Genta and Emisphere Technologies file investigational new drug exemption

Genta Inc. and Emisphere Technologies, Inc. have jointly announced the submission of an Investigational New Drug Exemption (IND) to the Endocrinologic and Metabolic Drugs Division of the U.S. Food and Drug Administration (FDA) for a new drug known as G4544.

Developed out of a joint collaboration announced last year, G4544 is a new tablet formulation that enables oral absorption of the active ingredient contained in Ganite (gallium nitrate injection), a drug that is marketed by Genta and approved in the U.S. for treatment of cancer-related hypercalcemia that is resistant to hydration. The IND proposes a Phase 1 clinical trial that will examine initial safety and pharmacokinetics of G4544 in human subjects. Genta will act as Sponsor of the IND and will direct the clinical development program.

"The success of this project speaks to the expertise of Emisphere in developing and deploying our patented technology to address poorly absorbed compounds for broader patient use," said Michael Novinski, Chairman and Chief Executive Officer of Emisphere Technologies. "We are excited by the prospect of helping make treatments easier for a broad array of patients."

"Genta has pursued this project for a number of years, and we are very pleased with the results of our collaboration with Emisphere," said Dr. Raymond P. Warrell, Jr., Chairman and Chief Executive Officer of Genta. "With this success, G4544 significantly extends our intellectual property associated with the gallium products franchise. Our initial focus will be to establish clinical bioequivalence with our parenteral product. However, the active ingredient in G4544 has already demonstrated proof-of-concept activity in patients with multiple indications, including non-Hodgkin's lymphoma, bone metastases, Paget's disease, and osteoporosis. Going forward, Genta plans to manage the clinical development programs in oncology, and we intend to seek a partner for programs in metabolic bone disease."

Gallium-Containing Compounds

Gallium-containing compounds were originally developed by the U.S. National Cancer Institute. In investigational studies, high doses of gallium nitrate demonstrated consistent antitumor activity in patients with non- Hodgkin's lymphoma. However, experimental work by Genta personnel and others established that lower doses of gallium directly inhibited calcium release from bone, principally by decreasing bone resorption and possibly by also stimulating bone formation.

Many diseases are associated with accelerated bone loss, including osteoporosis, cancer, and Paget's disease. In some diseases, the rate of loss is slow and subtle, while in others the rate is rapid and acute. In osteoporosis, the most prevalent bone-losing condition, the process of bone loss extends over many years before the disease becomes evident. Conversely, in cancer-related hypercalcemia, bone loss is so rapid that it overwhelms the kidney's ability to eliminate calcium from the blood, and this condition can quickly become lethal.

In patients with cancer-related hypercalcemia who were resistant to hydration, randomized double-blind trials have been conducted with Ganite compared with calcitonin and with two bisphosphonates (etidronate [Didronel(R); Proctor and Gamble] and pamidronate [Aredia(R); Novartis, Inc.]). However, the approved dose-schedule for Ganite calls for administration as a continuous intravenous infusion for up to 5 days, which has generally limited its use to patients with severe bisphosphonate- refractory disease.

Oral Gallium (G4544)

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 intravenous pumps or hospitalization. The initial focus of clinical studies with G4544 will be to establish its bioequivalence with the intravenous product, potentially enabling rapid regulatory approval of the oral formulation.