Background/Aim: Follicle-stimulating hormone (FSH) therapy is a critical treatment for infertility. This phase 3 noninferiority study compared two recombinant human FSH (r-hFSH) prefilled pen solutions — Foligraf® (biosimilar) and Gonal-f® (innovator) — in efficacy, immunogenicity, safety, and ease of use for controlled ovarian stimulation (COS) in assisted reproductive technology (ART).

Methods: A randomized, assessor-blind, parallel-group, multicenter study was conducted at 14 centers in India and 4 in Russia (August 2022–October 2023). A total of 257 women aged 20–39 years with infertility requiring COS for ART, BMI 18–30 kg/m², and normal ovarian reserve (AFC ≥10; AMH 1.0–3.5 ng/mL) were randomized 1:1 to Foligraf® or Gonal-f®. Both groups received 225 IU/day r-hFSH subcutaneously from cycle day 2/3, adjusted based on ovarian response (maximum 450 IU/day). The primary endpoint was number of oocytes retrieved (noninferiority margin: ±2.9 oocytes). Secondary endpoints included clinical and ongoing pregnancy rates, embryo quality, total r-hFSH dose, and stimulation duration.

Results: Of 257 enrolled subjects, 252 comprised the modified ITT population (Foligraf®: 125; Gonal-f®: 127). The least squares mean oocytes retrieved was 8.83 (±0.46) for Foligraf® vs 8.89 (±0.46) for Gonal-f® [90% CI: −0.06 (−1.34 to 1.21); p = 0.9247], confirming noninferiority. Mature (stage III) oocytes comprised 75.3% vs 71.0%. Clinical pregnancy rate was 20.00% vs 22.05% (p = 0.6765), and ongoing pregnancy rate was 17.60% vs 19.69% (p = 0.9294). Total r-hFSH dose (2551 vs 2457 IU; p = 0.5703), stimulation duration (11.2 vs 10.8 days; p = 0.2935), and embryo quality were comparable. 

Adverse events were predominantly mild; OHSS occurred in 3 subjects (1.17%). Anti-r-hFSH antibody positivity was low and comparable, with no clinically meaningful immunogenicity difference.

Conclusion: Foligraf® prefilled pen demonstrated noninferiority to Gonal-f® in efficacy and was comparable in safety and immunogenicity, supporting its use as an effective, well-tolerated biosimilar r-hFSH option for COS in ART.

Pratik Shah, MD, MSc, is Senior Vice President and Head of Medical Affairs at Bharat Serums and Vaccines Limited (BSV), a leading biopharmaceutical company focused on vaccines and biologics. With over 18 years of experience in pharmaceuticals , he specializes in clinical development, regulatory strategy, pharmacovigilance, and medical affairs, particularly in nephrology, neurology, oncology, and organ transplants. His leadership has advanced clinical pipelines, global trials, and cross-functional teams, earning the Astellas CEO Award (2014) and STAR Employee of the Year (2011). Prior roles include Vice President of Medical Affairs at BSV (2020–2025), CEO of PrimeRx Solutions Pvt Ltd (2018–2025), and senior positions at Astellas Pharma, such as Head of Clinical Research & Development (2009–2018), where he established departments, SOPs, and expanded portfolios. He also served as therapeutic area consultant at Johnson & Johnson (2009) and clinical study manager at Sanofi-Aventis (2006–2008), overseeing phase III/IV trials and budgets. Holding an MD in Pharmacology (Nair Hospital), MSc in Pharmaceutical Medicine (Hibernia College), PGDCR (ICRI), PGDPM (K.C. College), and SPJIMR certification, he is an OPPI member driving innovation in drug development and medical education.