Pharmacological profile, clinical efficacy, and safety of Follitropin Delta produced by recombinant DNA technology in a human cell line (REKOVELLE<sup>®</sup> PEN for S.C. Injection 12 μg, 36 μg, 72 μg)

Abstract

Follitropin Delta (Rekovellle Subcutaneous Injection 12 μg/ 36 μg/72 μg Pen) is a recombinant human follicle-stimulating hormone (rFSH) developed by Ferring Pharmaceuticals Co., Ltd. Because human follicle-stimulating hormone (FSH) gene is incorporated into a human-derived cell line (human embryonic retinoblastoma: PER.C6), the Follitropin Delta is produced with having α2.3 and α2.6 linked sialic acid sugar chain which is similar to natural human FSH. Containing these two types of sialic acids linkage, similar blood dynamics with natural FSH can be expected due to the reduction of hepatic clearance. Furthermore, an individual dose algorithm defined by patient blood anti-Müllerian hormone (AMH) level and body weight can be expected to obtain optimal follicle development and reduce the safety risk. In the phase II studies, efficacy and safety of Follitropin Delta are confirmed in a dose-dependent manner, and it is confirmed the individualized dose algorism for non-Japanese is also applicable for Japanese women by the population pharmacokinetic/pharmacodynamic analysis. In the phase III studies the non-inferiority of Follitropin Delta to Follitropin Alfa or Beta is confirmed in ongoing pregnancy rate and the number of oocytes retrievable. In addition, the number of subjects who developed total ovarian hyperstimulation syndrome and/or who underwent prophylactic intervention in the Follitropin Delta was significantly lower than comparators. In conclusion, the clinical benefits of individualized doses of Follitropin Delta were confirmed in infertile women undergoing controlled ovarian stimulation (COS) in assisted reproductive technology (ART), and we propose that Follitropin Delta may provide new options to patients and real clinical settings.