New Evidence Shows incidence of Colo-rectal Cancer may be Reduced in Patients with Ulcerative Colitis

Munich, Germany – 28 November, 2003 –

Healthcare providers have key role to ensure patients realise benefits of mesalazine acid treatment

Over one million Europeans suffer from IBD, or inflammatory bowel disease of the colon and rectum. Patients who don’t take their medication, thereby receiving ‘no therapy’ are at higher risk of developing cancer of the large colon and rectum (colo-rectal cancer) and by simply ensuring that they take their prescribed medication as recommended by their doctors this risk may be reduced.¹

The link between developing colo-rectal cancer in patients with IBD, such as ulcerative colitis and Crohn’s disease has long been recognised, with estimates putting the risk as six to ten times greater than that of the general population.²

According to the world’s leading gastroenterologists, presenting at the Ferring sponsored “6th IBD and Salicylates” meeting in Munich, Germany (28/29th November 2003), colo-rectal cancer is the most common form of cancer that develops in this group of patients. As many as 30 percent of IBD patients with inflammation affecting the whole of the colon (pancolitis) go on to develop colorectal cancer after an average of 35 years, and at a much earlier age than seen in the general population.³ Yet so far, monitoring strategies aimed to reduce this risk have proved unsatisfactory.

But, all this could be set to change. Recent research presented at the meeting indicated that the increased risk of colo-rectal cancer seen in patients with IBD can be reduced to that of the general population (around three percent) by improving patient medication-taking (compliance) and treating them with a medication called 5-aminosalicylate (5-ASA) also known as mesalazine.*⁴

“This latest evidence reinforces earlier observations”, explained Dr Stephen Hanauer, director of the Gastroenterology and Nutrition section of the University of Chicago’s Pritzker School of Medicine. “It looks like treatments containing mesalazine could become the most cost-effective and successful way of preventing the development of, and deaths from, colo-rectal cancer in this group of patients”.

“However, our research also shows that it is essential for patients to be fully educated about the importance of fully complying with their maintenance treatment if they are to receive the full range of long-term benefits from 5-ASA-based therapies. To be most effective, the patient needs to be told that they must take their medication regularly and as prescribed, even when they are feeling well and their IBD is in remission.”

Inflammatory disease of the colon and rectum characterised by diarrhoea, pain and loss of weight is often difficult to diagnose in its early stages. It cycles through periods of activity (ranging from mild to severe), when the inflammation flares up, and remission, tempting patients to stop taking their medication during the periods when they feel better.

“Non-compliance with prescribed medication is high amongst these patients”, said Dr Jayne Eaden, consultant gastroenterologist at the Walsgrave Hospital in Coventry, England. “As many as six out of ten patients discontinue treatment, despite the fact that the 5-ASA class of medication is very well-tolerated and has low levels of side-effects.”

The risk of a patient with IBD developing colo-rectal cancer is dependent upon a number of factors. These include the age of the patient when the disease first started, how long they have had the disease, how much of the intestine is affected by the disease and whether they have a family history of colo-rectal cancer.

Dr Eaden added, “Although such patients already undergo regular screening and biopsies, such procedures are not 100 percent reliable and it is felt that the use of mesalazine would be a better way to prevent the development of colo-rectal cancer”.

“The greatest degree of protection comes to patients who take their medication properly in addition to seeing their doctors regularly for check-ups and reviews. All steps under direct control of the patient.”

There is a range of evidence to suggest that the changes linked to colo-rectal cancer occur slowly over a long time period according to Professor Christophe Gasche associate professor of medicine at the University of Vienna, in Austria. “This time window allows physicians to counteract cancer development by chemo-prevention.”

“Mesalazine helps control IBD by dampening down the inflammation that occurs in the intestines. It is not clear why it should reduce the risk of colo-rectal cancer, but it is thought that it may prevent tumours developing by inhibiting the growth of cancerous cells and encouraging their death. It may also stabilise the cell’s DNA template reducing the chance of mutations.” he added.

In addition, the outstanding research work of two European doctors was also acknowledged at the meeting. Dr Fellermann from Germany and Dr Esteve of Spain, shared the “Ferring Fellowship” for their scientific contribution to the field of IBD. The Fellowship which they are to share took the form of a € 15,000 financial award to be used for further scientific activities.

Notes for editors

*The anti-cancer benefits of mesalazine were first proposed in the mid 1990s, when it was seen that the numbers of cases of colo-rectal cancer in Danish ulcerative colitis patients, where mesalazine had been the mainstay of treatment for many years, was considerably lower than the numbers in other parts of Europe.⁵

The 6th IBD and Salicylate Symposium, attended by over 700 of the world’s leading scientists and doctors in the field of gastroenterology, is part of Ferring’s commitment to create world-wide research alliances and encourage the dissemination of ground-breaking work in the field of inflammatory colo-rectal disease.

Ferring Pharmaceuticals markets PENTASA, a prolonged release 5-ASA in more than 50 markets world-wide.

About Ferring Pharmaceuticals

Ferring is a research driven, speciality biopharmaceutical group active in global markets.  The company identifies, develops and markets innovative products in the areas of endocrinology, gastroenterology, gynecology, infertility and urology.

In recent years Ferring has expanded beyond its traditional European base and now has operating subsidiaries in over 40 countries.

To learn more about Ferring or our products please visit us at
www.Ferring.com.

For more information, please contact

Sharmi Albrechtsen
Ferring International Center
+45 28 78 72 09
sharmi.albrechtsen@ferring.com

References

1. 1. Kane S, Huo D, Aikens J, Hanauer S. Medication non adherence and the outcomes of patients with quiescent ulcerative colitis. Am J Med. 2003 Jan;114(1):39-43.
   2. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001 Apr;48(4):526-35.
   3. Ekbom A et al. The New England Journal of Medicine 1990, Nov 1,323 (18), 1228-33.
   4. Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J. Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment Pharmacol Ther. 2000 Feb;14(2):145-53.
   5. Munkholm P et al. Aliment Pharmacol Ther 2003; 18 (Suppl. 2): 1-5.

New infertility study – Significant difference between treatments

San Antonio, USA – October 15th, 2003 –

New results from a large multicenter study indicate that women undergoing IVF¹ treatment with MENOPUR² have a remarkable improved chance of becoming pregnant vs. women treated with recombinant FSH.³ MENOPUR contains a combination of hormones similar to those present in the natural reproductive cycle. MENOPUR is approved in 26 countries around the world and is currently under investigation in the United States.

Data from an international study involving 727 patients in ART⁴, show a significantly increased number of pregnancies following treatment with MENOPUR compared to recombinant FSH therapy in a group of women undergoing IVF. The data show that 31% of women in the MENOPUR group became pregnant vs. only 20% of patients in the recombinant FSH. The results were unveiled today at the American Society for Reproductive Medicine Annual Congress, ASRM, in San Antonio, USA.

MENOPUR contains a combination of hormones with Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH⁵) activity similar to those involved in the natural reproductive cycle. According to Dr. Pascal Danglas, Executive Vice President
Clinical and Product Development, Ferring Group, the LH activity is the key difference between the two treatments. According to the most prevalent reproductive theories both FSH and LH activity are necessary for successful egg maturation and implantation. This combination is part of the explanation for the improved pregnancy rates.

“The outcome of the study is very important. Infertility treatment is an exhausting process for an infertile couple – both physically and psychologically. A 50% increase in pregnancy rate must be considered a major improvement and should be studied further”, says Dr. Pascal Danglas.

14% of couples are facing problems with infertility and the number is increasing, mainly because many women are opting to postpone motherhood. In the group of 30-35 year olds, the infertility rate increases to 25%. One third of births are by women above 30 years of age.

Today, reproductive medicine offers a variety of procedures to assist couples in achieving pregnancy, but more than half of the couples with more than two years of infertility treatment still fail to achieve pregnancy. With advances in infertility research and wider availability of newer techniques, the success rate of infertility treatment is going up but there is a continuous need for new and more effective treatments. Based on the results of this study, MENOPUR must be considered one of the most effective IVF therapies today.

Ferring manufactures a wide range of infertility products as well as medicine for delaying preterm birth. The company continues the research and development of new products within infertility and obstetrics.

“The combination of FSH and LH activity is an important contributor to egg maturation and implantation, and as such MENOPUR represents an opportunity to mimic the natural reproductive cycle. Ferring is dedicated to successful pregnancies and continues research activities into the mechanisms of infertility. In the light of the findings in this study additional prospectively-designed clinical trials to further evaluate the benefits of MENOPUR are being initiated”, says Michel Pettigrew, Chief Operating Officer of the Ferring Group.

Ferring was established in Europe but operates globally today. The company employs more than 2,200 people in 40 countries.

About Ferring Pharmaceuticals

Ferring is a research driven, speciality biopharmaceutical group active in global markets.  The company identifies, develops and markets innovative products in the areas of endocrinology, gastroenterology, gynecology, infertility and urology.

In recent years Ferring has expanded beyond its traditional European base and now has operating subsidiaries in over 40 countries.

To learn more about Ferring or our products please visit us at
www.Ferring.com.

References

1. 1. In Vitro Fertilization (IVF) — Literally means “in glass.” Fertilization takes place outside the body in a small glass dish.
   2. MENOPUR is a registered trademark of Ferring BV and/or its affiliates.
      MENOPUR — is the highly purified menotropin preparation and provides high quality and cost-effective treatment for infertile couples. MENOPUR contain equal amounts of FSH and LH activity (75 IU FSH and 75 IU LH). MENOPUR is used to treat women with anovulation, to stimulate ovarian follicular development, as well as to treat infertility in men with hypo- or normagonadotropic hypogonadism, and in combination with hCG to stimulate spermatogenesis. MENOPUR is currently under investigation in the United States.
   3. Follicle Stimulating Hormone (FSH) — A pituitary hormone that stimulates spermatogenesis and follicular development. In the man FSH stimulates the Sertoli cells in the testicles and supports sperm production. In the woman FSH stimulates the growth of the ovarian follicle. Elevated FSH levels are indicative of gonadal failure in both men and woman.
   4. Assisted Reproductive Technology (ART) — Several procedures employed to bring about conception without sexual intercourse, including IUI, IVF, GIFT and ZIFT.
   5. Luteinizing Hormone (LH) — A pituitary hormone that stimulates the gonads. In the man LH is necessary for spermatogenesis (Sertoli cell function) and for the production of testosterone (Leydig cell function). In the woman LH is necessary for the production of estrogen. When estrogen reaches a critical peak, the pituitary releases a surge of LH (the LH spike), which releases the egg from the follicle.
   6. Gonadotropins — Hormones that control reproductive function: e.g. Follicle Stimulating Hormone and Luteinizing Hormone.

Ferring grants Dr. Frederik Paulsen Memorial Award in Japan

Copenhagen, Denmark – 22 September, 2003 –

Earlier this month, Ferring Pharmaceuticals granted the Dr. Frederik Paulsen Memorial Award in Neurosciences. The award winner, Dr. Yamashita from the Tokyo Medical and Dental University, received the award for the best poster at the World Congress of Neurohypophysis Research (WCNR) in Tokyo, Japan.

Dr. Yamashita’s poster described her research in identifying several proteins in the kidney that are involved in regulation of water transport in the kidney and concentration of urine.

‘Research in this area will hopefully in the future make it possible for us to further determine ways of modulating urine production, giving us safer and more predictable medicines in voiding dysfunction as Nocturia, bedwetting and possibly also incontinence,’ said Dr. Jens Peter Nørgaard, Executive Director, Medical Sciences, Urology.

The award was launched this year in the field of Neurohypophysis Research to commend scientific endeavours of special interest to Dr. Paulsen, the founder of Ferring. Dr. Paulsen was particularly intrigued by the pituitary gland and the use of neuropeptide hormones in medicines.

“Dr. Frederik Paulsen was a pioneer in this area. He welcomed the freedom to explore new avenues of research especially with regards to peptides,” said Dr. Nørgaard.

Many of Ferring’s products today are related to neurohypophysis work including vasopressin, oxytocin, growth hormone, ACTH, FSH and GNRH. “Ferring has been involved with multidisciplinary research since 1952 and has contributed to defining the impact that urinary production has for social continence”, said Dr. Nørgaard.

The WCNH aims to promote and advance the fields neurohypophysial hormones and related active substances in the brain, kidney and reproductive organs and to enhance the ties among scientists in the world.

About Ferring Pharmaceuticals

Ferring is a research driven, speciality biopharmaceutical group active in global markets.  The company identifies, develops and markets innovative products in the areas of urology, obstetrics and infertility, gastroenterology and endocrinology.  In recent years Ferring has expanded beyond its traditional European base and now has operating subsidiaries in over 40 countries.

To learn more about Ferring or our products, please visit us at www.Ferring.com.

For more information, please contact

Sharmi Albrechtsen
Ferring International Center
+45 28 78 72 09
sharmi.albrechtsen@ferring.com

Ferring Pharmaceuticals to build state of the art production site in Saint-Prex

Lausanne, Switzerland – September 12, 2003 –

Ferring Pharmaceuticals, world pioneer and leader in industrial synthetic peptides, breaks ground for a new manufacturing site in Saint-Prex, canton of Vaud. The company will invest nearly EUR 90 million in the site construction and expects to employ approximately 250 people at the site by 2008.

The future for Ferring’s new site begins today, when more than one hundred guests are scheduled to discover more about Ferring during a virtual tour at the 104,500 m2 site and attend the ground-breaking ceremony conducted by the Mayor of Saint-Prex, Günter Dauner and Ferring’s Executive Chairman, Mr. Frederik Paulsen.

Ferring established its headquarters in Lausanne in 2000. The building of new production facilities in Switzerland continues Ferring’s commitment to the region.

“I am very excited about this project. The new production site will allow us to meet a growing demand for our current products and secure the future supply of innovative new medicines that we have in development for our patients around the world”, says Mr. Frederik Paulsen, son of Ferring’s late founder Dr. Frederik Paulsen. He adds: ‘We have been delighted with the warm reception we have received in Vaud and are grateful for the whole-hearted support we have from the community and the local government”.

The building work starts this autumn, with expected completion by spring 2005 and commercial production planned for 2007. The completed building will cover 23,000 m2, including production, packaging and administration.

The design of the new building is the work of the Dolci Architecte / Tekne Management consortium in Yverdon-les-Bains and Lausanne. The 15m high building will make extensive use of natural daylight, both in the administration and production areas, through its use of glass walls as well as windows on the interior corridors.

“We chose Switzerland primarily due to the high concentration of quality personnel as well as its central location in Europe with easy access to transportation… but the natural beauty of Saint-Prex was definitely a contributing factor”, says Michel L. Pettigrew, Chief Operating Officer and adds: “Over the past years Ferring has shown a strong sales development. The new production site in Saint-Prex will make it possible for us to continue in this direction”.

Michel L. Pettigrew represents Ferring at today’s press conference at the Centre du Vieux-Moulin, Commune de Saint-Prex.

About Ferring Pharmaceuticals

Ferring is a research driven, specialty biopharmaceutical group active in global markets. The company identifies, develops and markets innovative products in the areas of endocrinology, gastroenterology, gynaecology, infertility and urology.

In recent years Ferring has expanded beyond its traditional European base and now has operating subsidiaries in over 40 countries.

To learn more about Ferring, please visit us at https://www.ferring.com.pl.

For more information, please contact

In Switzerland
Evelyne Erb
Ferring SA – Lausanne
+41 (0) 79 290 44 06
evelyne.erb@ferring.com

International
Mette Nikolajsen, Communication Officer
Ferring International Center – Copenhagen
+ 45 28 78 71 98
mette.nikolajsen@ferring.com