IPSEN: Increlex® Receives Marketing Authorisation in the European Union

Business Wire, August 9, 2007

PARIS -- Regulatory News:

Increlex([R]) is the First Recombinant Human Insulin-Like Growth Factor-1 Therapy Approved in Europe for Severe Primary Igf-1 Deficiency

Ipsen (Paris:IPN) today announced that the European Commission granted marketing authorisation for Increlex([R]) (mecasermin) 10 mg/ml solution for injection in the European Union.

The indication approved is for the long-term treatment of growth failure in children and adolescents with severe primary insulin-like growth factor-1 deficiency (severe primary IGFD).

Increlex([R]) was designated as an orphan medicinal product in the European Union on 22 May 2006. The European marketing authorisation provides Increlex([R])a ten-year marketing exclusivity for the treatment of severe Primary IGFD.

In October 2006, Tercica Inc. granted Ipsen the development and commercialisation rights for Increlex([R]) in Europe and certain other territories; Ipsen is now in the process of launching this drug from October 2007 in the European Union. According to the terms of the agreement, the approval of Increlex([R]) marketing authorisation in the European Union triggers a EU15 million (approximately US$20 million) milestone payment by Ipsen to Tercica.

"The effect of growth hormone (GH) is to a major part mediated by insulin-like growth-factor-1 (IGF-1). If the biochemical steps leading to the formation of IGF-I are interrupted then patients are suffering from primary IGF-1 deficiency and cannot respond to GH therapy. Replacement with IGF-1 is the pathogenetically appropriate therapy in these instances" said Professor Dr. Michael B. Ranke, Paediatric Endocrinology Section, University Children's Hospital, University of Tuebingen, Germany. "Increlex([R]) (mecasernim), a recombinant human insulin-like growth factor-1 (IGF-1) thus opens a new field for the treatment of previously untreatable children with severely short stature."

Christophe Jean, Executive Vice-President and Chief Operating Officer of Ipsen, and Board member of Tercica Inc., said "We are very pleased that Increlex([R]) will be soon available to patients and physicians for the treatment of growth failure in children and adolescents with severe primary IGF-1 deficiency. Increlex([R]) fits perfectly in our existing global endocrinology franchise, along with Somatuline([R]) and NutropinAq([R]) to provide endocrinologists with a comprehensive solution for the treatment of patients suffering from growth disorders."

About the marketing authorisation

(The European Public Assessment Report (EPAR) summary can be accessed at www.emea.europa.eu)

This decision follows the filing by Tercica Inc., Ipsen's partner, of an application for marketing authorisation for Increlex([R]) in the European Union in December 2005. The positive opinion, recommending to grant a marketing authorisation under exceptional circumstances for Increlex([R]), was adopted by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) on 24 May 2007. Such authorisations are permissible for medicinal products for which the applicant can demonstrate that comprehensive data cannot be provided, for example because of the rarity of the condition, as long as it can be demonstrated on a regular basis that the benefits outweigh the risks. Every year, Ipsen and Tercica will review with the EMEA any new information that may become available.

The positive decision of the EMEA is based on clinical data from 76 patients who were treated with Increlex([R]) for up to 12.5 years. The primary endpoint in the pivotal clinical study was height velocity, which increased from an average of 2.8 cm per year at baseline to an average of 8.0 cm per year (p< 0.0001) in the first year of treatment and 5.8 cm in the second. The growth rate stabilised at around 4.7 cm per year from the fourth year of treatment.

About Increlex([R])

Mechanism of action

The active ingredient of Increlex([R]) is recombinant human insulin-like growth factor-1 (IGF-1). IGF-1 is the direct mediator of growth hormone's effect on statural growth, and must be present for normal growth of bones and cartilage in children. In severe primary IGFD, children's' serum IGF-1 levels are low, despite the presence of normal or elevated GH level. Without adequate IGF-1, children cannot achieve normal height. In children with this disorder, low IGF-1 levels are due to growth hormone resistance associated with mutations in GH receptors, post-GH receptor signalling pathways, or to defects in IGF-1 gene expression. As such, these children cannot be expected to respond adequately to exogenous GH treatment. Some individuals may also have a range of metabolic disorders, including lipid abnormalities, decreased bone density, obesity and insulin resistance.

Indication

The summary of product characteristics defines severe Primary IGFD as:

* a height standard deviation score (<=) -3.0,

* basal IGF-1 levels below the 2.5th percentile for age and gender,

* GH sufficiency, and

* the exclusion of secondary forms of IGF-1 deficiency, such as malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory steroids.