Ferring Receives EU Approval for REKOVELLE® (follitropin delta)

A novel human recombinant follicle stimulating hormone (human rFSH)
administered using an individualised dosing regimen

SAINT-PREX, Switzerland–(BUSINESS WIRE)–Ferring Pharmaceuticals announced today that the European Commission
(EC) has granted marketing authorisation for REKOVELLE®
(follitropin delta), a human recombinant follicle stimulating hormone
(human rFSH), for use in controlled ovarian stimulation for the
development of multiple follicles in women undergoing assisted
reproductive technologies (ART), such as an in vitro fertilisation
(IVF) or intracytoplasmic sperm injection (ICSI) cycle.1

REKOVELLE® is the first rFSH to be derived from a human cell
line and is the first rFSH treatment to be administered with an
individualised dosing regimen.1-5 REKOVELLE®’s
individualised dosing regimen is based on a woman’s serum anti-Müllerian
hormone (AMH) level and her body weight. With these parameters, a
specific daily dose of REKOVELLE® is determined for each
patient from the start of the ART cycle.1-4,6,7 AMH has
surfaced as one of the most reliable biomarkers for assessing ovarian
reserve. It can help predict a woman’s ovarian response to
gonadotrophin stimulation and can also help guide the dosing of
fertility treatments.8,9 AMH will be measured by a companion
diagnostic, the Elecsys® AMH Plus immunoassay from F.
Hoffmann-La Roche Ltd (Roche).6,7

The EC approval of REKOVELLE® is based on a comprehensive
clinical data package, including results from the Phase 3 ESTHER trials (Evidence-based
Stimulation Trial with Human rFSH in Europe
and Rest of World).2-4 Results of the ESTHER-1 trial
were accepted for publication in Fertility & Sterility (article
in press and available early online). The data shows that individualised
treatment with REKOVELLE® (follitropin delta), as compared to
treatment with conventional rFSH (follitropin alfa), had similar results
for the co-primary endpoints of ongoing pregnancy rates and ongoing
implantation rates. Patients receiving REKOVELLE® also
reached the optimum oocyte yield (8–14 oocytes) more often than those
receiving conventional rFSH treatment, with fewer clinically-relevant
instances of poor and excessive ovarian response. In addition, ovarian
hyperstimulation syndrome (OHSS) and/or OHSS preventive interventions
occurred less frequently (p<0.05) in women receiving REKOVELLE® than
women receiving conventional rFSH treatment.4

“REKOVELLE®’s individualised dosing regimen offers physicians
a new method to deliver a consistent, evidence-based approach to
personalising treatment for their patients, based on AMH, a highly
predictive biomarker,” commented Professor Anders Nyboe Andersen,
Principal Investigator of the ESTHER trials. “Using validated protocols
for individualisation could help physicians facilitate the best possible
outcomes for their patients by ensuring efficacy is maintained while
also reducing complications during treatment.”

REKOVELLE® is an integral part of Ferring’s commitment to
translating the practice of personalised medicine into reproductive
health and fertility. “Ferring has a long-standing commitment to
scientific advancement in reproductive health,” said Michel Pettigrew,
President of the Executive Board and COO at Ferring Pharmaceuticals. “As
a research-driven company, we believe that by focusing on innovative and
personalised approaches, we can continue to lead the way in fertility
treatments and help women to plan their futures as mothers.”

– ENDS –

About REKOVELLE® (follitropin delta)

Follitropin delta (also known as FE 999049) is the first recombinant
follicle stimulating hormone (rFSH) derived from a human cell line
(PER.C6® cell line).1-4,5,10 It has been developed
for individualised dosing based on a woman’s serum anti-Müllerian
hormone (AMH) level, as determined by a companion diagnostic, the Elecsys®
AMH Plus immunoassay from Roche,4,6,7 and her body weight.
Follitropin delta is structurally and biochemically distinct from other
existing recombinant FSH treatments.1-4,5,10

About the ESTHER trials

The ESTHER trials (Evidence-based Stimulation Trial
with Human rFSH in Europe and Rest of World) were
randomised, assessor-blind, controlled, multicentre Phase 3 trials
involving patients in 11 countries, and over 2,000 cycles of controlled
ovarian stimulation.2-4

About Ferring Pharmaceuticals

Headquartered in Switzerland, Ferring Pharmaceuticals is a
research-driven, specialty biopharmaceutical group, active in global
markets. The company identifies, develops and markets innovative
products in the areas of reproductive health, urology, gastroenterology,
endocrinology and orthopaedics. Ferring has its own operating
subsidiaries in nearly 60 countries and markets its products in 110
countries. To learn more about Ferring or its products please 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.6,7,11-14
This fully automated Elecsys® AMH Plus immunoassay, run on
the cobas® e systems and the 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 controlled ovarian stimulation (COS) and
establishment of the individual daily dose of Ferring follitropin delta
in combination with body weight in COS for the development of multiple
follicles in women undergoing an assisted reproductive technology
programme.6,7,11-14

References

1. REKOVELLE® Summary of Product Characteristics (SmPC) –
Available upon request.

2. Nyboe Andersen A et al. Efficacy and safety of follitropin
delta in an individualised dosing regimen: A randomised, assessor-blind,
controlled phase 3 trial in IVF/ICSI patients (ESTHER-1). Human
Reproduction
2016; 31: 324

3. 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

4. Nyboe Andersen A et al. Individualized versus conventional
ovarian stimulation for in vitro fertilization: a multicenter,
randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil
Steril.
In press, available early online.
doi.org/10.1016/j.fertnstert.2016.10.033

5. Arce J-C, Nyboe Andersen A, Fernandez Sanchez 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 Dec;102(6):1633–40.

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

7. Roche Diagnostics. Elecsys® AMH (anti-Mullerian hormone):
Method sheet. 2015. https://pim-eservices.roche.com.
Last accessed Novemober 2016.

8. Nelson SM et al. Anti-Müllerian hormone-based approach to
controlled ovarian stimulation for assisted conception. Hum Reprod.
2009 Apr;24(4):867–75.

9. Fleming R, Broekmans F, Calhaz-Jorge C, et al. Can
anti-Mullerian hormone concentrations be used to determine gonadotropin
dose and treatment protocol for ovarian stimulation? Reproductive
BioMedicine Online
2013;26:431–439.

10. 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):1299–307.

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

12. 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.

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

14. 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 Sep 22;13(1):107.

Contacts

Ferring Pharmaceuticals
Lindsey Rodger
Tel. +41 (0) 58
451 40 23
lindsey.rodger@ferring.com
or
Marion
Lindsay
Tel. +41 58 301 04 15
marion.lindsay@ferring.com

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