Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency.
BACKGROUND
Recombinant DNA technologies have been used to develop longer-acting therapeutic proteins. One approach is to introduce sequences containing additional glycosylation sites. Using this technique, a new chimeric gene has been developed containing the coding sequences of the FSH beta-subunit and the C-terminal peptide of the hCG beta-subunit, which bears four O-linked oligosaccharide binding sites. Co-expression of the alpha-subunit and the chimeric FSH beta-subunit produces a new recombinant molecule, named corifollitropin alfa, with a prolonged elimination half-life and enhanced in vivo bioactivity compared with wild-type FSH.


METHODS
Medline searches by subject and additional searching by hand.


RESULTS
Initial studies in pituitary suppressed female volunteers confirmed the extended half-life of the compound. Phase II studies have shown that corifollitropin alfa is able to induce and sustain multi-follicular growth for an entire week in women undergoing ovarian stimulation using GnRH antagonist co-treatment for IVF. Corifollitropin alfa regimens have been developed with dosages of 100 and 150 microg, for patients with body weight </=60 and >60 kg, respectively.


CONCLUSIONS
Corifollitropin alfa is the first long-acting hybrid molecule with sustained follicle-stimulating activity developed for the induction of multi-follicular growth along with GnRH antagonist co-treatment for IVF. This new treatment option may be simpler and more convenient for patients compared with conventional long protocols of daily FSH injections in combination with GnRH agonist co-treatment. The safety and efficacy of such regimens is currently being evaluated in large comparative phase III clinical trials. The development of corifollitropin alfa is the first step towards a new generation of recombinant gonadotrophins.
Fauser
B C J M
BC
Department of Reproductive Medicine and Gynecology, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. b.c.fauser@umcutrecht.nl
Mannaerts
B M J L
BM
Devroey
P
P
Leader
A
A
Boime
I
I
Baird
D T
DT
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004274:DNA, Recombinant / Q000737:chemistry*; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development; D010062:Ovulation Induction / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*
D004274:DNA, Recombinant; D043373:Follicle Stimulating Hormone, Human; D011993:Recombinant Fusion Proteins; C437186:follicle stimulating hormone, human, with HCG C-terminal peptide; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone