti-cancer chemotherapy planned every 3 weeks for 6 chemotherapy cycles. A total of 194 patients were randomized in a 2:1 ratio to receive 6 mg/0.6 mL of either MYL-1401H or EU-Neulasta^® on Day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia (DSN) in Cycle 1, defined as days with absolute neutrophil count (ANC) 

Results

The mean ± SD DSN in the MYL-1401H and EU-Neulasta^® groups were 1.2 ± 0.93 and 1.2 ± 1.10, respectively. The 95% CI of least squares means difference [-0.285 day, 0.298 day] was within [-1 day, +1 day] range, that was also corroborated by the sensitivity analysis. Other endpoints of the study including Grade 3-4 neutropenia, time to ANC nadir, and duration of post-nadir recovery were comparable too. The overall safety profile of MYL-1401H was similar to EU-Neulasta^® with bone pain, an expected AE, as the most frequently reported treatment related TEAE.

Conclusions

MYL-1401H demonstrated equivalent efficacy to EU-Neulasta^® in the prophylaxis of chemotherapy induced neutropenia in patients with breast cancer. MYL-1401H was generally well tolerated and there were no particular safety concerns identified with overall safety profile being similar to EU-Neulasta^®.

Clinical trial identification

EudraCT Number: 2014-002324-27

Legal entity responsible for the study

Mylan GmbH

Funding

Mylan GmbH

Disclosure

C.F. Waller: Member of advisory board of Mylan. E. Pennella: Mylan Employee and stocks of Mylan. M. Bronchud: Member of consultant/advisory board of Mylan. R. Sharma: Currently employed by Mylan on full term permanent basis and also Mylan stock ownership. M. Baczkowski: Currently an employee of Mylan. In addition, financial relationship with employer in the form of stock options, restricted stock units, and shares of Mylan in retirement account. M. Kothekar: Full-time employee of Biocon Research Limited. A. Barve: Mylan full-time employee and stock in Mylan. All other authors have declared no conflicts of interest.