Toremifene citrate 80 mg meets primary and key secondary endpoints in phase III clinical trial

...in advanced prostate cancer patients on androgen deprivation therapy Ipsen intends to submit toremifene citrate 80 mg in Europe before year-end 2008

Paris (France), 25 February 2008 — Ipsen (Euronext: IPN) announced today that GTx Inc. (NASDAQ: GTXI), from which it licensed the European rights for Acapodene^® (toremifene citrate 80 mg) in September 2006, presented the results of the first phase III study evaluating the efficacy and safety of toremifene citrate 80mg daily, on multiple side effects of androgen deprivation therapy (ADT) in advanced prostate cancer patients. On the basis of these positive results, Ipsen intends to file toremifene citrate 80 mg for this indication in the European Union before year-end 2008. Androgen deprivation therapy using either luteinizing hormone releasing hormone or surgical castration is the most common treatment for advanced prostate cancer and have clearly demonstrated their efficacy. However, their impact on testosterone and oestrogen levels could result in a decrease of bone mineral density (BMD) potentially leading to osteoporotic fractures, and other adverse effects such as lipid changes, gynecomastia and hot flashes.

Stéphane Thiroloix, Executive Vice President, Corporate Development of Ipsen, said: "We are very pleased with the results of this clinical trial, which confirm the efficacy and the good safety profile of toremifene citrate 80 mg. Subject to regulatory approval, this drug has the potential to address a significant unmet medical need by providing a new therapeutic approach to treat the side symptoms of androgen deprivation therapy. This product is an excellent fit with Ipsen’s existing Decapeptyl^® franchise, reinforcing our positioning in the treatment of hormone-dependent diseases and broadens the range of our prostate cancer related product portfolio."


About the study

In this large phase III study, 1389 ADT patients were randomized to evaluate the efficacy and safety of toremifene citrate 80 mg compared to placebo over two years in approximately 150 clinical sites in the United States and Mexico. All men enrolled were over 50 years or older with histologically documented prostate cancer, serum prostate specific antigen (PSA) 4 ng/ml or less and a history of orchiectomy, or treatment with GnRH agonist for at least 6 months or intermittent treatment with a GnRH agonist for at least 12 months. The primary endpoint of this study was reached with a significant reduction (p<0.05) in the incidence of morphometric vertebral fractures of at least 50% in the toremifene group as compared to the placebo group with a fracture rate of 2.5% vs 4.9% respectively (preliminary analysis). Furthermore, Bone Mineral Density (BMD) data have confirmed the anti-osteoporotic efficacy of toremifene citrate 80mg/day in significantly preventing bone loss (p<0.0001) at the spine as well as at the hip and femur level. Toremifene citrate 80 mg treatment compared to placebo also resulted in a decrease in total cholesterol (p=0.011), LDL (p=0.018), and triglycerides (p<0.0001), and an increase in HDL (p=0.001). In regard to the effect of toremifene citrate 80 mg on hot flashes, the evaluation of these data is still ongoing and will be reviewed with the final data set.

Tolerance of the treatment was good. Among the most common adverse events that occurred in over 2% of study subjects were arthralgia (treated 7.3%, placebo 11.8%), dizziness (treated 6.3%, placebo 5.0%), back pain (treated 5.9%, placebo 5.2%), and extremity pain (treated 5.0%, placebo 4.4%). There were 17 (2.4 %) venous thromboembolic events (VTE) in the toremifene citrate 80 mg treated group and 7 (1.02 %) in the placebo group. However the majority of VTE’s occurred in men with an high risk for a thromboembolic event including: age ><80 years, history of VTE, recent surgical procedure and immobilization.

About toremifene citrate 80 mg

Toremifene citrate 80 mg is a selective estrogen receptor modulator, or SERM, which GTx is developing as a daily tablet to treat the multiple estrogen related side effects of androgen deprivation therapy for advanced prostate cancer. Toremifene citrate was designed to bind to and selectively modulate estrogen receptors depending on the tissue type. GTx has rights to and plans to commercialize toremifene citrate 80 mg in the United States. GTx has licensed European rights to Ipsen Group, the leading marketer of ADT drugs in Europe.

About Ipsen

Ipsen is an innovation driven international specialty pharmaceutical group with over 20 products on the market and a total worldwide staff of nearly 4,000. The company’s development strategy is based on a combination of products in targeted therapeutic areas (oncology, endocrinology and neuromuscular disorders) which are growth drivers, and primary care products which contribute significantly to its research financing. This strategy is also supported by an active policy of partnerships. The location of its four Research and Development centres (Paris, Boston, Barcelona, London) gives the Group a competitive edge in gaining access to leading university research teams and highly qualified personnel. In 2006, R&D expenditure was €178.3 million, i.e. 20.7% of consolidated sales, which amounted to €861.7 million while total revenues amounted to €945.3 million (in IFRS). 700 people in R&D are dedicated to the discovery and development of innovative drugs for patient care. Ipsen’s shares are traded on Segment A of Eurolist by Euronext^TM (stock code: IPN, ISIN code: FR0010259150). Ipsen’s shares are eligible to the "Service de Regrave;glement Différé" ("SRD") and the Group is part of the SBF 120 index. For more information on Ipsen, visit our website at www.ipsen.com.

Ipsen Forward-Looking Statements

The forward-looking statements and targets contained herein are based on Ipsen's management's current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. Moreover, the Research and Development process involves several stages at each of which there is a substantial risk that the Group will fail to achieve its objectives and be forced to abandon its efforts in respect of a product in which it has invested significant sums. Thus, in order to develop a product which is viable from a commercial point of view, the Group must demonstrate, by means of pre-clinical and human clinical trials, that the molecules are effective and not dangerous to human beings. Therefore, the Group cannot be certain that favourable results obtained during pre-clinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the product concerned, or that the regulatory authorities will be satisfied with the data and the information provided by the Company. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen's business is subject to the risk factors outlined in its information documents filed with the French Autorité des marchés financiers.


Source: Ipsen

[Read more!]

EMEA recommends marketing authorisation of Ipsen’s Adenuric® (febuxostat) for the treatment of chronic hyperuricaemia in gout

Adenuric® represents the first major treatment of gout for more than forty years Paris (France), 21 February 2008 &mdash Ipsen (Euronext: FR0010259150; IPN) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) provided a positive opinion for Adenuric® (febuxostat) 80 mg and 120 mg tablets for the treatment of chronic hyperuricaemia in gout and recommended it for marketing authorisation. The CHMP recommendation will now be forwarded to the European Commission for final marketing approval, which typically occurs within 60 to 90 days. Following marketing approval, Adenuric® will become, since 1964, the first significant treatment alternative for chronic hyperuricaemia available to gout patients.

Adenuric^® is to be indicated for the treatment of chronic hyperuricaemia for conditions in which urate deposition has already occurred (including a history, or presence of, tophus and/or gouty arthritis). The detailed recommendations for the use of this product will be described in the Summary of Product Characteristics (SPC), to be made available after the medication receives marketing authorisation from the European Commission.

Once the product receives its marketing authorisation and its price is agreed, Febuxostat will be marketed by Ipsen in France under the brand name Adenuric^®. Outside France, the commercialisation of the product will be partnered.

Jean-Luc Bélingard, Chairman and Chief Executive Officer of Ipsen, said, "We are very proud to receive this positive opinion for Adenuric^® from the EMEA, and look forward to bringing this new molecule to market, pending European Commission approval. This innovative drug pioneers the first major treatment of gout for more than 40 years. It confirms Ipsen’s ability to continue to bring to the market important new treatment options for severely debilitating diseases."


About Adenuric^® (febuxostat)

Gout, a particularly painful type of arthritis, is the most frequent arthritis in men. It is caused by elevated levels of uric acid in the body: hyperuricaemia. Febuxostat, an oral, once-daily medication, is a novel nonpurine, selective inhibitor of xanthine oxidase studied for its effects on lowering levels of serum uric acid (sUA) in patients with gout. Febuxostat is licensed to Ipsen for Europe from Teijin Pharma Limited, Tokyo.

The EU submission includes two of the largest industry sponsored studies to date studying treatment of chronic gout patients. The goal of chronic gout treatment is per EULAR guidelines (European League Against Rheumatism) to reduce and maintain sUA levels below 6 mg/dL. Febuxostat demonstrated superior ability to lower and maintain in patients, serum uric acid at a level inferior to 6 mg/dl compared to conventionally used doses of allopurinol (febuxostat 80 and 120 mg: 51 &: 63 % resp. vs. allopurinol: 22%). In addition, one phase III study showed that gout patients with mild to moderate renal impairment (serum creatinine >1.5 - <2.0 mg/dl) had response rate of 44 and 45 % respectively with febuxostat 80 and 120 mg.

CHMP press release can be accessed at http:///www.emea.europa.eu.

In 2003, Ipsen entered into a Research and Development partnership with Teijin Pharma Limited, the core company of Teijin Group’s pharmaceutical and home healthcare business. The Teijin group is a Japanese industrial conglomerate specialising in the businesses of fibres, films, plastics and information technology (IT) as well as pharmaceuticals and home healthcare. This partnership covers the development and subsequent commercialisation of four of Ipsen’s products by Teijin Pharma in Japan and the development and marketing by Ipsen in Europe (i.e. European Union and Russia) of febuxostat, a product owned by Teijin Pharma and known as TMX-67.

About Ipsen

Ipsen is an innovation driven international specialty pharmaceutical group with over 20 products on the market and a total worldwide staff of nearly 4,000. The company’s development strategy is based on a combination of products in targeted therapeutic areas (oncology, endocrinology and neuromuscular disorders) which are growth drivers, and primary care products which contribute significantly to its research financing. This strategy is also supported by an active policy of partnerships. The location of its four Research and Development centres (Paris, Boston, Barcelona, London) gives the Group a competitive edge in gaining access to leading university research teams and highly qualified personnel. In 2006, R&D expenditure was €178.3 million, i.e. 20.7% of consolidated sales, which amounted to €861.7 million while total revenues amounted to €945.3 million (in IFRS). 700 people in R&D are dedicated to the discovery and development of innovative drugs for patient care. Ipsen’s shares are traded on Segment A of Eurolist by Euronext^TM (stock code: IPN, ISIN code: FR0010259150). Ipsen’s shares are eligible to the "Service de Regrave;glement Différé" ("SRD") and the Group is part of the SBF 120 index. For more information on Ipsen, visit our website at www.ipsen.com.

Ipsen Forward-Looking Statements

The forward-looking statements and targets contained herein are based on Ipsen's management's current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. Moreover, the Research and Development process involves several stages at each of which there is a substantial risk that the Group will fail to achieve its objectives and be forced to abandon its efforts in respect of a product in which it has invested significant sums. Thus, in order to develop a product which is viable from a commercial point of view, the Group must demonstrate, by means of pre-clinical and human clinical trials, that the molecules are effective and not dangerous to human beings. Therefore, the Group cannot be certain that favourable results obtained during pre-clinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the product concerned, or that the regulatory authorities will be satisfied with the data and the information provided by the Company. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen's business is subject to the risk factors outlined in its information documents filed with the French Autorité des marchés financiers.


Source: Ipsen

[Read more!]

Clinical update for Decapeptyl® 6-month formulation in advanced prostate cancer

Presentation of efficacy and safety Phase III results by Ipsen’s partner, Debiopharm, at the 9th International Symposium on GnRH in Berlin (Germany)

Paris (France), 12 February 2008 — Ipsen (Euronext: FR0010259150; IPN) announced that its partner Debiopharm presented today the results of a phase III study with its new 6-month formulation of Decapeptyl^®1, a luteinizing hormone releasing hormone agonist (LHRHa) for the treatment of advanced prostate cancer. The results presented show similar efficacy and safety to the already marketed 1- and 3-month formulations of triptorelin.

This multicenter, open, non-comparative, phase III study on the efficacy and safety of two consecutive injections at a six-month interval of triptorelin 6-month formulation in 120 patients with advanced prostate cancer, showed that 97.5% of patients achieved castrate levels of serum testosterone 28 days after the first injection and that 93% of the patients maintained serum testosterone levels below castrate level (defined as < 1.735 nmol/L or 50 ng/dL) from week 8 to 48. These efficacy and safety results are similar to those obtained previously with repeated administrations of the 1- and 3-month formulations of triptorelin in previous studies. Furthermore, local tolerance is good with only 6.7% of the patients treated reporting spontaneously site injection adverse events.

On 31 October 2007, Ipsen exclusively in-licensed from Debiopharm know-how and new patent applications for the commercialization rights of Decapeptyl^® (triptorelin pamoate) in the world excluding North America, and some other countries (Sweden, Israel, Iran and Japan).

¹Triptorelin formulations are mainly sold as Decapeptyl^®, Diphereline^® and Pamorelin^®

About Decapeptyl^®

Decapeptyl^® is a peptide formulation for injection that was initially developed by Debiopharm and continues to be used mainly in the treatment of advanced metastatic prostate cancer. Additional indications developed subsequently include the treatment of uterine fibroids (a benign tumour of muscle tissues in the uterus), endometriosis (proliferation of endometrial tissue, the mucous membrane that lines the uterine wall outside the reproductive tract) prior to surgery or when surgery is not deemed appropriate, as well as early onset puberty and female infertility (in vitro fertilisation). Decapeptyl^® is available in monthly or quarterly sustained-release formulations, as well as a daily formulation. The active substance in Decapeptyl^® is triptorelin, a decapeptide analogue of GnRH (Gonadotrophin Releasing Hormone), a hormone secreted by the hypothalamus, which initially stimulates the release of pituitary gonadotrophins (hormones produced by the pituitary gland), which in turn control hormonal secretions by the testes and ovaries. Decapeptyl^® was initially launched in France during 1986. At 31 December 2007, Decapeptyl^® had marketing authorizations in over 60 countries, including 25 in Europe. In 2007, 59.7% of Decapeptyl^® sales were generated in the five major European Countries, and reached a total of 235.1M€.

Debiopharm, which holds the patent to pamoate formulations of Decapeptyl^® has granted Ipsen an exclusive licence to Decapeptyl^® within the European Union (outside Sweden) and in certain other countries. Debiopharm has also granted Ipsen a co-exclusive licence to manufacture Decapeptyl^® within the European Union (outside Sweden) and in certain other countries (with Debiopharm nonetheless retaining the right to manufacture and supply Decapeptyl^® for its own purposes and those of its otherDecapeptyl^® licensees in territories not licensed to the Group).

About Ipsen

Ipsen is an innovation driven international specialty pharmaceutical group with over 20 products on the market and a total worldwide staff of nearly 4,000. The company’s development strategy is based on a combination of products in targeted therapeutic areas (oncology, endocrinology and neuromuscular disorders) which are growth drivers, and primary care products which contribute significantly to its research financing. This strategy is also supported by an active policy of partnerships. The location of its four Research and Development centres (Paris, Boston, Barcelona, London) gives the Group a competitive edge in gaining access to leading university research teams and highly qualified personnel. In 2006, R&D expenditure was €178.3 million, i.e. 20.7% of consolidated sales, which amounted to €861.7 million while total revenues amounted to €945.3 million (in IFRS). 700 people in R&D are dedicated to the discovery and development of innovative drugs for patient care. Ipsen’s shares are traded on Segment A of Eurolist by Euronext^TM (stock code: IPN, ISIN code: FR0010259150). Ipsen’s shares are eligible to the "Service de Regrave;glement Différé" ("SRD") and the Group is part of the SBF 120 index. For more information on Ipsen, visit our website at www.ipsen.com.

Forward-Looking Statements

The forward-looking statements and targets contained herein are based on Ipsen's management's current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. Moreover, the Research and Development process involves several stages at each of which there is a substantial risk that the Group will fail to achieve its objectives and be forced to abandon its efforts in respect of a product in which it has invested significant sums. Thus, in order to develop a product which is viable from a commercial point of view, the Group must demonstrate, by means of pre-clinical and human clinical trials, that the molecules are effective and not dangerous to human beings. Therefore, the Group cannot be certain that favourable results obtained during pre-clinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the product concerned, or that the regulatory authorities will be satisfied with the data and the information provided by the Company. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen's business is subject to the risk factors outlined in its information documents filed with the French Autorité des marchés financiers.


Source: Ipsen

[Read more!]

Polyplus-transfection has produced the first GMP-quality clinical batch of its nucleic acid transfer reagent

Polyplus-transfection will deliver GMP-compliant in vivo-jetPEI for a Phase II clinical trial Strasbourg, February 1st 2008 — Polyplus-transfection, a company specialized in the research, development and marketing of innovative reagents for transfection and RNA interference (RNAi), announces today the production of the first batch of its transfection reagent in vivo-jetPEI manufactured in full compliance with Good Manufacturing Practice (GMP). This GMP-compliant in vivo-jetPEI is required for clinical trials involving nucleic acids delivery (DNA and siRNA).

Polyplus-transfection carried out preliminary work to transfer production to GMP-compliance in 2007 thanks to financial support from the AFM, France's Muscular Dystrophy Association. This has made it possible for a Phase II clinical trial to start in the field of cancer therapy this year using Polyplus' GMP-compliant in vivo-jetPEI. Details of the clinical trial have not yet been disclosed.

Polyplus-transfection offers its customers the possibility of using the same transfection reagent from the early stages of preclinical research to clinical trials in humans. The in vivo-jetPEI molecule is able to transfect effectively both in vitro and in vivo — which is not the case with most of the commercially available transfection reagents.

A Drug Master File (DMF) describing the manufacturing of in vivo-jetPEI has been filed with the United States Food and Drug Administration (FDA). The DMF provides confidential detailed information about the manufacturing process of the reagent, thus simplifying the FDA documentation required for clinical trial applications. "We are proud to have delivered this first GMP-compliant batch of in vivo-jetPEI and to have completed the production process transfer," said Joëlle Bloch, CEO of Polyplus-transfection. "The GMP-compliant availability of our leading product for human clinical use is a crucial advantage in the choice of a transfection agent for therapeutic projects. It will speed up the growth of all Polyplus' in vivo transfection agents." And she added: "We are eagerly awaiting the beginning of this Phase II clinical trial using in vivo-jetPEI that is scheduled for 2008 in the field of anti-cancer therapy."

The development of the in vivo-jetPEI GMP-compliant process has required the design of new quality control tests to meet the current requirements in the US and the EU.


About Polyplus-transfection

Polyplus-transfection is focused on developing innovative solutions for intracellular delivery of nucleic acids. The company has been marketing its transfection reagents worldwide since 2001 and is reinvesting most of its revenues into research and development. Transfection consists in introducing a gene or a small interfering RNA into cells. This technique makes it possible to cross the cellular barriers and deliver such biomolecules into the cell for research or therapeutic purposes.

Customers of Polyplus-transfection's products and services include biotechnology and pharmaceutical companies as well as life science academic laboratories. Polyplus-transfection offers high quality consultancy, personalized scientific support and expertise in regulatory affairs related to the use of its reagents in clinical trials. Phases I/II cancer gene therapy and AIDS trials are underway in Israel, USA, Sweden and Germany using GMP-compliant reagents from Polyplus-transfection.

Polyplus-transfection R&D has well-established partnerships with biotech companies and is also involved in several European research collaboration networks, such as GIANT (Gene Therapy, an Integrated Approach to Neoplastic Treatment) and RIGHT (RNA Interference Technology as Human Therapeutic Tool). The company also drives the OligoPlus research program for the "Therapeutic Innovations" Competitiveness Cluster, focusing on new tools for diagnostic.

The Strasbourg-based company is recognized as a leading innovator in the transfection market, with ISO 9001:2000 certification, three exclusive licenses from the CNRS and numerous patent filed.

For more information, visit: http://www.polyplus-transfection.com


Source: Polyplus-transfection

[Read more!]