Ferring Announces New Analysis of Rekovelle® Data Relating to Personalised Medicine in Fertility Patients

Ferring Pharmaceuticals announced today a new analysis of Rekovelle^® (follitropin delta) data that showed cumulative live birth rates were similar between women receiving Rekovelle and conventional follitropin alfa treatment.¹ In addition, Rekovelle data from a separate new analysis showed a favourable safety profile in women with high anti-Müllerian hormone (AMH) levels.² These analyses of the ESTHER-1 and ESTHER-2 Phase III clinical trials^3,4 were presented today at the 33^rd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Geneva, Switzerland.

“Rekovelle’s individualised dosing regimen, based on a patient’s AMH level and body weight, provides clinicians with a consistent, evidence-based approach to personalising treatment for their patients,” said Per Falk, Executive Vice President and Chief Scientific Officer, Ferring Pharmaceuticals. “These new Rekovelle analyses add further evidence for a personalised approach to fertility treatment for patients.”

A new analysis of the ESTHER-1 and ESTHER-2 trials showed that in women undergoing in vitro fertilisation (IVF), the cumulative live birth rate for fresh embryo transfers after three treatment cycles was 43.9% (292/665) with Rekovelle and 44.5% (294/661) with follitropin alfa.¹ In addition, ongoing pregnancy rate was 45.1% (300/665) and 45.7% (302/661), respectively.¹ The ESTHER trials^3,4 were not powered for this analysis, so no confirmatory conclusions can be derived.

A separate new analysis of the ESTHER-1 trial was conducted to evaluate ongoing pregnancy rates, early ovarian hyperstimulation syndrome (OHSS) and preventive interventions for early OHSS in women with different AMH levels.² For women with high AMH ≥35 pmol/L (13% of the trial population) the incidence of early OHSS with Rekovelle was lower (4.7%, 4/86) compared with conventional follitropin alfa dosing (11.9%, 10/84). The number of patients requiring preventive interventions for early OHSS was also lower (4.7%, 4/86 and 23.8%, 20/84 respectively). In addition, patients maintained ongoing pregnancy rate.² The ESTHER trials^3,4 were not powered for this analysis, so no confirmatory conclusions can be derived.

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About Rekovelle ^® (follitropin delta)
Rekovelle is the first recombinant follicle stimulating hormone (rFSH) derived from a human cell line (PER.C6^® cell line).^3,5,6,7 It has been developed for individualised dosing based on a patient’s body weight and serum AMH level, as determined by a companion diagnostic, the Elecsys^® AMH Plus immunoassay from Roche.^3,8,9 Rekovelle is structurally and biochemically distinct from other existing recombinant FSH treatments.^3,5,6,7

Rekovelle^® received Marketing Authorisation from the European Commission (EC) in December 2016.

About the ESTHER trials
ESTHER-1 (Evidence-based Stimulation Trial with Human recombinant FSH in Europe and Rest of World) is a Phase 3, randomised, assessor-blind, controlled trial of 1326 patients in 11 countries undergoing their first ART cycle. Patients were randomized 1:1 to receive treatment with individualised Rekovelle, a fixed daily dose based on serum anti-Müllerian hormone (AMH) levels and body weight, or conventional follitropin alfa dosing. The co-primary endpoints of ongoing pregnancy rates and ongoing implantation rates were met and results showed no difference between the two treatment arms. Results of the ESTHER-1 trial were published in the February 2017 issue of Fertility & Sterility.³

ESTHER-2 is a Phase 3, assessor-blind, controlled trial evaluating the immunogenicity of Rekovelle in a subset of ESTHER-1 patients undergoing repeated cycles of controlled ovarian stimulation for ART. Data demonstrated no increased immunogenicity risk with Rekovelle after exposure in repeated cycles.⁴

About AMH and OHSS
AMH is a biomarker used to assess ovarian reserve and can help predict ovarian response.¹⁰ Women with high AMH levels are at an increased risk of developing OHSS, a potential complication of IVF treatment.^11,12 Symptoms of early OHSS may include abdominal distension or discomfort, nausea and vomiting. In more severe cases OHSS can lead to large amounts of ascites (fluid accumulation in the abdominal cavity), shortness of breath, blood clots, dehydration and potentially, death.¹¹

The prevalence of OHSS in women undergoing IVF varies according to severity, with cases of OHSS experienced by 20–33% (mild), 3–6% (moderate) and 0.1–2% (severe) of women.¹³ A recent report suggested that OHSS is an underreported side effect of ovarian stimulation and the real world incidence may be higher.¹⁴ In addition to the impact on patients, the treatment of OHSS is associated with significant costs to the healthcare system.¹⁵ In the UK for example, the cost of treating moderate and severe cases of OHSS is estimated to be over £7 million every year.^15,16

About Ferring Pharmaceuticals
Headquartered in Saint-Prex, Switzerland, Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group active in global markets. A leader in reproductive and maternal health, Ferring has been developing treatments for mothers and babies for over 50 years. Today, over one third of the company’s research and development investment goes towards finding innovative treatments to help mothers and babies, from conception to birth. The company also identifies, develops and markets innovative products in the areas of urology, gastroenterology, endocrinology and orthopaedics. Ferring has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries. For further information on Ferring or its products, visit www.ferring.com.

About the Elecsys ^® AMH Plus immunoassay from Roche
The Elecsys^® AMH Plus immunoassay from Roche has been shown to provide a precise, reliable and robust measurement of AMH levels.^{8,9,17,18,19,20} This fully automated Elecsys^® AMH Plus immunoassay, run on the cobas ^® e and Elecsys^® immunoassay analysers, determines AMH levels in 18 minutes, making it appropriate for routine clinical use. The Elecsys^® AMH Plus immunoassay is intended to be used for assessment of ovarian reserve, prediction of response to COS and establishment of the individual daily dose of Rekovelle in combination with body weight in COS for the development of multiple follicles in women undergoing an assisted reproductive technology programme.^{8,9,17,18,19,20}

References

¹ Havelock J, Bosch E, Sanchez F, et al. Cumulative ongoing pregnancy and live birth rates following repeated controlled ovarian stimulation (COS) cycles using individualised follitropin delta dosing compared to conventional follitropin alfa dosing [abstract] In: 33rd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE); 2017; Geneva, Switzerland. Abstract no. 0-168

² La Marca A, Nelson S, Gothberg M, et al. The impact of serum anti-Müllerian hormone (AMH) levels on clinical outcome of individualized follitropin delta dosing and conventional follitropin alfa dosing in controlled ovarian stimulation [abstract]. In: 33rd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE); 2017; Geneva, Switzerland. Abstract no. 0-174

³ Nyboe Andersen A, Nelson SM, Fauser BC, et al. Individualised versus conventional ovarian stimulation for an in vitro fertilization: a multicenter, randomized, controlled assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2017: 107(2): 387-396

⁴ Buur Rasmussen A et al. Low immunogenicity potential of follitropin delta, a recombinant FSH preparation produced from a human cell line: Results from phase 3 trials (ESTHER-1 and ESTHER-2). Human Reproduction 2016; 31: 385

⁵ Rekovelle^® Summary of Product Characteristics (SmPC) – Available at: https://www.medicines.org.uk/emc/medicine/33324 [Last accessed: June 2017]

⁶ Arce JC, Andersen AN, Fernández-Sánchez M, et al. Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimullerian hormone–stratified, dose–response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2014;102(6):1633–1640

⁷ Olsson H, Sandström R, Grundemar L. Different pharmacokinetic and pharmacodynamic properties of recombinant follicle-stimulating hormone (rFSH) derived from a human cell line compared with rFSH from a non-human cell line. J Clin Pharmacol. 2014; 54(11):1299–1307

⁸ Deeks ED. Elecsys^® AMH assay: a review in anti-Müllerian hormone quantification and assessment of ovarian reserve. Mol Diagn Ther. 2015; 19: 245-249

⁹ Roche Diagnostics. Elecsys^® AMH (anti-Mullerian hormone): Method sheet. 2015. https://pim-eservices.roche.com. [Last accessed June 2017]

¹⁰ La Marca A, Sighinolfi G, Radi D, et al. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010; 16(2):113-130

¹¹ OHSS Symptoms and Causes. Patient Care and Health Information. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/ovarian-hyperstimulation-syndrome-ohss/symptoms-causes/dxc-20263586 [Last accessed: June 2017]

¹² Salmassi A, Mettler L, et al. Cut-Off Levels of Anti-Mullerian Hormone for the Prediction of Ovarian Response, In Vitro Fertilization Outcome and Ovarian Hyperstimulation Syndrome. Int J Fertil Steril. 2015; 9(2): 157-167

¹³ Delvigne A, Rozenberg S, et al. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002; 8(6): 559-577

¹⁴ Thomsen L, Humaidan P, et al. Ovarian hyperstimulation syndrome in the 21^st century: the role of gonadotropin-releasing hormone agonist trigger and kisspeptin. Curr Opin Obstet Gynecol. 2015; 27(3): 210-214

¹⁵ Yates AP, Rustamov O, Roberts SA, et al. Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF. Hum Reprod. 2011; 26(9): 2353-2362

¹⁶ Fertility Treatment in 2014 Trends and Figures Report. Human Fertilisation and Embryology Authority. http://www.hfea.gov.uk/docs/HFEA_Fertility_treatment_Trends_and_figures_2014.pdf [Last accessed June 2017]

¹⁷ Gassner D, Jung R. First fully automated immunoassay for anti-Müllerian hormone. Clin Chem Lab Med. 2014;52(8):1143-1152

¹⁸ Anderson RA, Anckaert E, Bosch E, et al. Prospective study into the value of the automated Elecsys antimüllerian hormone assay for the assessment of the ovarian growing follicle pool. Fertil Steril. 2015;103(4):1074–80.e4

¹⁹ Nelson SM, Pastuszek E, Kloss G, et al. Two new automated, compared with two enzyme-linked immunosorbent antimüllerian hormone assays. Fertil Steril. 2015;104(4):1016-1021.e6

²⁰ Hyldgaard J, Bor P, Ingerslev HJ, et al. Comparison of two different methods for measuring anti-mullerian hormone in a clinical series. Reprod Biol Endocrinol. 2015;13(1):107

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Contact information

Ferring Pharmaceuticals
Lindsey Rodger
Corporate Communications Manager
+41 58 451 40 23 (direct)
+41 79 191 0486 (mobile)
lindsey.rodger@ferring.com
or
Bhavin Vaid
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+41 79 191 06 32 (mobile)
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