%
n
N
%
n
N
%
FTET Cycle 1a
Ongoing pregnancy
55
148
37.2
45
147
30.6
43
152
28.3
42
145
29.0
Live birth
-
-
-
-
-
-
43
152
28.3
41
145
28.3
FTET Cycle 2a
Ongoing pregnancy
9
38
23.7
9
31
29.0
8
23
34.8
6
14
42.9
Live birth
-
-
-
-
-
-
8
23
34.8
6
14
42.9
n = number of subjects with the event; N = total number of subjects
a Per embryo transfer.
Congenital malformations reported in infants born after a frozen-thawed embryo transfer (FTET) cycle
Following use of Elonva, 61 infants were born after an FTET cycle in the PURSUE study follow-up, and 607 infants were born after fresh ART cycles in the ENSURE, ENGAGE and PURSUE studies combined. The rates for congenital malformations (major and minor combined) reported for infants born after an FTET cycle in the PURSUE study follow-up (16.4%) were similar to those reported for infants born after fresh ART cycles in the ENSURE, ENGAGE and PURSUE studies combined (16.8%).
Immunogenicity
Of the 2,511 women treated with Elonva who were eva luated for the formation of post-treatment antibodies, four (0.16%) had evidence of antibody formation, including three who had been exposed once to Elonva and one who had been exposed twice to Elonva. In each case, these antibodies were non-neutralizing and did not interfere with the response to stimulation or the normal physiologic responses of the Hypothalamic-Pituitary-Ovarian (HPO) axis. Two of these four women became pregnant during the same treatment cycle in which antibodies were detected, suggesting that the presence of non-neutralizing antibodies after stimulation with Elonva is not clinically relevant.
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with Elonva in one or more subsets of the paediatric population in hypogonadotrophic hypogonadism (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Pharmacokinetic parameters of corifollitropin alfa were eva luated after subcutaneous administration in women undergoing a COS treatment cycle.
Due to the long elimination half-life, after administration of the recommended dose, serum concentrations of corifollitropin alfa are sufficient to sustain multiple follicular growth for an entire week. This justifies replacement of the first seven injections of daily (rec)FSH with a single subcutaneous injection of Elonva in COS for the development of multiple follicles and pregnancy in an ART program (see section 4.2).
Body weight is a determinant of exposure to corifollitropin alfa. Corifollitropin alfa exposure after a single subcutaneous injection is 665 hours*ng/mL (AUC, 426-1,037 hours*ng/mL1) and is similar after administration of 100 micrograms corifollitropin alfa to women with a body weight less than or equal to 60 kilograms and of 150 micrograms corifollitropin alfa to women with a body weight greater than 60 kilograms.
Absorption
After a single subcutaneous injection of Elonva, the maximum serum concentration of corifollitropin alfa is 4.24 ng/mL (2.49-7.21 ng/mL1) and is reached 44 hours (35-57 hours1) postdose. The absolute bioavailability is 58% (48-70%1).
Distributio
