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

B. C.J.M. Fauser, M. J.L. Mannaerts, P. Devroey, A. Leader, I. Boime, D. T. Baird

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

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 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. 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 μg, 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.

Original languageEnglish
Pages (from-to)309-321
Number of pages13
JournalHuman Reproduction Update
Volume15
Issue number3
DOIs
StatePublished - 2009

Keywords

  • Corifollitropin alfa
  • FSH
  • IVF
  • Ovarian stimulation

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