Initial results of gallium-containing compound to treat serious infection presented at AACR 2010

Apr 21 2010

Genta Incorporated (OTCBB: GETA) today announced the presentation of initial results from the first human use of a gallium-containing compound to treat serious infection. In a patient with cystic fibrosis and a highly resistant lung infection, who has been treated over a 2-year period, high concentrations of gallium were achieved in sputum. Moreover, sputum concentrations were higher than simultaneous concentrations in blood and continued to rise even after treatment had been stopped. Measured concentrations in sputum equaled or exceeded concentrations that have been reported lethal to bacteria in laboratory tests. The data were presented at the annual meeting of the American Association of Cancer Research in Washington, D.C.

“These data show that gallium is preferentially concentrated in sputum of infected lungs”

Gallium is known to interfere with certain iron-dependent metabolic processes, which can be lethal to single-cell organisms such as bacteria, mycobacteria (e.g., tuberculosis), protozoa (e.g., malaria), and fungi. Infection is the most common cause of death in patients with cystic fibrosis, which are frequently caused by bacteria known as Pseudomonas aeruginosa that have become highly resistant after years of antibiotic therapy. Recent laboratory data have suggested that gallium may kill these bacteria and also augment the activity of standard antibiotics.

In a preliminary clinical test, a patient with cystic fibrosis and extensive lung infection due to highly resistant Pseudomonas was treated with intermittent intravenous (IV) infusions of gallium nitrate (administered as Ganite^® [gallium nitrate injection]) over a 2-year period. Blood and sputum concentrations were measured during and after two of these infusions.

Sputum gallium concentrations from infected lungs were consistently higher than levels simultaneously obtained in plasma. In the 2 cycles of treatment with pharmacologic monitoring, these concentrations substantially exceeded levels that laboratory tests had previously shown were lethal to resistant Pseudomonas. Moreover, gallium concentrations in sputum continued to rise even after IV therapy was discontinued. Extended treatment with IV gallium nitrate was well-tolerated despite the presence of extensive lung disease and substantial compromise of pulmonary function. Previously deteriorating clinical status due to pulmonary failure was stable over the 2-year period.

"These data show that gallium is preferentially concentrated in sputum of infected lungs," said Dr. Raymond P. Warrell, Jr., Genta's Chief Executive Officer. "High levels were achieved and sustained during short courses of treatment -- an especially promising result that should obviate any need to consider direct inhalation. A new clinical trial to formally evaluate IV gallium nitrate in patients with cystic fibrosis will begin next month. These preliminary data also suggest that our oral gallium-containing compound may be useful for this purpose as chronic therapy."

The potential use(s) described in this release are investigational and have not been approved. Genta is exclusively marketing an IV form of gallium nitrate (Ganite^® [gallium nitrate injection]), which is indicated for treatment of symptomatic patients with cancer-related hypercalcemia that is resistant to hydration. The Company has also developed proprietary oral formulations of the active ingredient in Ganite^® that are being evaluated as potential treatments for diseases associated with accelerated bone loss.

The new clinical trial discussed in this release is expected to begin in May 2010 and will enroll patients with cystic fibrosis who will be treated at the University of Washington, Seattle, WA, and the University of Iowa, Iowa City, IA. If initial results are promising, additional trials may be conducted at other medical centers in a larger number of patients. For this trial, Genta has provided cross-reference to its Investigational New Drug (IND) exemption for Ganite^®, and the Company will supply the drug at no cost to patients in the trial. The study is supported by grants from the Orphan Products Division of the Food and Drug Administration (FDA) and the Cystic Fibrosis Foundation.