title: Comparison of pharmacokinetic and safety profiles between Bemfola(®) and Gonal-f(®) after subcutaneous application.
abstract: Recombinant human follicle stimulating hormone (r-hFSH) is effective and safe for controlled ovarian stimulation. Bemfola(®) (Finox AG, Burgdorf, Switzerland), a new biosimilar r-hFSH, has proven comparable non-clinical pharmacological profiles to those of the widely used Gonal-f(®) (Serono Pharma S.p.A., Bari, Italy). The objective of this study was to show that Bemfola(®) yields comparable clinical pharmacokinetic (PK) and safety profiles to Gonal-f(®) in healthy female subjects. In this randomized, Phase I trial conducted in healthy female volunteers (N = 32), a 2-period, balanced 2-treatment crossover design was used. A single subcutaneous dose of 225 IU Bemfola(®) or Gonal-f(®) was administered in each treatment period per sequence. Blood was collected for pharmacokinetic analysis until 10 days after each r-hFSH treatment. For down-regulation of endogenous FSH subjects were given a depot injection with leuprolide acetate prior to the study drug in either sequence. Pharmacokinetic data was available for 23 subjects. No appreciable differences in key PK parameters were detected between the r-hFSH products as per non-compartmental PK analysis [i.e. for Bemfola(®) and Gonal-f(®) respectively AUC0-192 424.90 and 432.75 IU h/L, C max 0.98 and 0.95 IU/L, T max 24.0 h (range 6.0-24.0) and 24.0 h (range 9.0-24.0), t 1/2 43.58 h [standard deviation (SD 14.17)] and 42.58 h (SD 16.47), and K e 0.0075 1/h (SD 0.003) and 0.0077 1/h (SD 0.002)]. Subgroup analysis for estradiol (E2) response was similar for Bemfola(®) and Gonal f(®) (AUC(0--120) p = 0.21 and C max p = 0.82). No major safety issues were identified and no immunogenic reaction to r-hFSH was observed. The results of this study indicate that a single dose of Bemfola(®) exhibits pharmacokinetic and safety profiles comparable to Gonal-f(®) in healthy young women.
authors: Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: Michael
authors: M
authors: Wolzt
authors: Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: Ghazeleh
authors: G
authors: Gouya
authors: Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: Michael
authors: M
authors: Sator
authors: Polymun Scientific Immunbiologische Forschung GmbH, Donaustrasse 99, 3400, Klosterneuburg, Austria.
authors: Thomas
authors: T
authors: Hemetsberger
authors: Finox AG, Technikumstrasse 2, 3401, Burgdorf, Switzerland. charlotte.irps@finoxbiotech.com.
authors: Charlotte
authors: C
authors: Irps
authors: Finox AG, Technikumstrasse 2, 3401, Burgdorf, Switzerland.
authors: Manfred
authors: M
authors: Rettenbacher
authors: Polymun Scientific Immunbiologische Forschung GmbH, Donaustrasse 99, 3400, Klosterneuburg, Austria.
authors: Brigitta
authors: B
authors: Vcelar
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000009:adverse effects* / Q000493:pharmacokinetics*; D006801:Humans; D016729:Leuprolide / Q000737:chemistry; D010062:Ovulation Induction / Q000379:methods; D011994:Recombinant Proteins / Q000009:adverse effects* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D059451:Biosimilar Pharmaceuticals; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C571801:follitropin alfa; D004958:Estradiol; D016729:Leuprolide
keywords: Biosimilar; Follicle-stimulating hormone; Infertility; Pharmacokinetics
references: N Engl J Med. 2009 Nov 12;361(20):1917-9
references: 19828525
references: Nat Biotechnol. 2010 Jan;28(1):28-31
references: 20062035
references: Blood. 2012 Dec 20;120(26):5111-7
references: 23093622