Are QL1012 and Gonal-f® equivalent in women undergoing ovarian stimulation for assisted reproductive technology (ART)?
This multicentre, randomized, assessor-blinded, phase-three trial was conducted at 13 centres in China. Eligible patients were infertile women; age 20–39 years; body mass index 18–30 kg/m2; regular menstrual cycles; and indication for ART. After successful pituitary downregulation, patients were randomly assigned (1:1) to receive QL1012 or Gonal-f®, stratified by age (initial dose of 75–150 IU for women younger than 30 years, 150–225 IU for women aged 30–34 years and 225–300 IU for women aged ≥35 years, subcutaneously, once daily). The primary end point was the number of oocytes retrieved.
Between October 2018, and June 2019, 341 patients were included in the per-protocol set. The mean numbers of oocytes retrieved were 14.7 ± 7.0 in the QL1012 group (n = 169) and 13.4 ± 6.1 in the Gonal-f® group (n = 172). Adjusted by analysis of covariance model, the least-squares mean difference was 1.3 oocytes (95% CI –0.1 to 2.7; P = 0.0650), within the pre-defined equivalence margins of ±3.0. Similar results were observed in the full analysis set. Additionally, no statistical differences were found in secondary end points except oestradiol concentration (median 3948.0 pg/ml versus 3545.3 pg/ml; P = 0.0015). Ovarian hyperstimulation syndrome (12.4% versus 13.1 %) and other adverse events were similar between the two groups.
Therapeutic equivalence and similar safety profiles were demonstrated between QL1012 and Gonal-f® in women undergoing ovarian stimulation for ART.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Reproductive BioMedicine Online
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- A multicenter, randomized, phase III study comparing the efficacy and safety of follitropin alpha biosimilar and the original follitropin alpha.Eur. J. Obstet. Gynecol. Reprod. Biol. 2019; 241: 6-12
- 'Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques'.Hum. Reprod. 1997; 12: 2133-2139
- Diagnosis and Management of Infertility: A Review.JAMA. 2021; 326: 65-76
- Competition in the Age of Biosimilars.JAMA. 2015; 314: 225-226
- Effects of the Zishen Yutai Pill Compared With Placebo on Live Births Among Women in a Fresh Embryo Transfer Cycle: A Randomized Controlled Trial.Obstetrics and Gynecology. 2022; 139: 192-201
- Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant human follicle stimulating hormone (r-hFSH).European Medicines Agency, London, UK2011
- Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review.Human Reproduction Update. 2002; 8: 559-577
- Recombinant follicle stimulating hormone: development of the first biotechnology product for the treatment of infertility.Hum. Reprod. Update. 1998; 4: 862-881
- Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics.Physiological reviews. 2016; 96: 873-909
- Recombinant human follicle-stimulating hormone: a scientific step to clinical improvement.Reprod. Biomed. Online. 2001; 2: 54-64
- Association of estradiol levels on the day of hCG administration and pregnancy achievement in IVF: a systematic review.Hum. Reprod. 2004; 19: 2446-2453
- Does the estradiol level on the day of human chorionic gonadotrophin administration have an impact on pregnancy rates in patients treated with rec-FSH/GnRH antagonist?.Hum. Reprod. 2009; 24: 2902-2909
- Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation.J. Endocrinol. Invest. 2015; 38: 497-503
- [The effect of serum estradiol levels on the outcome of controlled ovarian hyperstimulation and pregnancy].Chinese Journal of Birth Health & Heredity. 2013; 21 (+51): 139-140
- Controlled ovarian hyperstimulation: are we monitoring the appropriate sex-steroid hormones?.Fertil. Steril. 2008; 89: 1269-1272
- Percentile curves of serum estradiol levels during controlled ovarian stimulation in 905 cycles stimulated with recombinant FSH show that high estradiol is not detrimental to IVF outcome.Hum. Reprod. 2002; 17: 2846-2850
- Gonadotropin-releasing hormone antagonist use is associated with increased pregnancy rates in ovulation induction-intrauterine insemination to in vitro fertilization conversions, independent of age and estradiol level on the day of human chorionic gonadotropin administration.Fertil. Steril. 2010; 93: 605-608
- Value of the serum estradiol level on the day of human chorionic gonadotropin injection and on the day after in predicting the outcome in natural in vitro fertilization/intracytoplasmic sperm injection cycles.Fertil. Steril. 2001; 75: 539-543
- A multi-centre phase 3 study comparing efficacy and safety of Bemfola(®) versus Gonal-f(®) in women undergoing ovarian stimulation for IVF.Reproductive Biomedicine Online. 2015; 30: 504-513
- Biosimilar recombinant follicle stimulating hormones in infertility treatment.Expert Opin. Biol. Ther. 2014; 14: 1399-1409
- Randomized, active-controlled, comparative phase 3 efficacy and safety equivalence trial of Ovaleap(R) (recombinant human follicle-stimulating hormone) in infertile women using assisted reproduction technology (ART).Reprod. Biol. Endocrinol. 2016; 14: 1
- Fertility and infertility: Definition and epidemiology.Clin. Biochem. 2018; 62: 2-10
- Human menopausal gonadotropin versus recombinant follicle-stimulating hormone in normogonadotropic women down-regulated with a gonadotropin-releasing hormone agonist who were undergoing in vitro fertilization and intracytoplasmic sperm injection: a prospective randomized study.Fertil. Steril. 2001; 76: 543-549
- Epidemiology of infertility in China: a population-based study.BJOG. 2018; 125: 432-441
Professor Yingpu Sun is Chief Physician of the Reproductive Medicine Center at First Affiliated Hospital of Zhengzhou University. As a specialist in reproductive medicine, she has successively completed multiple national first cases using advanced assisted reproductive technology.
Published online: October 16, 2022
Accepted: October 12, 2022
Received in revised form: September 20, 2022
Received: April 28, 2022Declaration: Jie Wang and Fang Ma are employees of Qilu Pharmaceutical Co., Ltd.
© 2022 Published by Elsevier Ltd on behalf of Reproductive Healthcare Ltd.