A global leader in developing therapeutic antibodies targeting glycosylated epitopes on cancer cells and optimizing the sugar chains (glycosylation) of biopharmaceuticals, today 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 to the standard treatment Gonal-f®. FSH-GEX™ is the first fully human glycosylated FSH (follicle-stimulating hormone), recombinantly expressed in human cells and glycooptimized to mimic endogenous human FSH.
The Phase II, multicenter, multinational, randomized 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 intra-cytoplasmic 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 to 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 to 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, while 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-GEXTM patients.
“FSH-GEX™ is the first of our glycooptimized, 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 in vitro fertilisation, 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.
About FSH and In Vitro Fertilisation
The follicle-stimulating hormone (FSH) is responsible for follicle maturation. Its main clinical use is administration during the onset of in vitro fertilization procedures to induce maturation of multiple oocytes for retrieval.
Currently, approved preparations of FSH originate from either human urine or recombinant sources from non-human cells. While urinary versions of FSH carry a heterogeneous but human glycosylation, the generally better biological safety of recombinant products makes them the product of choice for most patients, despite a non-human glycosylation profile and higher product costs associated with the treatment.
Glycotope’s glycooptimized and fully human version of FSH, FSH-GEX™, combines the advantages of both product types into one single product and adds efficacy advantages. The aim of the program was to generate a BioSuperior molecule mimicking the FSH of a healthy woman. Using GlycoExpress™, which allows for fully human glycosylation and optimization of this process, FSH-GEX™ showed an improved activity in human in vitro assays as well as in the first trials and superior production yields and reproducibility of quality by production in GlycoExpress™. It thereby provides the safety advantages of a recombinant protein with the advantages of a fully human glycosylation and an optimized glycosylation.
Glycotope, founded 2001 in Berlin, focuses on the development of innovative antibodies for the treatment of various cancer types. These GlycoBodiesTM target glycostructures or carbohydrate-peptide mixed epitopes on cell surfaces. In addition, Glycotope develops so-called BioSuperiors, antibody and non-antibody recombinant biopharmaceuticals with optimized and fully human sugar structures for clinical superiority. Key to the glycooptimization technology is a toolbox of glycoengineered proprietary human cell lines that allow the glycooptimization of proteins in respect to a whole series of different determining sugars and is based on fully human glycosylation. GlycoExpress™ allows the selection of the most appropriate and best suitable human glycoform of a product and a high yield production superior in reproducibility, quality and yield. Glycooptimization via GlycoExpress™ provides improved efficacy, bioavailability, immunogenicity and broadens the potential patient populations and indications, as well as providing a much improved cost-effectiveness.
Glycotope has currently four products in clinical development from late stage Phase I to late stage Phase II. The Company’s additional pipeline includes preclinical non-antibody and antibody biopharmaceuticals for various indications.
Together with its subsidiary, Glycotope Biotechnology in Heidelberg, Glycotope has evolved into a leading fully integrated glycobiology company, covering the entire workflow from discovery, molecule optimization, clone and process development, preclinical and clinical drug development to GMP production. With more than 160 employees and a strong, broad IP-platform, Glycotope today is one of the largest biotechnology companies in Germany.