Efficacy, safety, and immunogenicity of a biosimilar recombinant human follicle-stimulating hormone (Folitime®) vs. Gonal-f® in women undergoing ovarian stimulation for IVF: A randomized, multicenter, evaluator-blinded, non-inferiority study

JBRA Assist Reprod. 2021 Oct 4;25(4):524-532. doi: 10.5935/1518-0557.20210023.

Abstract

Objective: We compared the efficacy, safety, and immunogenicity of a biosimilar recombinant human follicle-stimulating hormone (Folitime®) with Gonal-f® in women undergoing ovarian stimulation for in-vitro fertilization.

Methods: This randomized (1:1), multicenter, assessor-blinded, non-inferiority, parallel-group, controlled study conducted at four infertility clinics in Argentina included infertile normogonadotropic women with ages below 39 years, with menstrual cycles of 25/35 days and a body mass index of 18-32 kg/m2 undergoing assisted reproductive technology therapy. During a 5-day fixed-dose phase, the women received 225 IU/day of Folitime® (n=49) or Gonal-f® (n=44), followed by a dose-adaptation phase up to a maximum of 450 IU/day. The non-inferiority margin for oocyte retrieval was estimated at -4 oocytes (one-sided test). Immunogenicity was investigated on days 9 and 84, following the start of treatment.

Results: The mean number of oocytes retrieved was 12.6 (SD 7.4) in the Folitime® group and 13.4 (SD 6.9) in the Gonal-f® group (per protocol analysis, 95% confidence interval = -3.82; 2.33), within the non-inferiority margin. Pregnancy rate at week 10 was 24.4% among subjects treated with Folitime® and 19.5% for subjects treated with Gonal-f®. One serious adverse drug reaction-late mild ovarian hyper stimulation syndrome and deep venous thrombosis in the left deep jugular vein-occurred in a subject treated with Folitime®. None of the subjects developed antibodies against the study drugs. There were no unexpected safety findings.

Conclusions: Folitime® is non-inferior to Gonal-f®, with no differences in the safety profile and has been approved as a biosimilar in Argentina.

Keywords: Folitime®; Gonal-f®; biosimilar; in-vitro fertilization; recombinant FSH.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biosimilar Pharmaceuticals* / adverse effects
  • Female
  • Fertilization in Vitro
  • Follicle Stimulating Hormone, Human / adverse effects
  • Humans
  • Ovulation Induction
  • Pregnancy
  • Recombinant Proteins

Substances

  • Biosimilar Pharmaceuticals
  • Follicle Stimulating Hormone, Human
  • Recombinant Proteins
  • follitropin alfa