Tercica presents two pharmacokinetic studies in an oral session at Endocrine Society Meeting

06/07/05

Human studies demonstrate that administration of rhIGF-1 alone causes a prompt increase in blood IGFBP-3 levels

SAN DIEGO, June 7 /PRNewswire-FirstCall/ -- Tercica, Inc. (Nasdaq: TRCA) announced today that it presented data from two large pharmacokinetic studies today in an oral session at the 87th Annual Meeting of the Endocrine Society. The studies demonstrate that following a dose of recombinant human insulin-like growth factor-1 (rhIGF-1), there is a prompt increase in serum insulin-like growth factor binding protein-3 (IGFBP-3). Preliminary observations of this effect were included in the company's New Drug Application (NDA) for Increlex(TM) (mecasermin [rDNA origin] injection), or rhIGF-1, which was accepted for filing and granted priority review by the U.S. Food and Drug Administration on April 29.

"We designed these studies to determine the rhIGF-1 dosing necessary to normalize IGF-1 levels in IGFD children and to understand how rhIGF-1 dosing affects the relationship between the body's IGF-1 and IGFBP-3 levels," said George Bright, M.D., Tercica's Vice President and Medical Director, Endocrinology. "These findings are significant, as they reveal that irrespective of a child's IGFBP-3 status, or the degree of IGF-1 deficiency, IGFBP-3 levels increase in the blood immediately following a dose of rhIGF-1. These increased IGFBP-3 levels may increase the stability of IGF-1 in the bloodstream, which may help guide the optimal dosing of rhIGF-1 to achieve physiologic IGF-1 replacement, and in turn, optimal growth."

The pharmacokinetic studies were designed to study rhIGF-1 dosing in patients with IGF-1 deficiency (IGFD), and its effect on serum IGF-1 and IGFBP-3 levels. The first single-dose, 36-hour study observed 36 patients (12 patients per group) with either severe IGFD, moderate IGFD, or who were IGF-1 sufficient. The patients were randomized to receive a single subcutaneous injection of rhIGF-1. A second chronic-dosing study was performed in 27 patients with moderate IGFD who received multiple subcutaneous injections of rhIGF-1, with once- or twice-daily dosing, for three weeks.

After chronic dosing, although basal IGFBP-3 levels, as expected, fell, there was still a prompt increase in serum IGFBP-3 levels after each IGF-1 injection. The 63 patients -- ranging in age from 9 to 54 years -- showed consistent post-dose increases in mean +/- serum IGF-1 (200 +/- 86%) and IGFBP-3 (32 +/- 21%). The prompt and dose-related rise in IGFBP-3, synchronized to the rise in IGF-1 levels, suggests that IGFBP-3 is not newly synthesized; rather, it is likely recruited into the blood, and/or IGF-1 is stabilized in serum by its binding to IGFBP-3.

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.

Source: Eurekalert & others

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