BERKELEY HEIGHTS, N.J., Sept. 17 Genta Inc.(Nasdaq: GNTA) announced that the Food and Drug Administration (FDA) hasallowed the Investigational New Drug (IND) exemption that was submitted by theCompany for its new drug known as G4544. In addition, Genta also announcedthat the first cohort of 6 normal volunteers has been treated with singledoses of G4544 without experiencing significant side effects.
G4544 is a new tablet formulation that enables oral absorption of theactive ingredient contained in Ganite(R) (gallium nitrate injection), a drugthat is marketed by Genta and approved in the U.S. for treatment of cancer-related hypercalcemia that is resistant to hydration. The initial clinicalstudy is a dose-ranging, single-dose evaluation of G4544 that will examinesafety and pharmacokinetics of G4544 in human subjects. Genta is the INDSponsor and is directing the clinical development program.
"The active ingredient in G4544 has shown a consistently high level ofclinical activity across a range of skeletal diseases," said Dr. Raymond P.Warrell, Jr., Chairman and Chief Executive Officer of Genta. "Heretofore, aninconvenient dosing schedule has precluded broader use of the IV drug, whichmay now be resolved with the new oral formulation. We believe that emergingsafety issues, such as osteonecrosis, that have been associated with the majorcompetitive drug class of bisphosphonates, can be avoided with G4544. From aregulatory standpoint, we seek to establish bioequivalence to our IV drug,while conducting the additional preclinical and clinical studies to developrepeat-dose programs that may lead to rapid approval in hypercalcemia. Wealso foresee the potential for subsequent approvals in other diseases, such asnon-Hodgkin's lymphoma, bone metastases, Paget's disease, and osteoporosis.Genta plans to manage the G4544 development program in oncology, and we intendto seek a partner for clinical programs in metabolic bone disease."
G4544 is one of a class of gallium-containing compounds that wereoriginally developed by the U.S. National Cancer Institute. Ininvestigational studies, high doses of gallium nitrate demonstrated consistentantitumor activity in patients with non-Hodgkin's lymphoma. However,experimental work by Genta personnel and others established that lower dosesof gallium directly inhibited calcium release from bone, principally bydecreasing bone resorption and possibly by also stimulating bone formation.
Many diseases are associated with accelerated bone loss, includingosteoporosis, cancer, and Paget's disease. In some diseases, the rate of lossis slow and subtle, while in others the rate is rapid and acutely life-threatening. In osteoporosis, the most prevalent bone-losing condition, theprocess of bone loss extends over many years before the disease becomesevident. Conversely, in cancer-related hypercalcemia, bone loss is so rapidthat it overwhelms the kidney's ability to eliminate calcium from the blood,and this condition can quickly become lethal. In patients with cancer-relatedhypercalcemia who were resistant to hydration, randomized double-blind trialshave been conducted with Ganite compared with calcitonin and with twobisphosphonates (etidronate [Didronel(R); Proctor and Gamble] and pamidronate[Aredia(R); Novartis, Inc.]).
G4544 was developed to enable extended administration of the activeingredient in Ganite, which may greatly improve patient convenience and avoidthe current need for intravenous pumps or hospitalization. The initial focusof clinical studies with G4544 will be to establish its bioequivalence withthe intravenous product, potentially enabling rapid regulatory approval of theoral formulation. Genta holds or has exclusively licensed the intellectualproperty related to G4544.
Genta Incorporated is a biopharmace