With near-term plans mapped out for approval of its lead product, Insmed Inc. began a pivotal Phase III trial of its late-stage hormone replacement therapy in children with growth hormone insensitivity syndrome (GHIS).

The study is designed to measure rhIGF-I/rhIGFBP-3's effect on an increase in height velocity in patients with the genetic disorder, which causes them to fail to produce insulin-like growth factor-I (IGF-I). The product combines IGF-I, a protein integral to the actions of both insulin and growth hormone, with a secondary protein called binding protein-3 (BP-3), to which IGF-I binds and circulates throughout the human body in tandem.

Richmond, Va.-based Insmed said data generated from the 30-patient trial, combined with findings acquired last fall from Peapack, N.J.-based Pharmacia Corp. related to its prior European regulatory filings in GHIS, would be used to support marketing applications next year.

"It involves a small number of patients, and we hope to have the primary efficacy data collected by the first half of 2004," Insmed President and CEO Geoffrey Allan told an audience at the BIO 2003 convention in a presentation also broadcast via the Internet. "That puts us in a position to file for product registration in the U.S. and in Europe in the second half of 2004."

Just last week, Insmed released data at the Endocrine Society meeting in Philadelphia showing that a single daily dose of rhIGF-I/rhIGFBP-3, previously referred to as SomatoKine, safely normalized serum levels of IGF-I in children with GHIS. There were no adverse events reported in the trial, which also revealed that a single dose of rhIGF-I/rhIGFBP-3 provided the same drug exposure as two daily injections of unbound IGF-I. Pharmacia's data showed that treatment with its unbound IGF-I product produced 3 cm to 8 cm of growth over a period of a year, compared to 1 cm per year among untreated patients.

Allan said the plan produces Insmed's best near-term commercial opportunity, with approval expected within 18 months for a well-defined niche market. The company has received orphan drug designation in the U.S. and Europe, providing seven and 10 years of market exclusivity, respectively, upon approval in that indication.

"We believe that the long-term commercial growth for this product can be developed through further clinical trials that warrant expansion in indications where we have already established proof of concept - namely diabetes, bone injury and osteoporotic hip fracture repair," he added.

In April, Insmed began a named-patient program in Europe to make rhIGF-I/rhIGFBP-3 available to the young patient population.

Deeper in its pipeline, Insmed has established preclinical proof of efficacy of another hormone replacement therapy for cancer. Allan said the company has shown that its IGFBP-3 product induces apoptosis and inhibits the growth of cancer cells in preclinical models of lung, colon and breast cancer.

"Our contention is that there are a number of disease conditions where there is a deficiency in either the primary bioactive peptide, IGF-I, or its binding protein, BP-3," he said. Allan added that Insmed, which reported a cash standing of about $25 million at the end of its most recent fiscal quarter, planned to push the product into clinical trials in the next six months and look to outlicense its rights to an oncology partner.

That product continues to move forward as a key spoke in Insmed's development wheel, which was deflated late last summer when the company dropped its INS-1 product after the candidate failed to achieve statistical significance on its primary efficacy measures in a Phase II study in Type II diabetes and polycystic ovary syndrome patients. (See BioWorld Today, Sept. 11, 2002.)

Insmed's stock (NASDAQ:INSM) gained 29 cents Monday to close at $2.70.