Ferring announces European approval of new room temperature stable formulation of PABAL® (carbetocin)

Ferring announced today that its new room-temperature-stable* formulation of PABAL^® (carbetocin) for intravenous (IV) administration has been approved through the EU Mutual Recognition Procedure. PABAL is a long-acting synthetic analogue of human oxytocin with a half-life of approximately 40 minutes¹ and is indicated for the prevention of uterine atony following delivery of the infant by caesarean section under epidural or spinal anaesthesia.² The new formulation of PABAL is the first long-acting, room-temperature-stable oxytocic agent to be approved for this condition. Room-temperature-stable PABAL is expected to become available in Europe during the second quarter of 2015.

Uterine atony, or lack of muscle tone in the uterus, is responsible for approximately 80% of postpartum haemorrhage (PPH) cases.^3,4 PPH is defined as a bleed of 500 mL or more in vaginal deliveries and in excess of 1000 mL in abdominal deliveries.⁵ International and national guidelines agree that active management of the third stage of labour is a key factor in preventing PPH.^5-10 This is often achieved with uterotonic agents like oxytocin, ergometrine, syntometrine and the other formulations of carbetocin,^2,11-13 all of which require refrigeration from manufacture, through distribution, storage and eventual use.^10,14,15

“Preventing uterine atony saves lives,” said Pascal Danglas, MD, Executive Vice President and Chief Medical Officer at Ferring Pharmaceuticals. “By removing the necessity of refrigeration, Ferring aims to make PABAL more easily accessible. Expanding access to such medications is central to our commitment to women’s health globally.”

Based on the results obtained in stability studies, the new formulation has a recommended storage and shelf-life of 24 months at 30ºC and 75% humidity,¹⁶ which may be helpful in low-income countries where cold-chain storage and transport may not be available.¹⁷

Ferring, MSD (known as Merck in the United States and Canada) and the World Health Organization (WHO) are working together with the aim of making the room-temperature-stable formulation of carbetocin for intramuscular administration available in the public sector of developing countries that have a high burden of maternal morbidity and mortality, at an affordable and sustainable price. As part of this collaboration, WHO will conduct a multi-country clinical trial to evaluate the effectiveness of this formulation (as compared to oxytocin) in preventing uterine atony in the third stage of labour in women who have delivered vaginally. The study will take place in 11 countries around the world and enrol approximately 30,000 women.

*Keep vials in the outer carton, in order to protect from light. Store below 30°C. Do not freeze. ²

-Ends-

Notes to the editor

Carbetocin 100 micrograms/mL solution for injection is marketed by Ferring B.V. and/or one of its affiliates, dependent on country, with one of the following registered trademarks: PABAL^®, DURATOCIN^®, LONACTENE^®, LONACTENE^® RT and DURATOBAL^®.

About PABAL ^®

Since its introduction in 1999, PABAL has been approved for the prevention of uterine atony in over 70 countries. With a single 100mcg IV dose, it stimulates uterine contractility within two minutes, and sustains rhythmic contractions for one hour.¹⁸ It raises uterine tone and provides protection against uterine atony for up to 48 hours, thus reducing the risk of blood loss.¹⁹ In women undergoing caesarean section, PABAL significantly reduces the need for additional uterotonics and additional uterine massage compared with oxytocin.²⁰ Carbetocin may also be associated with lower levels of perceived post-operative pain following caesarean delivery than oxytocin.²¹ Room temperature stable PABAL is available in vials containing 1ml and can be stored at up to 30^oC.²

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.

Pregnancy and childbirth pose significant health risks even in the developed world and more so in the developing world. This is reflected by global initiatives to significantly improve maternal and neonatal health by 2015 via the Millennium Development Goals.²² It has been estimated that 40% of women experience pregnancy-related health problems during or after pregnancy and childbirth, with 15% suffering serious or long-term complications.²³ The management of such risks necessitates continued research and development in obstetrics. Ferring is dedicated to improving obstetric therapies, from the management of preterm labour and induction of labour to prevention of PPH, to reduce undesirable maternal and neonatal risks during pregnancy.

All trademarks mentioned above are property of Ferring B.V.

Ferring International Center S.A., Chemin de la Vergognausaz 50, 1162 Saint-Prex, Switzerland

Tel: +41 58 301 00 00, Fax: +41 58 301 00 10, www.ferring.com

PL/426/2015/CH3

References

1. Sweeney G, Holbrook AM, Levine M, et al. Pharmacokinetics of carbetocin, a long acting oxytocin analogue, in nonpregnant women. Curr Ther Res 1990;47:528–540.

2. PABAL Summary of Product Characteristcs (SmPC): Available at: https://www.medicines.org.uk/emc/medicine/17274 (Last accessed February 2015)

3. Callaghan WM, Kuklina EV, Berg CJ. Trends in postpartum hemorrhage: United States,1994–2006. Am J Obstet Gynecol 2010;202:353 e351–356.

4. Mehrabadi A, Liu S, Bartholomew S, et al. Temporal trends in postpartum hemorrhage and severe postpartum hemorrhage in Canada from 2003 to 2010. J Obstet Gynaecol Can 2014;36:21–33.)

5. World Health Organization. WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage 2012. Available at http://apps.who.int/iris/bitstream/10665/75411/1/9789241548502_eng.pdf (Last accessed February 2015).

6. Lalonde A; International Federation of Gynecology Obstetrics. Prevention and treatment of postpartum hemorrhage in low-resource settings. Int J Gynaecol Obstet 2012;117:108–118.

7. Leduc D, Balleman C, Biringer A, et al. Society of Obstetricians and Gynaecologists of Canada. Active management of the third stage of labour: prevention and treatment of postpartum hemorrhage. Int J Gynaecol Obstet 2010;108:258–267

8. ACOG Committee on Practice Bulletins – Obstetrics. ACOG Practice Bulletin No. 76. Postpartum haemorrhage. Obstet Gynecol 2006; 108: 1039-1047

9. Royal College of Obstetricians and Gynaecologists. RCOG Green-top Guieline No. 52: Prevention and Management of Postpartum Haemorrhage 2009. Available at: http://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg52/ (Last accessed February 2015)

10. Queensland Maternity and Neonatal Clinical Guidelines Program. Maternity and Neonatal Clinical Guideline: Primary postpartum haemorrhage 2012. Available at: http://www.health.qld.gov.au/qcg/documents/g_pph.pdf. (Last accessed February 2015).

11. Mayne Pharmaceuticals. Oxytocin Summary of Product Characteristics (SPC) 2010. Available at: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con079194.pdf (Last Accessed March 2015).

12. Hameln Pharmaceuticals LTD. Ergometrine Injection BP 0.05% w/v 2015. Available at: https://www.medicines.org.uk/emc/medicine/20884 (Last Accessed March 2015).

13. Alliance Pharmaceuticals. Syntometrine Ampoules Summary of Product Characteristics (SPC) (eMC) 2014. Available at: https://www.medicines.org.uk/emc/medicine/135 (Last Accessed March 2015).

14. Centro Nacional de Excelencia Tecnológia en Salud: CENETEC. Prevención y manejo de la hemorragia postparto en el primero y segundo nivel de atención. 2008. Available at: http://www.isssteags.gob.mx/guias_praticas_medicas/gpc/docs/SSA-103-08-ER.pdf. (Last accessed February 2015).

15. Poręba R, Oszukowski P, Oleszczuk J, et al. Extended position statement by the Expert Group of the Polish Gynaecological Society on the use of carbetocin in the prevention of postpartum haemorrhage. GinPolMedProject 2013;1:41–57.

16. Ferring Pharmaceuticals. Data on file. eCTD document Q-3.2.P.8.1 Stability Summary and Conclusion-9203 section 3.2.P.8.1.2. 2014.

17. World Health Organization. Priority Medicines for Europe and the World Update Report. 2013. Available at: http://www.who.int/medicines/areas/priority_medicines/Ch6_0Intro.pdf (Last accessed February 2015).

18. Hunter DJ, et al. Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus. Clin Pharmacol Ther 1992;52:60–7.

19. Dansereau J, et al. Double blind comparison of carbetocin versus oxytocin in prevention of uterin atony after caesarean section. Am I Obstet Gynecol 1999; 180:670-6

20. Su LL, Chong YS, Samuel M. Carbetocin for preventing postpartum haemorrhage. Cochrane Database Syst Rev 2012; 4:CD005457

21. De Bonis M, Torricelli M, Leoni L, et al. Carbetocin versus oxytocin after caesarean section: similar efficacy but reduced pain perception in women with high risk of postpartum haemorrhage. J Matern Fetal Neonatal Med 2012;25:732–735.

22. United Nations. Goal 5: Improve Maternal Health Fact Sheet. 2010. Available at: http://www.un.org/millenniumgoals/pdf/MDG_FS_5_EN_new.pdf (Last accessed February 2015).

23. United Nations. Press release: UN Agencies Issue Joint Statement for Reducing Maternal Mortality. 1999. Available at: http://www.unicef.org/newsline/mmstat.htm. (Last accessed February 2015).

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Contact information

MSLGROUP London
Sarah Herbert
sarah.herbert@mslgroup.com
Tel: +44 (0) 20 3219 8708
or
Ferring Pharmaceuticals
Patrick Gorman
patrick.gorman@ferring.com
Tel: +41 (0) 58 301 00 53