Merck remains on track to file a New Drug Application (NDA) for corifollitropin alfa with the U.S. Food and Drug Administration (FDA) in 2013.
"Infertility is an issue many couples in the U.S. face," said Robert Boostanfar, M.D., study author, reproductive endocrinologist at HRC Fertility and clinical assistant professor at the Keck School of Medicine, Department of Obstetrics and Gynecology, University of Southern California. "If approved, corifollitropin alfa may provide clinicians with a different option for women undergoing controlled ovarian stimulation prior to IVF and ICSI.”
Study Design
In the PURSUE trial, 1,390 women in the United States, aged 35-42 years, were evaluated in a randomized, double-blind, double-dummy, active controlled, non-inferiority trial. Participants, randomized and treated at 33 IVF centers in the United States, were selected based upon inclusion criteria which included women with an indication for controlled ovarian stimulation and IVF/ICSI, who were between the ages of 35 and 42 with a body weight of = 50 kg (= 110 lbs) with a regular spontaneous menstrual cycle (cycle length 24-35 days). Key exclusion criteria included women with a recent history of/or current endocrine abnormality, history of/or current polycystic ovary syndrome, previous hyper-response or ovarian hyperstimulation syndrome (OHSS), previous low/no ovarian response to FSH/human menopausal gonadotropins (hMG), luteinizing hormone (LH) > 12.0 IU/L, and those who smoke or recently stopped smoking.
The primary efficacy endpoint assessed the vital pregnancy rate, defined as the presence of at least one fetus with heart activity at least 35 days or more after embryo transfer. The predefined non-inferiority margin was -8 percent. Secondary efficacy endpoints assessed the ongoing pregnancy rates (continued heart activity at least 10 weeks after embryo transfer, or live birth), and the number of oocytes retrieved. Other endpoints included a safety evaluation.
During the first seven days of controlled ovarian stimulation, 694 women received a single injection of 150 mcg corifollitropin alfa and 696 women were treated with seven daily injections of 300 IU rFSH. The mean age (standard deviation) for both treatment arms was 38.0 (2.2) years, and body weight (standard deviation) for the corifollitropin alfa and rFSH treatment arms were 67.8 kg (10.7) and 66.6 kg (10.8), respectively. Beginning on stimulation day 5, women in both treatment arms received daily ganirelix acetate injections (0.25 mg) (n= 692, 99.7% and n= 694, 99.7%, respectively) until the time that recombinant human chorionic gonadotropin (hCG) was administered to trigger final oocyte maturation. When required, women in both treatment arms continued treatment from stimulation day 8 onwards with daily rFSH (maximally 300 IU) until three follicles reached = 17 mm. Three days after oocyte pick-up, two good quality embryos were to be transferred.
Efficacy Results
In the corifollitropin alfa treatment arm, the vital pregnancy rate per started cycle was comparable to that achieved in the rFSH treatment arm (n=166, 23.9% vs. n= 187, 26.9%, respectively). In line with the vital pregnancy rate, the observed ongoing pregnancy rate was 22.2 percent (n=154) per started cycle in the corifollitropin alfa treatment arm and 24.0 percent (n=167) per started cycle in the rFSH treatment arm. The estimated differences and 95 percent confidence intervals were -3.0 percent [-7.4 to 1.4] for the vital pregnancy rate and -1.9 percent [-6.1 to 2.3] for the ongoing pregnancy rate. The mean (standard deviation) number of recovered mature oocytes per started cycle was 10.7 (7.2) and 10.3 (6.8), respectively, with a 95 percent confidence interval of 0.5 (-0.2 to 1.2).
Safety Profile
The overall rate of drug-related adverse events was 20.5 percent for woman receiving corifollitropin alfa and 18.5 percent for woman receiving rFSH. The overall incidence of serious adverse events (>1.0%) in the corifollitropin alfa and rFSH treatment arms were 0.4 percent versus 2.6 percent, respectively. Treatment discontinuations due to adverse events (AEs) were 0.7 percent for women receiving corifollitropin alfa versus 0.9 percent for women receiving rFSH. The drug-related incidence of ovarian hyperstimulation syndrome (OHSS) in the corifollitropin alfa and rFSH treatment arms were 1.7 percent versus 1.4 percent. The number of reported incidences of OHSS in the corifollitropin alfa and rFSH groups that required hospitalization were 0.0 percent versus 0.3 percent, reported as a SAE were 0.0 percent versus 0.7 percent, or graded II (moderate) and/or III (severe) were 0.7 percent versus 1.4 percent, respectively. The most common drug-related AEs (>1.0%) in women receiving corifollitropin alfa and rFSH, respectively, included headache (6.1% vs. 5.6%), pelvic discomfort (5.8% vs. 5.9%), nausea (3.9% vs. 2.4%), breast tenderness (2.6% vs. 1.1%), fatigue (1.9% vs. 2.0%), pelvic pain (1.6% vs. 1.6%), injection site pain (1.2% vs. 0.6%), and dizziness (0.6% vs. 1.1%).
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