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Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency

2009; Oxford University Press; Volume: 15; Issue: 3 Linguagem: Inglês

10.1093/humupd/dmn065

1460-2369

B. C. J. M. Fauser, Bernadette Mannaerts, Paul Devroey, Arthur Leader, Irving Boime, David T. Baird,

Reproductive System and Pregnancy

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 β-subunit and the C-terminal peptide of the hCG β-subunit, which bears four O-linked oligosaccharide binding sites. Co-expression of the α-subunit and the chimeric FSH β-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. Medline searches by subject and additional searching by hand. 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 µg, for patients with body weight ≤60 and >60 kg, respectively. 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.