Extended treatment with active ingredient increases bone volume and calcium content

Jan 13 2010

Genta Incorporated (OTCBB: GETA) today announced publication of two scientific studies that test the active ingredient in Genta’s program to develop orally available gallium-containing compounds and the Company’s marketed product, Ganite^® (gallium nitrate for injection). In these studies, a compound containing the active ingredient was tested in a widely accepted animal model of established osteoporosis. The new data show that extended treatment with the active ingredient significantly increased bone volume and calcium content in animals with induced osteoporosis. In addition, the increase in new bone formation was associated with a significant restoration of bone strength back to normal levels.

Previous studies have shown that extended in vivo treatment with low-dose gallium in normal animals was associated with increased bone content of calcium and phosphorous, a decrease in bone resorption, a possible increase in new bone formation, and no deleterious effects upon bone biomechanical strength. Moreover, preliminary clinical studies in patients with bone involvement from myeloma, breast cancer, and other malignant diseases had shown biochemical evidence of decreased resorption and increased bone density. Decreased bone resorption has also been reported in patients with advanced Paget’s disease, a metabolic bone disorder. However, no studies have previously examined whether these effects could be replicated in osteoporosis, the most prevalent metabolic bone disease.

In the new studies, a model that simulates post-menopausal osteoporosis was used to induce bone loss. The active ingredient was administered for 8 weeks in an inorganic form (similar to Ganite^®) and also in an organic form (comparable to the Company’s orally available gallium-containing compounds). Micro-CT scanning showed that treatment significantly increased both trabecular and cortical bone volume by 49% and 32%, respectively. These findings were confirmed by histomorphometry. Additional analysis revealed a significant increase in bone calcium content. Since some drugs used for clinical treatment of osteoporosis (including certain bisphosphonates) are associated with a decrease in bone strength, biomechanical studies were performed in order to assess the quality of the newly formed bone. These studies showed that bone from treated animals had been restored to levels that were both fully comparable to normal controls and significantly superior to untreated osteoporotic controls.

Together, these new data confirm that – in osteoporotic bone – gallium treatment is associated with significant increases in bone mineral content, bone volume, and new bone formation that is biomechanically normal – findings that had been previously described only in bone that was normal at baseline. These data strongly suggest that gallium-containing compounds exert anti-resorptive and anabolic effects on bone metabolism, and that such compounds may be broadly useful for a wide spectrum of bone-losing disorders.