STIMUFEND® (pegfilgrastim-fpgk): Established biosimilarity to Neulasta® (pegfilgrastim)

Proven structural, functional, and clinical similarity1,2

  • STIMUFEND is FDA approved based on the totality of evidence supporting its biosimilarity to Neulasta

Confirmed bioequivalence to Neulasta1

PK parameters confirmed bioequivalence from post-dose

Graph showing bioequivalence of STIMUFEND® to Neulasta®

Arithmetic mean (SD) pegfilgrastim serum concentration time profiles after a single dose of pegfilgrastim in healthy subjects.

PD parameters confirmed bioequivalence over 16 days from post-dose

Graph showing PD parameters indicating bioequivalence of STIMUFEND® to Neulasta®

Arithmetic mean (SD) observed ANC-time profiles after a single dose of pegfilgrastim in healthy subjects.

  • STIMUFEND was assessed in healthy subjects in a double-blind, randomized, 2-sequence, 2-period, 2-treatment, crossover Phase I study (NCT03251248)1
  • 240 subjects received both treatments and were included in the PK/PD analysis sets
  • Primary PK endpoints were AUC from time zero to the last sampling time, AUC from time zero extrapolated to infinity, and Cmax
  • Primary PD endpoints were Emax and AUE from time zero (pre-dose) to time to last quantifiable concentration for ANC
  • For all primary PK/PD parameters, the 90% repeated confidence intervals of the geometric means ratio of STIMUFEND to Neulasta were entirely within the equivalence range (80%-125%), confirming bioequivalence1

Inclusion Criteria

  • Heathy males and nonpregnant females
  • Aged ≥18 to ≤55 years
  • Body mass index ≥18.0 to ≤29.9 kg/m2
  • In good health*
  • Provide signed informed consent

Exclusion Criteria

  • Signs or symptoms of COPD
  • Smoking > 10 cigarettes/day
  • Prior exposure to any CSF or growth factor 3 months (84 days) before randomization
  • Prior exposure to therapeutic mAbs targeting the bone marrow or blood cells
  • Exposure to mAbs not affecting bone marrow or blood cells was allowed before screening†
  • Blood (≥500 mL) or plasma donation within 3 months (84 days)
  • Stem cell or bone marrow donation within 12 months (336 days) before screening

Patients who were positive for anti-PEG antibodies at screening could be included in the study.1

*Based on comprehensive medical history, physical examination, vital signs, and clinical laboratory tests.
†If mAbs discontinued > 3 months (84 days) or 5 half-lives (whichever was longer).

View the clinical trial article by Lickliter, et al in Clin Ther.

Similar immunogenicity to Neulasta2

  • STIMUFEND demonstrated non-inferiority to Neulasta with confirmed immunogenicity rates of 8.9% and 9.5% respectively
  • The immunogenicity and safety profiles of STIMUFEND were demonstrated in healthy subjects in a double-blind, randomized, parallel-group, Phase I study (NCT03251339)2
  • A total of 336 subjects were randomized and treated
  • Primary endpoints were confirmed treatment-induced ADA-positive status and confirmed NAb status to pegfilgrastim from predose until the end of study
  • STIMUFEND demonstrated non-inferiority with Neulasta with confirmed immunogenicity rates of 8.9% and 9.5%, respectively2
  • No filgrastim-specific neutralizing antibodies were detected in either treatment group2

Immunogenicity with ADA rates at any time after the first dose of 2 single doses2

Chart showing immunogenicity with ADA rates

‡Upper limit of the exact one-sided adjusted 95% CI: 6.25. Confidence interval (CI) determined using Clopper-Pearson method.

Inclusion criteria2

  • Heathy males and nonpregnant females
  • Aged ≥18 to ≤55 years
  • Body mass index ≥18.0 to ≤29.9 kg/m2
  • In good health*
  • No known hypersensitivity to any component of either pegfilgrastim product
  • All subjects were required to comply with the contraception requirements specified in the clinical study protocol
  • Provide signed and dated written informed consent

Exclusion criteria2

  • Signs or symptoms of COPD
  • Smoking > 10 cigarettes/day
  • Splenomegaly (spleen size > 13 cm in the craniocaudal dimension by US)
  • Prior exposure to any CSF or growth factor 3 months (84 days) before randomization
  • Prior exposure to therapeutic mAbs targeting the bone marrow or blood cells
  • Exposure to mAbs not affecting bone marrow or blood cells allowed before screening†
  • Blood (≥500 mL) or plasma donation within 3 months (84 days)
  • Stem cell or bone marrow donation within 12 months (336 days) before screening
*Based on comprehensive medical history, physical examination, vital signs, and clinical laboratory tests.
†If mAbs discontinued > 3 months (84 days) or 5 half-lives (whichever was longer).

Highly similar safety and tolerability profile

Most common TEAEs (>5% of subjects)

TEAEs STIMUFEND
(n=270)
n (%)		 Neulasta
(n=266)
n (%)
Headache 151 (55.9) 150 (56.4)
Musculo-skeletal pain 133 (49.3) 114 (42.9)
Bone pain 67 (24.8) 70 (26.3)
Back pain 45 (16.7) 55 (20.7)
Upper respiratory tract infection 32 (11.9) 20 (7.5)
Nausea 30 (11.1) 31 (11.7)
Injection-site pain 28 (10.4) 25 (9.4)
Myalgia 27 (10.0) 23 (8.6)
Neutro-penia 24 (8.9) 22 (8.3)
Abdominal pain 23 (8.5) 21 (7.9)
Palpita-tions 23 (8.5) 14 (5.3)
Injection-site bruising 17 (6.3) 18 (6.8)
Abdominal pain upper 13 (4.8) 19 (7.1)
Leuko-cytosis 13 (4.8) 14 (5.3)
  • Adverse events with STIMUFEND were consistent with the administration of Neulasta1
  • TEAEs were generally mild to moderate in severity and were self-limiting1
  • Clinically significant splenomegaly* (Grade 1 or 2): STIMUFEND (n=3); all resolved spontaneously with no further study drug administered1
*Rare cases of splenic rupture have been reported following administration of filgrastim or pegfilgrastim; therefore, the spleen was monitored throughout the study.

Most common TEAEs (>5% of subjects)

TEAEs STIMUFEND
(n=168)
n (%)		 Neulasta
(n=168)
n (%)
Headache 105 (62.5) 120 (71.4)
Bone pain 113 (67.3) 101 (60.1)
Spinal pain 67 (39.9) 68 (40.5)
Upper respiratory tract infection 32 (19.0) 20 (11.9)
Nausea 32 (19.0) 19 (11.3)
White blood cell count increased* 23 (13.7) 27 (16.1)
Myalgia 19 (11.3) 17 (10.1)
Vomiting 18 (10.7) 9 (5.4)
Musculo-skeletal chest pain 12 (7.1) 17 (10.1)
Abdominal pain 9 (5.4) 15 (8.9)
Diarrhea 8 (4.8) 15 (8.9)
Oropharyngeal pain 12 (7.1) 14 (8.3)
Injection-site bruising 12 (7.1) 10 (6.0)
Arthralgia 11 (6.5) 11 (6.5)
Dizziness 11 (6.5) 11 (6.5)
Contusion 11 (6.5) 7 (4.2)
Fatigue 7 (4.2) 11 (6.5)
Back pain 8 (4.8) 9 (5.4)
  • TEAEs were generally mild to moderate in severity, self-limiting, and resolved without sequelae2
  • Both instances of splenomegaly (Grade 1 and 2, respectively) resolved spontaneously, and the patients completed the study2
*All events considered related to study drug.
ADA, antidrug antibody; ANC, absolute neutrophil count; AUC, area under the curve; AUE, area under the effect-time curve; Cmax, maximum concentration; COPD, chronic obstructive pulmonary disease; CSF, colony-stimulating factor; Emax, maximum observed effect; FDA, US Food and Drug Administration; mAb, monoclonal antibody; NAb, neutralizing antibody; PD, pharmacodynamic; PEG, polyethylene glycol; PK pharmacokinetic; SD, standard deviation; TEAE, treatment-emergent adverse event.

Learn How to Administer STIMUFEND

References:
  1. Lickliter J, Kanceva R, Vincent E, et al. Pharmacokinetics and pharmacodynamics of a proposed pegfilgrastim biosimilar MSB11455 versus the reference pegfilgrastim Neulasta in healthy subjects: a randomized, double-blind trial. Clin Ther. 2020;42(8):1508-1518.e1. doi:10.1016/j.clinthera.2020.05.020
  2. Wynne C, Schwabe C, Vincent E, et al. Immunogenicity and safety of a proposed pegfilgrastim biosimilar MSB11455 versus the reference pegfilgrastim Neulasta® in healthy subjects: a randomized, double-blind trial. Pharmacol Res Perspect. 2020;8(2):e00578. doi:10.1002/prp2.578