Comparison of Efficacy and Safety of Lupin’s Pegfilgrastim with Neulastim® as an Adjunct to Chemotherapy in Patients with Non Myeloid Malignancies: A Randomised Phase III Clinical Study

Abstract

Introduction: Pegfilgrastim is indicated in patients receiving myelosuppressive anticancer drugs to reduce the Duration of Severe Neutropenia (DSN) and incidence of Febrile Neutropenia (FN). The efficacy and safety of a proposed Pegfilgrastim biosimilar should be compared with an approved biologic drug to establish therapeutic equivalence. Aim: To compare the efficacy of Lupin’s biosimilar Pegfilgrastim versus Neulastim® (Amgen Inc.) as an adjunct to chemotherapy in patients with non-myeloid malignancies. Materials and Methods: The present prospective, open-label, randomised phase lll clinical study was conducted on a total of 170 patients with histologically or cytologically confirmed non-myeloid malignancies eligible to receive a myelosuppressive chemotherapy regimen. The participants were administered Lupin’s Pegfilgrastim (n=86) or Neulastim® (n=84) 6 mg by subcutaneous injection, once in each chemotherapy cycle for a maximum of three cycles. Patients were chemotherapy naive or had not received myelosuppressive chemotherapy within last 12 months of screening. The primary efficacy endpoint was DSN (number of days on which absolute neutrophil count <0.5×109/L) in cycle 1 of chemotherapy. Equivalence was confirmed, if 95% Confidence Intervals (CI) were within the equivalence margin of ±1 day. Safety evaluation included assessment of Adverse Events (AEs), rate of discontinuation due to AEs, vital signs, and laboratory parameters. Statistical analysis were done using SAS Enterprise guide 9.4 (SAS Institute Inc., Cary, 2000). Results: Of the 170 patients balanced for demographic characteristics, 161 patients completed cycle 1, 151 patients completed cycle 2, and 142 patients completed cycle 3. The mean±Standard Deviation (SD) DSN in cycle 1 was 0.127±0.5533 days with Pegfilgrastim (n=63) and 0.197±0.6615 days with Neulastim® (n=66) in the Per Protocol (PP) assessment; and 0.174±0.636 days with Pegfilgrastim and 0.193±0.671 days with Neulastim® in the modified Intent-to-Treat (mITT) assessment. The mean DSN between the groups did not differ significantly (PP: p=0.5167, mITT: p=0.8554). The 95% CI of difference in mean DSN in PP (-0.2796 to 0.1481) and mITT (-0.2103 to 0.1889) assessments was contained within the predefined equivalence margin of ±1 day. Secondary outcomes and safety profiles were also comparable between the two groups. Conclusion: The present study establishes Lupin’s Pegfilgrastim as a therapeutically equivalent biosimilar alternative to Neulastim® in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy.

Keywords

• absolute neutrophil count
• biosimilars
• febrile neutropenia
• granulocyte colony-stimulating factor
• therapeutic equivalence