New diagnostic tools and safety studies provide further evidence supporting rhIGF-1 as a potential therapy for short stature due to primary IGF-1 deficiency
San Diego, CA – June 6, 2005 – Tercica, Inc. (Nasdaq: TRCA) announced today that it presented data from several studies in poster sessions at the 87th Annual Meeting of the Endocrine Society. Some of these data are included in the company's New Drug Application (NDA) for recombinant human Insulin-like Growth Factor-1 (rhIGF-1) for the treatment of short stature caused by primary IGF-1 deficiency (Primary IGFD). The NDA was accepted for priority review by the FDA on April 29.
Data presented include: results from a human pharmacokinetic study; results from a novel diagnostic test used to distinguish children who may be insensitive to the effects of growth hormone and therefore who likely have growth failure due to primary insulin-like growth factor-1 (IGF-1) deficiency (Primary IGFD). The company also presented human and animal safety data showing no evidence of immunotoxic effects with long-term rhIGF-1 treatment; and a life-time rhIGF-1 toxicology study in animals that demonstrated a reduction in the incidence of some endocrine cancers. These data provide further insight into the long-term safety of rhIGF-1 treatment.
"These pharmacokinetic and safety studies indicate the depth of data included in our New Drug Application and further strengthen our confidence in Increlex as a safe replacement therapy for children with short stature caused by Primary IGFD," said Ross Clark, Ph.D., Tercica's Founder and Chief Technical Officer.
A New Treatment Allocation Tool
Results were presented from a human pharmacokinetic study analyzed using an IGF-1 population pharmacokinetic (POP-PK) model which showed that a child's blood IGF-1 level is largely determined by their blood level of insulinlike growth factor binding protein-3 (IGFBP-3). The model can be used to guide rhIGF-1 dosing in order to better normalize a child's blood IGF-1 level.
A second study described a new test, the IGF-1 Production Test, which uses data generated from the POP-PK model to estimate the amount of IGF-1 produced by a child before and after growth hormone therapy to provide a better measure of growth hormone sensitivity.
"With the development of our POP-PK model, we have greater understanding of IGF-1 pharmacokinetics and can more accurately anticipate the blood IGF- 1 levels that will occur after Increlex administration, enabling us to potentially improve upon the traditional measures used to test for growth hormone insensitivity," said George Bright, M.D., Vice President and Medical Director, Endocrinology at Tercica. "We believe the IGF-1 Production Test will enable physicians to differentiate between children who would respond to -- and those who would be insensitive to -- the effects of growth hormone, allowing for more accurate diagnosis and treatment allocation for children with short stature."
The POP-PK model was developed from rhIGF-1 pharmacokinetic data generated in 36 patients who ranged from severely IGFD to normal. The model was then tested by predicting the blood IGF-1 levels after rhIGF-1 dosing in a further 18 IGFD subjects. Across a wide range of IGFBP-3 levels and IGF-1 doses, IGF-1 clearance was almost completely dependent on blood IGFBP-3 levels (r2 = 0.87). Researchers used this tight relationship to estimate the IGF-1 production rate. The IGF-1 production rate in patients with severe IGFD averaged 0.95 ug/kg/h compared to 2.81 ug/kg/h in normal patients. The lack of production rate overlap between the groups suggests it will be possible to establish IGFD on the basis of IGF-1 production rather than blood IGF-1 concentrations.
Toxicology and Antibody Studies Reinforce the Safety Profile of Increlex
A long-term study in 22 children with Primary IGFD assessed the effect of long-term rhIGF-1 treatment on the generation of anti-IGF-1 antibodies. Antibodies found were generally of low titer; in addition, antibodies that were detected did not increase in titer during the two-year study. The researchers segregated the children into those with and those without antibodies and found no statistical significance in the growth response to rhIGF-1 between the two groups. Therefore, in these children, any antibodies generated did not seem to affect the growth response to rhIGF-1 or present any safety concerns. In other children, therapy has been maintained for up to 11.5 years with no evidence of immunotoxicity.
A placebo-controlled lifetime carcinogenicity study was performed in 900 rats treated with placebo or four doses of rhIGF-1 for up to two years.
Researchers observed that rhIGF-1 treatment resulted in dose-related reductions in the incidence of selected endocrine cancers. In addition to supporting the safety profile of rhIGF-1 treatment, these findings also suggest that epidemiological relationships between blood IGF-1 levels and the risk of endocrine cancers in humans should be investigated.
"These studies add to our extensive portfolio of safety data, were submitted as part of our NDA, and give us a high confidence level in the long-term safety of rhIGF-1 therapy" said Dr. Clark. "We are pleased to be able to provide the endocrine community with the only published long-term carcinogenicity and antibody studies as part of our ongoing commitment to ensure the safety of rhIGF-1 replacement therapy."
About IGF-1 and Primary IGFD
Insulin-like Growth Factor-1 (IGF-1) is the principal hormone necessary for statural growth. IGF-1 is released in response to stimulation by growth hormone. Primary IGFD is diagnosed in children who have normal or elevated secretion of endogenous growth hormone and whose height and serum IGF-1 levels are more than two standard deviations below the mean. A sub-set of these children, whose height and serum IGF-1 levels are more than three standard deviations below the mean, are diagnosed with Severe Primary IGFD. Primary IGFD afflicts an estimated 30,000 children evaluated for short stature in the United States. Approximately 6,000 children suffer from Severe Primary IGFD and could become eligible for Increlex therapy if approved by the FDA.
Tercica, Inc. is a biopharmaceutical company focused on the development and commercialization of products to improve endocrine health. The company's first product candidate, Increlex
TM(mecasermin [rDNA origin] injection), or recombinant human insulin-like growth factor-1 (rhIGF-1), is being developed for the treatment of short stature and associated metabolic disorders. For further information on Tercica, please visit www.tercica.com.
Safe Harbor Statement
Except for the historical statements contained herein, this press release contains forward-looking statements, including without limitation the following: (A) that the pharmacokinetic and safety studies strengthen Tercica's confidence in Increlex as a safe replacement therapy for children with short stature caused by Primary IGFD; (B) that Primary IGFD afflicts an estimated 30,000 children evaluated for short stature in the United States; and (C) that approximately 6,000 children suffer from Severe Primary IGFD and could become eligible for Increlex
TMtherapy if approved by the FDA. Because Tercica's forward-looking statements are subject to risks and uncertainties, there are important factors that could cause actual results to differ materially from those in the forward-looking statements. These factors include without limitation: (1) those risks and uncertainties disclosed from time to time in reports filed by Tercica with the SEC, most recently Tercica's Form 10-Q filed on May 16, 2005 and Form 8-K filing on May 19, 2005; (2) the results from the studies may not extrapolate to the larger patient population; (3) Tercica's estimates might not accurately reflect the number of children afflicted with Primary IGFD and Severe Primary IGFD; and (4) that there would be no product launch if the FDA does not grant Tercica marketing approval, grants Tercica marketing approval covering so few patients that it is not commercially reasonable for the Company to launch, or grants Insmed Incorporated's product marketing exclusivity under the Orphan Drug Act that would block Tercica from being able to market or sell its product. These statements are based on information as of the date hereof, and the Company assumes no obligation to update any forwardlooking statement.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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