Ferring receives positive CHMP opinion for REKOVELLE® (follitropin delta)

Guía de Regalos

If approved, Ferring’s novel human recombinant follicle stimulating
hormone (FSH) would be administered using an individualised dosing
regimen

SAINT-PREX, Switzerland–(BUSINESS WIRE)–Ferring Pharmaceuticals announced today that the Committee for Medicinal
Products for Human Use (CHMP) has adopted a positive opinion for
REKOVELLE® (follitropin delta), recommending that the
European Commission grants marketing authorisation 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.1-3 The European Commission has authority to grant
marketing authorisation for medicines in the 28 countries of the
European Union (EU). Following a European Commission decision,
authorisation can also be granted by national authorities in Norway and
Iceland.

If approved, REKOVELLE® would be administered using an
individualised dosing regimen according to a woman’s serum
anti-Müllerian hormone (AMH) level and her body weight. AMH is a
biomarker used to assess ovarian reserve.4,5 This can help to
predict ovarian response to controlled ovarian stimulation and thus
identify patients who may be at higher risk of experiencing reduced
efficacy or increased safety concerns.4,6,7 The
individualised dosing regimen determines a specific daily dose of
REKOVELLE® for each patient, with the aim of maintaining
efficacy and improving safety during controlled ovarian stimulation. AMH
would be measured by a companion diagnostic, the Elecsys® AMH
Plus immunoassay from F. Hoffmann-La Roche Ltd (Roche).8,9

“The individualised dosing regimen for REKOVELLE® aims to
further enrich the personalised care that fertility specialists offer
their patients,” said Dr Per Falk, M.D. Ph.D., Chief Scientific Officer
and Executive Vice President at Ferring Pharmaceuticals. “If approved,
this would be the first pairing of a drug with a companion diagnostic
for individualised dosing in reproductive medicine.”

The CHMP positive opinion is based on a comprehensive clinical
development programme, including the Phase 3 ESTHER trials
(Evidence-based Stimulation Trial with Human recombinant FSH in Europe
and Rest of World), involving 1,326 patients in 11 countries, and over
2,000 cycles of controlled ovarian stimulation.1-3,10,11

Non-inferiority was demonstrated in a Phase 3 trial for the co-primary
endpoints of ongoing pregnancy rate and ongoing implantation rate for
REKOVELLE® compared to follitropin alfa (conventional
treatment and dosing regimen). Secondary endpoints, including the number
of oocytes retrieved and number of blastocysts obtained, were comparable
between both groups. The Phase 3 clinical trials also demonstrated no
increased immunogenicity risk and a good safety profile for REKOVELLE®
with repeated cycles of controlled ovarian stimulation.3,11

About REKOVELLE® (follitropin delta)

Follitropin delta (also known as FE 999049) is the first recombinant
follicle stimulating hormone (FSH) derived from a human cell line.1,12
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,1,5,6,8,9
and her body weight. Follitropin delta is structurally and clinically
distinct from other existing recombinant FSH treatments.1,12

About the ESTHER trials

The ESTHER trials (Evidence-based Stimulation Trial
with Human recombinant FSH in Europe and Rest of
World) were randomised, assessor-blind, controlled, multicentre Phase 3
trials involving fertility clinics in Europe, Canada, Brazil and Russia.2,3

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.8,9,13-16
This fully automated Elecsys® AMH Plus immunoassay uses 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 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 program.8,9,13-16

References

1. 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.

2. ESTHER-1 trial. www.clintrials.gov
Available at: https://clinicaltrials.gov/ct2/show/NCT01956110.
Last accessed: September 2016.

3. ESTHER-2 trial. www.clintrials.gov.
Available at: https://clinicaltrials.gov/ct2/show/NCT01956123.
Last accessed: September 2016

4. 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.

5. La Marca A and Sunkara SK. Individualization of controlled ovarian
stimulation in IVF using ovarian reserve markers: from theory to
practice. Hum Reprod Update 2014;20: 124–140.

6. American Society for Reproductive Medicine. Medications for Inducing
Ovulation – A guide for patients. Available at: http://www.asrm.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/ovulation_drugs.pdf.
Last accessed: September 2016.

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

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 Plus: Method sheet. 2016.

10. Nyboe Andersen A and Arce JC on behalf of the ESTHER-1 trial group.
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). Poster presented at 32nd Annual Meeting of
the European Society of Human Reproduction and Embryology (ESHRE) in
Helsinki, 3–6 July 2016. Hum Reprod. 2016;31(Supp 1):i315.

11. Buur Rasmussen A et al, on behalf of the ESTHER-1 and ESTHER-2 trial
group. 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). Poster presented at 32nd Annual Meeting
of the European Society of Human Reproduction and Embryology (ESHRE) in
Helsinki, 3–6 July 2016. Hum Reprod. 2016;31(Supp 1):i376.

12. 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.

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

14. 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.

15. 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.

16. 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