Genta Inc (BERKELEY HEIGHTS, New Jersey), a biopharmaceutical company with a diversified product portfolio, announced the release of final results from the phase I clinical trial of G4544, a proprietary small molecule to treat diseases associated with accelerated bone loss including osteoporosis, Paget’s disease, hypercalcemia, and bone metastasis (myeloma and breast cancer). Results showed that the drug was well-tolerated and that blood levels were achieved in a range known to be clinically bioactive.  

The trial tested escalating single doses of G4544 30 mg to 150 mg in 30 normal volunteers. The study endpoints were to determine safety and to assess pharmacokinetics and oral bioavailability. No adverse effects attributable to G4544 were observed.

G4544 is a new tablet formulation using delivery technology developed by Emisphere Technologies, Inc that enables oral absorption of the active ingredient contained in Ganite^® (gallium nitrate). Ganite is marketed by Genta and is approved in the US for treatment of symptomatic patients with cancer-related hypercalcemia that is resistant to hydration.

Gallium-containing compounds are potent inhibitors of bone resorption. Gallium reduces bone loss by inhibiting calcium resorption from bone. Preclinical evidence of the drug suggests that the mechanism of action is multifactorial and different from other current therapies such as estrogen or selective estrogen receptor modulators, calcitonin, or bisphosphonates (eg, Zometa^® or Fosamax^®) used to treat bone loss. Gallium preferentially accumulates in metabolically active regions of bone, inhibits osteoclast-mediated bone resorption, and favorably alters bone mineral composition and properties.

Low doses of gallium nitrate administered by intravenous (IV) or subcutaneous injections have shown clinical activity in a range of skeletal diseases. G4544 was developed to enable extended administration of the active ingredient in Ganite, which may greatly improve patient convenience and avoid the current need for extended IV infusion or hospitalization.

The initial focus of clinical studies with G4544 will be to evaluate bioequivalence with the IV drug, potentially enabling rapid regulatory approval. Genta will construct plans for future clinical development in oncology and will seek a partner for development in osteoporosis and Paget’s disease. Genta holds or has exclusively licensed the intellectual property related to G4544.