aration in a COS treatment cycle. The long duration of FSH activity was achieved by adding the carboxy-terminal peptide of the β-subunit of human chorionic gonadotropin (hCG) to the β-chain of human FSH. Corifollitropin alfa does not display any intrinsic LH/hCG activity.
Clinical efficacy and safety
In three randomized, double-blind, clinical trials, treatment with a single subcutaneous injection of Elonva, 100 micrograms (ENSURE study) or 150 micrograms (ENGAGE and PURSUE study), for the first seven days of COS was compared to treatment with a daily dose of 150, 200, or 300 IU of recFSH, respectively. Pituitary suppression with a GnRH antagonist (ganirelix acetate injection at a daily dose of 0.25 mg) was used in each of the three clinical trials.
In the ENSURE study, 396 healthy normal ovulatory women, aged 18 to 36 years with a body weight less than or equal to 60 kg, were treated for one cycle with 100 micrograms of Elonva and pituitary suppression with a GnRH antagonist as part of an ART program. The primary efficacy endpoint was number of oocytes retrieved. The median total duration of stimulation was 9 days for both groups, indicating that two days of recFSH were required to complete ovarian stimulation from stimulation day 8 onwards (recFSH was given on the day of hCG for this study).
In the ENGAGE Study, 1,506 healthy normal ovulatory women, aged 18 to 36 years with a body weight greater than 60 kg and less than or equal to 90 kg, were treated for one cycle with 150 micrograms of Elonva and pituitary suppression with a GnRH antagonist as part of an ART program. The co-primary efficacy endpoints were ongoing pregnancy rate and number of oocytes retrieved. The median total duration of stimulation was 9 days for both groups, indicating that two days of recFSH were required to complete ovarian stimulation from stimulation day 8 onwards (recFSH was given on the day of hCG for this study).
In the PURSUE study, 1,390 healthy normal ovulatory women, aged 35 to 42 years with a body weight greater than or equal to 50 kg, were treated for one cycle with 150 micrograms of Elonva and pituitary suppression with a GnRH antagonist as part of an ART program. The primary efficacy endpoint was vital pregnancy rate. The number of oocytes retrieved was a key secondary efficacy endpoint. The median total duration of stimulation was 9 days for both groups, indicating that one day of recFSH was required to complete ovarian stimulation from stimulation day 8 onwards (no recFSH was given on the day of hCG for this study).
Number of oocytes retrieved
In all three studies, treatment with a single injection of Elonva, 100 or 150 micrograms, for the first seven days of COS, resulted in a higher number of oocytes retrieved compared with a daily dose of recFSH. However, the differences were within the predefined equivalence (ENGAGE and ENSURE) or non-inferiority (PURSUE) margins. See Table 1 below.
Table 1: Mean Number of Oocytes Retrieved from ENSURE, ENGAGE, and PURSUE
Intent-to-Treat Population (ITT)
Parameter
ENSURE
(18-36 years of age)
(body weight less than or equal to 60 kg)
ENGAGE
(18-36 years of age)
(body weight greater than 60 kg and less than or equal to 90 kg)
PURSUE
(35-42 years of age)
(body weight greater than or equal to 50 kg)
Elonva
100 µg
recFSH
150 IU
Elonva
150 µg
recFSH
200 IU
Elonva
150 µg
recFSH
300 IU
N=268
N=128
N=756
N=750
N=694
N=696
Mean number of oocytes
13.3
10.6 |
