RELEUKO® (filgrastim-ayow) injection is biosimilar to Neupogen® (filgrastim) and made entirely in the United States.1
Filgrastim is a recombinant granulocyte colony stimulating factor (rG-CSF). It promotes neutrophil production in appropriate patients.
RELEUKO® is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim products or pegfilgrastim products.
RELEUKO® clinical comparability includes data from 112 subjects evaluated in 2 PK/PD studies and 134 subjects in 1 immunogenicity/safety study:
1. Strong comparability PK package in HV clinical trials: The PK similarity of both products was established.
2. Strong Comparability PD package in HV clinical trials: As a surrogate for clinical efficacy, PD similarity of both products was established.
RELEUKO® is a biosimilar filgrastim which has been developed with Neupogen® as the Reference Product (RP).
Multiple state-of-the-art analytical methods were applied to evaluate all quality attributes required of the biosimilar and confirmed analytical similarity between RELEUKO® and Neupogen®:
Primary Structure
The same amino acid sequence is confirmed in RELEUKO® and Neupogen®.
In the figure below, the same set of twelve (12) primary peptides G1 to G12 are seen from the digestion of RELEUKO® or Neupogen® by Glu-C for peptide mapping, confirming that the primary structure of RELEUKO® and Neupogen® is the same.
Molecular Conformation
Similarity between RELEUKO® and Neupogen® in terms of molecular conformation was demonstrated as seen by identical Far-UV CD Spectra, and Intrinsic Fluorescence spectra.
Charge Variants
Cation-exchange analysis demonstrated that RELEUKO® and Neupogen® have similar content of acidic and basic forms.
Protein Content and Purity
Similar protein content and high purity was found in both RELEUKO® and Neupogen®.
Comparative Stability
Comparative accelerated and forced degradation studies have shown a similar behavior and degradation profile of RELEUKO® and Neupogen®.
The two PK/PD studies provided the comparative PD characteristics that established PD similarity and hence comparative clinical efficacy for RELEUKO® versus Neupogen®.
Over 300 subjects have been exposed to RELEUKO® along with Neupogen® in the three studies conducted as part of overall biosimilarity assessment. The safety profiles of RELEUKO® and Neupogen® appear to be safe and equally tolerated in the healthy adult subjects who were exposed to single SC doses (2.5μg/kg or 5μg kg) or multiple SC doses (5μg/kg) in the three completed clinical pharmacology and safety studies.1
Based on the two PK/PD studies and one immunogenicity study:1,2
Multiple subcutaneous administrations of RELEUKO® and Neupogen® were generally safe and similarly tolerated in the healthy adult subjects.
| System Organ Class Preferred Term | Filgrastim (N=294) | Placebo (N=157) |
|---|---|---|
| Blood & lymphatic system disorders | ||
| Thrombocytopenia | 38% | 29% |
| Gastrointestinal disorders | ||
| Nausea | 43% | 32% |
| General disorders & administration site conditions | ||
| Pyrexia | 48% | 29% |
| Chest pain | 13% | 6% |
| Pain | 12% | 6% |
| Fatigue | 20% | 10% |
| Musculoskeletal & connective tissue disorders | ||
| Back pain | 15% | 8% |
| Arthralgia | 9% | 2% |
| Bone pain | 11% | 6% |
| Pain in extremity* | 7% | 3% |
| Nervous system disorders | ||
| Dizziness | 14% | 3% |
| Respiratory, thoracic & mediatinal disorders | ||
| Cough | 14% | 8% |
| Dyspnea | 13% | 8% |
| Skin & subcutaneous tissue disorders | ||
| Rash | 14% | 5% |
| Investigations | ||
| Blood lactate dehydrogenase increased | 6% | 1% |
| Blood alkaline phosphatase increased | 6% | 1% |
| *Percent difference (Filgrastim – Placebo) was 4% | ||
Two PK/PD studies were carried out in healthy volunteers to investigate and compare the PK profiles of RELEUKO® and Neupogen® and confirmed bioequivalence between both products.
The PK results for one study are shown below. The peak and overall baseline-corrected blood ANC (as measured by geometric mean Emax and AUC0-t) were similar following a subcutaneous injection of either RELEUKO® or Neupogen®, as shown by the less than 10% difference in Emax and AUC0-t between treatments.
