Glycotope's Fully Human and Glyco-Optimized Recombinant FSH-GEX Showed Superior Activity and Excellent Tolerability in a Phase II Clinical Trial for IVF

Glycotope GmbH, a global leader in developing therapeutic antibodies targeting glycosylated epitopes on cancer cells and optimising the sugar chains (glycosylation) of biopharmaceuticals, has announced results from the Phase II clinical trial with FSH-GEX for Assisted Reproductive Technologies.

Results showed that FSH-GEX has superior activity and excellent tolerability when compared with the standard treatment Gonal-f. FSH-GEX is the first fully human glycosylated FSH (follicle-stimulating hormone), recombinantly expressed in human cells and glyco-optimized to mimic endogenous human FSH.

The Phase II, multicenter, multinational, randomised clinical trial investigated the efficacy and safety of varying doses and schedules of FSH-GEX in comparison with daily 150 IU Gonal-f in 247 women undergoing artificial insemination by intracytoplasmic sperm injection (ICSI) treatment in an agonist protocol. FSH-GEX was tested in five dose cohorts, 52.5 IU, 75 IU, 112.5 IU and 150 IU daily doses, and 150 IU given every second day, compared with the standard daily dose of 150 IU Gonal-f.

The data show that FSH-GEX, even at half the biologic dose (75 IU FSH-GEX), is at least as active as Gonal-f (150 IU) in all FSH mediated parameters and endpoints. These data confirm the superior preclinical, Phase Ia and Ib data regarding biological activity and clinical efficacy.

For example, the FSH-GEX dose of 112.5 IU, showed superiority over all FSH mediated aspects and endpoints compared with a 33% higher Gonal-f standard dose including follicular response, as well as high biochemical (57.5%) and ongoing (50.0%) pregnancy rates. Particularly important for future clinical use are the statistically significantly improved numbers of retrieved oocyte complexes (+29.5%) and high quality metaphase II oocytes (+24.5%), as well as a strong trend for more pronuclear (PN) 2 oocytes (+21%) which could be observed in this dose regimen.

Furthermore, the results at a dose regimen with 150 IU FSH-GEX applied every second day and 75 IU FSH-GEX administered on a daily basis were fully comparable, allowing for a flexible or alternative dosing regimen with the same product.

The treatment with FSH-GEX was safe and very well tolerated, whereas Gonal-f showed the highest rate of OHSS (Ovarian hyperstimulation syndrome) during the trial. No inductions of anti drug antibody (ADA) responses were observed in FSH-GEX patients.

"FSH-GEX is the first of our glyco-optimized, fully human non-antibody molecules validating our unique GlycoExpress platform and proving our commitment to delivering better, clinically superior therapies combined with commercially attractive terms," said Dr Steffen Goletz, CEO, CSO and Founder of Glycotope.

"The superior activity and improved properties of FSH-GEX, which allows for lower FSH doses and the significantly improved numbers of high quality mature oocytes that can be achieved for IVF, are seen as a key driver for best clinical performances. These results strongly indicate not only a high relevance of FSH-GEX in the tested broad patient cohort, but also yield hope for women whose ovaries are particularly hard to stimulate and who are experiencing major difficulties in becoming pregnant. We are excited about these results and anticipate starting Phase III clinical trials in 2014," he added.