Ipsen (ParisIPN), announced preliminary results from a Phase II openlabel clinical trial (MS316 study) that evaluates the coadministration of recombinant human growth hormone (rhGH) and recombinant human insulinlike growth factor1 (rhIGF1) in two separate daily injections as a potential treatment for children with otherwise unexplained short stature associated with low IGF1 levels. Ipsen also announced results from a longterm study of rhIGF1 (study 1419) in patients with severe primary insulinlike growth factor deficiency (sPIGFD) that demonstrated that longterm twicedaily therapy with rhIGF1 improved the adult and near adult heights of extremely short patients with sPIGFD. The data from these two studies were presented along with posters on rhIGF1 (Increlex®, mecasermin [rDNA origin] injection) at the 8th Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society / European Society for Pediatric Endocrinology (LWPES/ESPE) in New York, NY.

These studies were performed under INDs (investigational new drug application protocols) and the coadministration of rhGH and rhIGF1 is not an approved administration regimen for Increlex®. At this point in time, Increlex® is marketed in the U.S. and other countries throughout the world for the treatment of growth failure in children with severe Primary IGFD using twicedaily injections.

“The structuring of its US platform in 2008 enabled Ipsen to build a fully fledged commercial presence in the US but also to gain access to a promising pipeline. The Group intends to capitalize on its unique growth disorders and endocrinology franchise. The interim data presented at the LWPES/ ESPE meeting validate ongoing investigations and we look forward to continuing our research progress with our partners on this effort,” said JeanLuc Bélingard, Chairman and Chief Executive Officer, Ipsen. “Ipsen Group remains fully committed to furthering its endocrinology research and product development in support to its fastest growing franchise in this highlyspecialized therapeutic area.”

The MS316 study is an ongoing Phase II, randomized, openlabel, activetreatment controlled trial evaluating the efficacy and safety of the coadministration of rhGH and rhIGF1 therapy versus rhGH alone in 106 children with short stature associated with low levels of IGF1. All participants received morning injections of either rhGH alone (45 μg/kg oncedaily) or coadministered with rhIGF1 (45 μg/kg rhGH and 50, 100 or 150 μg/kg rhIGF1 also once daily as two injections). Subjects had a baseline mean height standard deviation score (SDS) of 2.5. Thirtysix of the children enrolled in the study have completed one year of treatment. Firstyear height velocities were 9.2 cm for the patients receiving rhGH alone and 10.4, 10.7, and 12.1cm for the three rhGH/rhIGF1 groups. At the end of one year, changes in mean height SDS were 0.72 for the patients receiving rhGH alone and 0.88, 0.91, and 1.11 for the three rhGH/rhIGF1 groups. Among all patients, the most common adverse events (> 15%) were headache, upper respiratory infection, injection site reactions and fever. Other noteworthy but less frequent adverse events included vomiting, hypoglycemia and gynecomastia. In addition, 2 transient cases of papilledema (probable intracranial hypertension) occurred with coadministration. In both cases, treatment was discontinued and restarted without recurrence.

“The preliminary results for the MS316 study of a coadministration treatment of recombinant IGF1 and recombinant growth hormone in children with short stature associated with low IGF1 are encouraging,” said L. Kurt Midyett, MD, Medical Director, Childrens Mercy Hospital and Clinics, Kansas City, Missouri. “While there is a compelling scientific rationale for coadministration therapy, this remains a research endeavor at this point and I look forward to seeing the completed data compiled and analyzed for this potential coadministration treatment option.”

Ipsen also announced data on 16 patients with severe Primary IGFD treated with Increlex® until adult or nearadult height. These patients were part of the original registration trial for Increlex® (study 1419), which continues to collect longterm followup data on treatment until they reached adult height. The analysis was done with 9 male and 7 female patients. Patients received a mean dose of 112 μg/kg Increlex® twicedaily for a mean of 9.9 years. Five patients also received GnRHanalog. The mean estimated gain in height up to the time of nearadult height in patients taking Increlex® was 13.2 cm (range 0.4 to 23.4) and the mean estimated gain in adult height was conservatively estimated as 10.5 cm (range 2.9 to 22.3). While longterm Increlex® therapy improved adult height for extremely short patients with severe Primary IGFD, most patients did not experience enough catchup growth to bring their heights into the normal adult range. The most common side effects associated with Increlex® include dizziness, headache, nausea and vomiting.

“The data supporting the efficacy and safety of recombinant human IGFI (rhIGFI) (Increlex®) continue to grow, and these results demonstrate that children with severe Primary IGFI deficiency can improve their adult/near adult height with longterm IGFI therapy,” said Philippe F. Backeljauw, MD, Professor of Pediatrics, Cincinnati Childrens Hospital Medical Center. “These results provide increased confidence to treat patients with severe Primary IGFD with rhIGFI (Increlex®).”

Other Ipsen poster presentations included safety and efficacy data of Increlex® based on the IGFD Registry database, which now has over 700 patients enrolled since May 2006, and data on an 86week, openlabel trial of pharmacokinetic (PK)based oncedaily (QD) dosing of rhIGF1 in 45 treatmentnaïve prepubertal children with short stature associated with low IGF1 levels.

About Increlex® (mecasermin (rDNA origin) injection)

The active ingredient of Increlex® is recombinant human insulinlike growth factor1 (IGF1). IGF1 is the direct mediator of many of growth hormones (GH) effects on statural growth, and must be present for normal growth of bones and cartilage in children. Without adequate IGF1, children may not achieve normal height.

Increlex® has been marketed in the United States since early 2006 and in Europe since late 2007 for the treatment of growth failure in children with severe Primary IGFD. Severe Primary IGFD is defined by height at least three standard deviations below the mean and IGF1 levels at least three standard deviations below the mean for age and sex, and presence of normal or elevated GH level in the US, and IGF1 levels below the 2.5% percentile for age and sex, and GH sufficiency throughout Europe. In children with this disorder, low IGF1 levels may be due to growthhormone resistance or insensitivity associated with mutations in GH receptors, postGH receptor signaling pathways, or to defects in the IGF1 gene.

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