BUSINESS WIRE; Thursday July 2, 8:29 am EST
Lodenosine is a purine-based reverse transcriptase inhibitor (RTI) that has shown activity against clinical isolates that are resistant to other commercially available agents.
The drug has demonstrated anti-HIV activity even in patients who had failed other anti-retroviral therapies such as AZT (zidovudine), 3TC (lamivudine) and d4T (stavudine). Lodenosine was identified as an anti-HIV agent at the NCI and is being developed by U.S. Bioscience (West Conshohocken, PA, USA) in collaboration with the NCI (Bethesda, MD, USA).
Investigators from the NCI presented two abstracts on the Phase I trial of lodenosine therapy. The abstract titled, "A Phase I Dose Escalation Study of FddA (Lodenosine) in Patients with Symptomatic HIV Infection," presented by Richard Little, M.D., reports the results of 25 patients with symptomatic HIV infection and CD4 counts less than 500 cells/mm3 who were treated with 12 weeks of lodenosine monotherapy. Nineteen of the 25 patients had received more than six months of prior anti-retroviral therapy.
The 25 patients were assigned to five dose levels of lodenosine ranging from 0.2 to 3.2 mg/kg twice daily. Eight patients tested to date on the highest two doses (1.6 and 3.2 mg/kg twice daily) had a median decrease in viral load of -0.42 log10 copies/ml at week six.
A downward trend in viral load was also seen in patients at the 0.4 and 0.8 mg/kg doses. The decrease in viral load at the highest lodenosine doses correlates with an upward trend in CD4 counts. In this study, lodenosine therapy over 12 weeks was well tolerated, even in patients with substantial prior anti-retroviral therapy.
The second abstract, "The Pharmacokinetics and Oral Bioavailability of Lodenosine (FddA), a Uniquely Stable Anti-HIV Drug, in Adults with Symptomatic HIV Infection," presented by James A. Kelley, Ph.D., reported on the oral bioavailability of lodenosine.
At the 1.6 mg/kg and 3.2 mg/kg twice daily doses, lodenosine capsules were 75% bioavailable in a fasting state and 65% bioavailable when administered with food.
"Lodenosine's anti-HIV activity in these patients, most of whom have had extensive prior therapy, is consistent with its unique resistance profile," noted Robert Yarchoan, M.D., NCI principal investigator.
"Lodenosine has been shown to have activity against clinical isolates, including those with mutations at codon 151, which usually results in multi-drug resistance. Sequencing three pairs of HIV-1 from patients who received lodenosine 1.6 mg/kg twice a day for three months in the NCI's trial showed no new mutations," said Dr. Yarchoan.
"Based on the clinical profile seen thus far and its excellent oral bioavailability, we have initiated a study of lodenosine as part of triple combination therapy."
U.S. Bioscience is collaborating with the NCI on the development of lodenosine, under a Cooperative Research and Development Agreement (CRADA). The company plans to complement the NIH/NCI studies with NDA-directed clinical trials. "We are moving forward with development of lodenosine," said C. Boyd Clarke, president and CEO, U.S. Bioscience. "The emerging clinical profile is encouraging and U.S. Bioscience welcomes the opportunity to participate in this important therapeutic area."
U.S. Bioscience, Inc. (http://www.usbio.com), based in West Conshohocken, Pa., is a pharmaceutical company specializing in the development and commercialization of products for patients with cancer and AIDS.
This release contains forward-looking statements which reflect management's current views of future events and operations.
These forward-looking statements involve risks and uncertainties, including clinical trials, regulatory approvals, patent matters, market conditions, manufacturing and supply conditions, and other factors that could cause actual results to differ materially from those anticipated in any forward-looking statement.
Additional information on factors that could cause such changes is contained in the company's Securities and Exchange Commission filings, copies of which are available from the company without charge.
Contact: U.S. Bioscience Inc., West Conshohocken, Pa. Robert I. Kriebel, 800/898-4404
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