CHMP Issues Positive Opinion on Pegfilgrastim Biosimilar


The European Medicines Agency's Committee for Medicinal Products for Human Use has recommended approval of their pegfilgrastim biosimilar.

Mark Levick, MD, PhD

Mark Levick, MD, PhD, MD

Mark Levick, MD, PhD

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended approval of their biosimilar for pegfilgrastim (Neulasta), announced Sandoz, the manufacturer of filgrastim-sndz.

Sandoz is seeking an indication for their pegilgrastim biosimilar (Ziextenzo) to prevent febrile neutropenia in patients receiving myelosuppressive chemotherapy, those with acute myeloid leukemia receiving induction or consolidation chemotherapy, patients with cancer undergoing bone marrow transplantation, those undergoing autologous peripheral blood progenitor cell collection and therapy, and those with severe chronic neutropenia. These are the same proposed indications as reference pegfilgrastim.

If approved by the European Commission, the biosimilar will be available for use in the 28 countries of the European Union.

“While pegfilgrastim is a proven effective and safe treatment for febrile neutropenia-related infections, many cancer patients throughout Europe are not treated with this medicine,” said Mark Levick MD, PhD, Sandoz Global Head of Development, Biopharmaceuticals. “Our biosimilar medicine is expected to match the reference medicine in terms of safety, efficacy and quality. If approved, we will do our best to provide this critically important option to all patients who stand to benefit from it.”

In March 2015, filgrastim-sndz became the first biosimilar to receive FDA approval. Moreover, the agent was approved for all 5 indications of filgrastim. In July 2018, the FDA approved a second filgrastim biosimilar, filgrastim-aafi (Nivestym) for the same indications. Pegfilgrastim is a long-acting version of filgrastim (Neupogen); the proposed indication of pegfilgrastim as a leukocyte growth factor is intended to reduce duration of neutropenia and the incidence of febrile neutropenia due to chemotherapy.

Previous for The CHMP’s decision was based in part on findings presented at the 2017 San Antonio Breast Cancer Symposium. In a single-dose, randomized, double-blind, 2-way crossover study, the biosimilar demonstrated similar pharmacokinetics, pharmacodynamics, immunogenicity, and safety as reference pegfilgrastim.1

Regarding, filgrastim-sndz, the pivotal double-blind phase III PIONEER trial (NCT01519700) was the key clinical study that was the FDA of that biosimilar's FDA approval. All patients received 6 cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy and were randomized to either 6 cycles of EP2006, 6 cycles of filgrastim, or one of two 6-cycle regimens that rotated between the two drugs.2

Investigators administered filgrastim or filgrastim-sndz subcutaneously at 5 mcg/kg body weight starting on day 2 of cycle 1 and given until the absolute neutrophil count (ANC) recovered to 10 Gi/L after the nadir or a maximum of 14 days, whichever came first.

The primary endpoint was duration of severe neutropenia (DSN), which the researchers defined as the number of consecutive days a patient’s ANC was <0.5 Gi/L after the first cycle of chemotherapy. For this analysis, which included 204 patients, the researchers combined all patients who received filgrastim-sndz (n = 101) in the first cycle and compared them with all those who received filgrastim (n = 103) in the first cycle.

The cycle 1 mean DSN was 1.17 and 1.20 days, for filgrastim-sndz and filgrastim, respectively. The mean time to ANC recovery in cycle 1 was 1.8 days ± 0.97 in the filgrastim-sndz arm compared with 1.7 days ± 0.81 in the filgrastim arm.

Lee Schwartzberg, MD, served as lead author for a recently published retrospective analysis that showed that the incidence of febrile neutropenia was statistically equivalent for patients with nonmyeloid cancer who received filgrastim-sndz (n = 162) and those who received the filgrastim biologic (filgrastim-ref; n = 3297) during their first chemotherapy cycle.3

Schwartzberg et al defined febrile neutropenia based on codes for neutropenia and fever (N/F), neutropenia and infection (N/I), and neutropenia, infection, and fever (N/I/F). Incidence of febrile neutropenia was 1.4% in the filgrastim-sndz group compared with 0.9% in the filgrastim-ref cohort for N/F, 2.3% versus 1.7% for N/I, and 0.0% versus 0.3% for N/I/F, respectively.

“We found that there was no difference, statistically, between the incidences of febrile neutropenia, defined a couple of different ways, between the group that received filgrastim-sndz versus the standard originator filgrastim,” Schwartzberg said in an August interview with OncLive. “The incidence of febrile neutropenia was low in both groups. We defined febrile neutropenia based on a sample from a managed care population that was a billing claims analysis sample. Using a variety of techniques to both assess the claims and to adjust for differences between the populations using propensity scores, we were able to see there was no difference.”


  1. Nakov R, Gattu S, Wang J, Velinova M, Skerjanec A. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects. Cancer Res. 2018;78(4 suppl):Abstract nr P3-14-10.
  2. Blackwell K, Semiglazov V, Gascon P, et al. A Comparison of Proposed Biosimilar and Originator Filgrastim for the Prevention of Neutropenia in Patients with Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Phase III, Randomized, Double-Blind Trial (The PIONEER study). Blood. 2014;124(21):5133-5133.
  3. Schwartzberg L, Lal L, Balu S, et al. Clinical outcomes of treatment with filgrastim versus filgrastim biosimilar and febrile-neutropenia-associated costs among patients with nonmyeloid cancer undergoing chemotherapy [published online ahead of print April 24, 2018]. J Manag Care Spec Pharm. doi: 10.18553/jmcp.2018.17447
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