FDA approves Ferring’s CLENPIQ™ (sodium picosulfate, magnesium oxide, and anhydrous citric acid) oral solution for colonoscopy prep

New Ready-to-Drink Low-Volume Colonoscopy Prep in a Premixed Liquid Solution

Parsippany, NJ – November 29, 2017 –

The U.S. Food and Drug Administration (FDA) has granted Ferring Pharmaceuticals Inc. approval to market CLENPIQ™ (sodium picosulfate, magnesium oxide, and anhydrous citric acid) oral solution for cleansing of the colon in adults undergoing a colonoscopy. With availability planned in Q1 2018, CLENPIQ will be the only FDA-approved prescription colonoscopy prep that comes “ready-to-drink”.

Colorectal cancer is the third most common cancer and second leading cause of cancer death in the United States.¹ Colonoscopies can help reduce the incidence of colorectal cancer and deaths associated with this disease.^2,3,4

“Successful bowel prep is critical for gastroenterologists to clearly see the inside of the colon during a colonoscopy. The sheer volume of a prescribed bowel prep solution can be a barrier for some patients to adequately complete their prep regimen, leading to suboptimal visualization of the colon,” said Dr. Edward Brettholz, Clinical Assistant Professor of Medicine, NYU School of Medicine. “Having a ready-to-drink, low volume colonoscopy prep in a pre-mixed oral solution is an excellent start to prepare patients for this important procedure to help detect and prevent colorectal cancer.”

“We are delighted to add CLENPIQ to our gastroenterology portfolio,” said Paul Navarre, CEO, Ferring Holding Inc. “We expect that a ready-to-drink bowel preparation will aid physicians in their efforts to encourage colonoscopies among a patient population for whom various public health initiatives have called for increased screening.”

About CLENPIQ

CLENPIQ is a ready-to-drink cranberry-flavored, dual-acting, combination of sodium picosulfate, a stimulant laxative, and magnesium oxide and anhydrous citric acid, which forms magnesium citrate, an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults.⁵

Important Safety Information

• CLENPIQ is contraindicated in the following conditions: patients with severe renal impairment (creatnine clearance less than 30mL/minute), gastrointestinal obstruction or ileus, bowel perforation, toxic colitis or toxic megacolon, gastric retention, or in patients with a known hypersensitivity to any of the ingredients in CLENPIQ.
• Patients should be advised to hydrate adequately (before, during and after use of CLENPIQ), and post-colonoscopy lab tests should be considered if a patient develops significant vomiting or signs of dehydration, including orthostatic hypotension, after taking CLENPIQ. Patients with electrolyte abnormalities should have them corrected before treatment. Use caution when prescribing CLENPIQ for patients that have conditions or are using medications that may increase the risk for fluid and electrolyte abnormalities.
• Use caution in patients who have conditions, or are taking concomitant medications that increase the risk for seizures, such as those taking medications that lower the seizure threshold, patients withdrawing from alcohol or benzodiazepines or patients with known or suspected hyponatremia.
• Use caution in patients with impaired renal function or taking medications that may affect renal function, as well as patients at increased risk of arrhythmias, including those patients with a history of prolonged QT, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy.
• Osmotic laxatives may produce colonic mucosal aphthous ulcerations and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Concurrent use of additional stimulant laxatives with CLENPIQ may increase this risk.
• Use with caution in patients with severe active ulcerative colitis.
• Use with caution in patients with impaired gag reflex as they may be at risk for regurgitation or aspiration during administration of CLENPIQ.
• The safety of CLENPIQ has been established from adequate well controlled trials of another formulation of sodium picosulfate, magnesium oxide and anhydrous citric acid. The most common adverse reactions in those trials were nausea, headache, and vomiting.
• CLENPIQ can reduce the absorption of co-administered drugs. Do not take oral medications within one hour of starting CLENPIQ. Administer tetracycline and fluoroquinolone antibiotics, iron, digoxin, chlorpromazine and penicillamine, at least 2 hours before and not less than 6 hours after administration of CLENPIQ to avoid chelation with magnesium.

You are encouraged to report negative side effects of prescription drugs to FDA.

Visit www.FDA.gov/medwatch, or call 800.FDA.1088.

For full prescribing information, please visit: www.CLENPIQ.com

About Ferring Pharmaceuticals Inc. Ferring Pharmaceuticals is a research-driven biopharmaceutical company devoted to identifying, developing and marketing innovative products in the fields of reproductive health, urology, gastroenterology, endocrinology and orthopaedics. For more information, call 1-888-FERRING (1- 888-337-7464); visit www.FerringUSA.com or www.CLENPIQ.com

Ferring acquired global rights (excluding Korea) to the stable liquid formulation used in CLENPIQ from Pharmbio Korea co., Ltd.

FERRING, the FERRING PHARMACEUTICALS logo, and CLENPIQ are trademarks of Ferring B.V.

For more information, please contact

Ana Fullmer
ana.fullmer@bm.com
202-530-4662

References

1. U.S. Center for Disease Control and Prevention. Colorectal Cancer Statistics. https://www.cdc.gov/cancer/colorectal/statistics/index.htm. Last updated: March 23, 2017.
2. American Cancer Society. Colorectal Cancer Facts & Figures 2017-2019. Atlanta: American Cancer Society; 2017.
3. Brenner, et al. Potential for Colorectal Cancer Prevention of Sigmoidoscopy Versus Colonoscopy: Population- Based Case Control Study. Cancer Epidemiol Biomarkers Prev. 2007; 16:494-499.
4. Khai, et al. Effect of Screening Colonoscopy on Colorectal Cancer Incidence and Mortality. Clinical Gastroenterology and Hepatology. 2009; 7:770–775.
5. CLENPIQ™ [Prescribing Information]. Parsippany, NJ: Ferring Pharmaceuticals Inc.

New Ferring and Aché Laboratórios Farmacêuticos facility opens to optimise drug delivery using nanotechnology

• Research begins in São Paulo to explore the role of nanotechnology as a delivery system for future medicines
• Anticipated that nanotechnology will improve the bioavailability, efficacy and safety of oral medicines
• Initial research areas to cover reproductive medicine and women’s health, gastroenterology and urology

Saint-Prex, Switzerland – 29 November 2017 –

Ferring Pharmaceuticals and Aché Laboratórios Farmacêuticos today announced the inauguration of their joint nanotechnology centre in São Paulo, Brazil. Focused exclusively on nanotechnology research and development, the centre forms the first phase in a long term collaboration to optimise patient care through enhanced drug delivery systems and product solutions.

The Nanotechnology Innovation Laboratory Enterprise (NILE) centre and associated research programme will explore nanotechnology to advance the delivery characteristics of existing medicines, create novel devices and find new formulations for poorly soluble drugs. For example, for patients who currently receive treatment by injection, this new technology has the potential to transform their ongoing care with new oral options. Researchers will investigate how nanotechnology might improve the bioavailability, efficacy and safety profile of oral medicines, and alleviate any unwanted toxicity resulting from non-specific distribution.

Initial research projects will utilise each company’s therapeutic strengths. Ferring will provide expertise on peptides and proteins in reproductive medicine and women’s health, gastroenterology and urology, and Aché will provide knowledge on how to expedite the development of new therapeutic entities with different technical properties.

“Using nanotechnology to administer peptide and protein-based medicines orally could be a significant step forward for the ease of delivery for this important class of drugs,” said Alan Harris, Senior Vice President, R&D, Ferring Pharmaceuticals. “Ferring’s pioneering work in reproductive medicine and women’s health is devoted to providing next generation solutions that improve outcomes and better serve the needs of our patients. If we can provide patients with more convenient dosing, we will help to improve adherence and ensure that patients receive the greatest benefit from treatment.”

“In recent years, considerable investment has been made in Brazil to harness the potential of nanotechnology. Our established strength in using radical innovation to create new assets, whether synthetic, herbal, biologicals or nutraceuticals, combined with the rich source of natural compounds existing within Brazilian biodiversity, places us in a unique position to lead future cutting-edge science,” said Stephani Saverio, head of Innovation of Aché. “Nanotechnology has huge potential to address the challenges associated with today’s drug delivery systems and to optimise future care.”

The NILE centre is anticipated to be a global hub for future drug discovery and development. The inauguration ceremony brought together leading experts from the field of nanotechnology as well as dignitaries from the Ministry of Health of Brazil and government officials.

– ENDS –

About Nanotechnology

Nanotechnology is a branch of technology focused on understanding and controlling matter at the very smallest scales. At nanoscale, properties can be very different when compared to those with which we are familiar. Such properties mean that nanotechnology has the potential to optimise current drug delivery technologies, and offers many opportunities to create new drug delivery systems, formulations for poorly soluble drugs and novel devices. In addition to the potential advantages of enhancing systemic administration, nanoparticulate drug delivery systems can also be used for site-specific delivery, thus alleviating unwanted toxicity due to nonspecific distribution, helping to improve patient compliance and provide favourable clinical outcomes. Nanotechnology platforms will help in the development of advanced drug-delivery systems to decrease the failure rate of new active pharmaceutical ingredients (APIs), bio-therapeutic agents and vaccines caused by poor absorption, or distribution, significant drug toxicity, and rapid metabolism or excretion.

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.

Ferring is on Twitter. Follow us @FerringNews at http://twitter.com/FerringNews

About Aché Laboratórios Farmacêuticos

Aché is a 100% Brazilian company with more than 50 years of operation in the pharmaceutical market with the objective of bringing more life to the persons, wherever they are. It has three industrial sites: Guarulhos (SP), São Paulo (SP), and Londrina (PR), and participation in Melcon do Brasil, and Bionovis, a Brazilian joint venture dedicated to research and development of biotechnology medicines. It employs 4,600 people and has one of the largest demand and sales generation forces in the pharmaceutical sector in Brazil. In order to meet the needs of healthcare professionals and consumers, Aché offers a portfolio of 326 brands in 804 submissions for prescription, generic and OTC (non-prescription) drugs, and it also acts in the segments of skin cosmetics, nutraceuticals, probiotic and biological segments. Ache´s focus on innovation has been developing attractive products currently present in 20 countries of the Americas, Africa, and Asia. Ache´s innovative products are being developed for registration in the world´s most regulated markets.

To know more about Aché, please visit www.ache.com.br.

For more information, please contact

Lindsey Rodger
Senior Manager, Corporate Communications
+41 58 451 4023 (direct)
+41 79 191 0486 (mobile)
lindsey.rodger@ferring.com

Bhavin Vaid
Head of Corporate Communications
+41 58 301 0952 (direct)
+41 79 191 0632 (mobile)
bhavin.vaid@ferring.com

Aché Laboratórios Farmacêuticos

Press Information:

CDI Corporative Communication

Renata Lopes +55 (11) 3817-7994 – renata.lopes@cdicom.com.br

Flavia Tavares +55 (11) 3817-7914 – flavia@cdicom.com.br

Cláudia Santos +55 (11) 3817-7925 – claudia@cdicom.com.br

Ferring receives Swiss approval for Rekovelle®, the first personalised fertility treatment using an approved dosing algorithm

• Rekovelle^® provides doctors with an approved, evidence-based, individualised dosing regimen to personalise fertility treatment

• Approval expands options for fertility patients in Switzerland, providing a new and tailored approach to help doctors achieve target ovarian response

• Approval is based on a comprehensive clinical development programme (ESTHER), involving patients in 11 countries and over 2,000 treatment cycles

Saint-Prex, Switzerland – 27 November, 2017 –

Ferring Pharmaceuticals announced today that Swissmedic has approved Rekovelle^® (follitropin delta) for use in controlled stimulation for induction of the development of multiple follicles in women undergoing assisted reproductive technologies (ART), such as an in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).¹ Rekovelle is a new human recombinant follicle stimulating hormone (human rFSH) and the first to use an approved individualised dosing regimen, based on a woman’s anti-Müllerian hormone (AMH) level and body weight.^1,2

“With Ferring’s headquarters in Switzerland, we are particularly proud to announce the Swissmedic approval of Rekovelle, the first fertility medication to offer women a personalised approach, right from the start of treatment,” said Michel Pettigrew, President of the Executive Board and Chief Operating Officer, Ferring Pharmaceuticals. “The addition of Rekovelle to Ferring’s reproductive health portfolio reflects our ongoing commitment to addressing unmet patient needs at each stage of the fertility journey, from conception to birth.”

The Swissmedic approval was based on data from 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 patients in 11 countries and over 2,000 cycles of controlled stimulation, also known as controlled ovarian stimulation (COS).^2,3 The data showed that women receiving individualised treatment with Rekovelle, compared to conventional dosing with follitropin alfa*, had similar ongoing pregnancy and embryo implantation rates. Secondary endpoints^✝ showed that 43% of women treated with Rekovelle achieved the target ovarian response of 8–14 oocytes (eggs), compared to 38% of women treated with follitropin alfa. Rekovelle’s individualised dosing regimen aims to obtain an ovarian response associated with a favourable safety/efficacy profile, i.e. aims to achieve an adequate number of eggs and reduce interventions to prevent ovarian hyperstimulation syndrome (OHSS). This dosing regimen is specific to Rekovelle and cannot be applied to other fertility treatments.

– ENDS –

* GONAL-f®, registered trademark of Merck KGaA, Darmstadt, Germany

✝ESTHER-1 was neither designed nor powered to assess results based on secondary endpoints. Predefined secondary endpoints are used as a measurement to yield supportive evidence to evaluate additional effects relevant to informing the Rekovelle individualised dosing regimen. No confirmatory conclusions can be derived.

About Rekovelle (follitropin delta)

Rekovelle is the first recombinant follicle stimulating hormone (rFSH) derived from a human cell line (PER.C6^® cell line). Rekovelle is structurally and biochemically distinct from other existing rFSH treatments.^1,4 The individualised dosing of Rekovelle is determined using an approved algorithm, based on a woman’s anti-Müllerian hormone (AMH) level and body weight.^1,2,5 AMH will be measured by a companion diagnostic, the Elecsys^® AMH Plus immunoassay from F. Hoffmann-La Roche Ltd (Roche).^6,7

Rekovelle is currently approved in 34 countries and is available in 11 countries worldwide.

About controlled ovarian stimulation

Controlled stimulation, or controlled ovarian stimulation (COS), is the process by which a pharmacological treatment is used to induce the development of multiple ovarian follicles to obtain multiple eggs at follicular aspiration (egg retrieval from the ovaries). COS is required prior to assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).⁸

About anti-Müllerian hormone (AMH) and ovarian hyperstimulation syndrome (OHSS)

AMH is a biomarker used to assess ovarian reserve and can help predict ovarian response.⁹ Women with high AMH levels are at an increased risk of developing OHSS, a potential complication of IVF treatment.^10,11 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.¹⁰

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.¹² A recent report suggested that OHSS is an underreported side effect of COS and the real world incidence may be higher.¹³ In addition to the impact on patients, the treatment of OHSS is associated with significant costs to the healthcare system.¹⁴ In the UK for example, the cost of treating moderate and severe cases of OHSS is estimated to be over £7 million (over 9 million CHF) every year.^14,15

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.^2,3

ESTHER-1 was a trial of 1,326 patients in 11 countries undergoing their first ART cycle. Patients were randomised 1:1 to receive treatment with individualised Rekovelle, a fixed daily dose based on serum 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.² Results of the ESTHER-1 trial were published in the February 2017 issue of Fertility & Sterility.²

ESTHER-2 evaluated the immunogenicity of Rekovelle in a subset of ESTHER-1 patients undergoing repeated cycles of COS for ART. Data demonstrated no increased immunogenicity risk with Rekovelle after exposure in repeated cycles.³

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, including Ferring AG based in Baar, Switzerland which was founded in 1984. Ferring AG is responsible for the distribution and marketing of Ferring products in Switzerland and Liechtenstein. 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.^{6,7,16,17,18,19} 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 Ferring follitropin delta in combination with body weight in COS for the development of multiple follicles in women undergoing an assisted reproductive technology programme.^{1,6,7,16,17,18,19}

For more information, please contact

Lindsey Rodger
Senior Manager, Corporate Communications
+41 58 451 40 23 (direct)
+41 79 191 0486 (mobile)
lindsey.rodger@ferring.com

Bhavin Vaid
Head of Corporate Communications
+41 58 301 09 52 (direct)
+41 79 191 06 32 (mobile)
bhavin.vaid@ferring.com

References

1. Rekovelle® Product Information, Switzerland.
2. 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.
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. 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.
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;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. http://www.cobas.com/content/dam/cobas_com/pdf/product/Elecsys%20AMH/Elecsys%20AMH%20FactSheet.pdf.  [Last accessed October 2017].
8. Zegers-Hochschild  F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, Sullivan E, Van der Poel S. The international committee for monitoring assisted reproductive technology (ICMART) and the world health organization (WHO) revised glossary on ART terminology, 2009. Human reproduction. 2009;24(11): 2683-7.
9. 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.
10. Mayo Clinic. OHSS Symptoms and Causes. Patient Care and Health Information. Available at: http://www.mayoclinic.org/diseases-conditions/ovarian-hyperstimulation-syndrome-ohss/symptoms-causes/dxc-20263586. [Last accessed: October 2017].
11. 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.
12. Delvigne A, Rozenberg S, et al. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002;8(6): 559-577.
13. Thomsen L, Humaidan P, et al. Ovarian hyperstimulation syndrome in the 21st century: the role of gonadotropin-releasing hormone agonist trigger and kisspeptin. Curr Opin Obstet Gynecol. 2015;27(3): 210-214.
14. Thomsen L, Humaidan P, et al. Ovarian hyperstimulation syndrome in the 21st century: the role of gonadotropin-releasing hormone agonist trigger and kisspeptin. Curr Opin Obstet Gynecol. 2015;27(3): 210-214.
15. Human Fertilisation and Embryology Authority. Fertility Treatment in 2014 Trends and Figures Report. Available at: http://ifqtesting.blob.core.windows.net/umbraco-website/1111/hfea-fertility-treatment-trends-and-figures-2014.pdf [Last accessed: October 2017]
16. Gassner D, Jung R. First fully automated immunoassay for anti-Müllerian hormone. Clin Chem Lab Med. 2014;52(8): 1143-52.
17. 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.
18. 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.
19. 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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Fertility Infographic