FDA Approves Efficacy Results for Spine Bone Mineral Density in Childhood-Onset Growth Hormone Deficient Adults.

SOUTH SAN FRANCISCO, Calif.--(BW HealthWire)--Dec. 2, 1999--

Genentech, Inc. (NYSE: DNA) today announced approval from the U.S. Food and Drug Administration (FDA) of additional efficacy results for its growth hormone products -- Nutropin(R) (somatropin (rDNA origin) for injection) and Nutropin AQ(R) (somatropin (rDNA origin) injection) -- on the effects of growth hormone replacement therapy on spine bone mineral density in young adults with childhood-onset growth hormone deficiency (GHD).

New clinical data show significant increases in spine bone mineral density can be achieved with growth hormone therapy in these growth hormone (GH) deficient young adults, who often have low bone mineral density an indicator that bones may be fragile and more susceptible to fractures.

Reduced bone mineral density -- a measure of bone mass -- is identified frequently as part of adult GHD, occurring more commonly in adults who were deficient as children (childhood-onset GHD) than in those who became deficient as adults (adult-onset GHD). In a recently completed randomized, two-year, placebo-controlled clinical trial of its recombinant growth hormone, Genentech found in young adults with childhood-onset GHD, Nutropin significantly increased the bone mineral density at the spine -- an area at risk for fractures in patients with low bone mineral density.

There were no significant improvements in total bone mineral density when compared to placebo. The percent change from baseline in spine bone mineral density for patients in the childhood-onset adult GHD study after up to 24 months of treatment was 1.0 percent for the placebo group and 4.6 percent for the higher-dose, Nutropin treated group (25 micrograms/kg/day). Thirty-five percent of patients treated with this dose had elevated levels of IGF-I at some point during the study, which may carry unknown risks. A lower dose (12.5 micrograms/kg/day) did not show significant increases in bone mineral density compared to placebo. Additionally, a trial of adult-onset GH deficient patients showed no statistically significant effects on bone mineral density where patients received 12.5 micrograms/kg/day for one year.

"In addition to its role in lengthening bones to increase stature, growth hormone also contributes to the maintenance of bone mineral in adults," said Dr. Louis Underwood, Professor of Pediatrics, University of North Carolina School of Medicine. "These data tell us that reaching adult height should be considered only a check point rather than an end point in the treatment of patients with growth hormone deficiency."

"These findings regarding the effects of growth hormone replacement therapy on bone density are critical information for physicians and patients," said Stephen Dilly, M.D., Ph.D., vice president, Medical Affairs at Genentech. "We hope that these clinical results will help inform the endocrine community of the role of continued growth hormone therapy for young adults with growth hormone deficiency."

Despite previous growth hormone therapy in childhood and a relatively young mean age of 24 years in the study, more than half of participants in this study at baseline were osteopenic -- a condition in which bones have reduced density. Further, some of the patients already had evidence of osteoporosis, characterized by low bone density and deterioration of bone tissue that can lead to increased risk of fracture, especially of the hip, spine and wrist. For spine bone mineral density in childhood-onset growth hormone deficient patients, 55 percent had a spine bone mineral density score below -1 at baseline, which is the World Health Organization (WHO) definition for osteopenia, and of these, 14 percent were below -2.5, the WHO's definition for osteoporosis.

The most common side effects reported by GH deficient adults treated with Nutropin were dose related and included edema (or swelling) and joint pain, and rare carpal tunnel syndrome. In GH deficient adults, Nutropin was associated with an increase of insulin levels; therefore, patients with diabetes should be monitored closely. Nutropin should not be used in patients with active tumors. Growth hormone also should not be initiated to treat patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or to patients having acute respiratory failure. Experience with prolonged GH treatment in adults is limited.

There is a critical period during an individual's teens and early 20's when peak bone mass normally is reached; after this time, people tend to have a net loss of bone, which over time, may place certain individuals at risk for osteoporosis. Throughout life, bones constantly are undergoing a cycle of remodeling, with old bone being removed and new bone created in its place. These data suggest that accruing and maintaining bone mass may be another compelling reason for continuing growth hormone therapy in GH deficient adults.

In December 1997, Genentech's lyophilized Nutropin and Nutropin AQ, the first liquid (aqueous) recombinant human growth hormone product, received FDA approval for the replacement of endogenous growth hormone in patients with adult GHD who meet specific criteria. This includes a diagnosis of GHD by means of a subnormal response to a standard growth hormone stimulation test as well as having adult GHD due to pituitary disease, tumor or trauma, or from childhood onset of the condition.

Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Twelve of the approved products of biotechnology stem from Genentech science. Genentech markets seven products directly in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange under the symbol DNA.