Targeted Genetics Corporation has announced encouraging results of its Phase II clinical trial in patients with cystic fibrosis. The product candidate, tgAAVCF, met its primary endpoint demonstrating safety and tolerability in this first ever repeat dosing study. Positive trends in pulmonary function, IL-8 levels and gene transfer was also observed.

tgAAVCF, Targeted Genetics'' lead gene therapy product candidate for the treatment of cystic fibrosis, was tested in a randomized, double-blind, placebo-controlled clinical trial that included 37 patients with mild cystic fibrosis. Preliminary aggregate data analysis suggests that the aerosolized product, administered via nebulizer to the lung, was safe and well tolerated by patients. No clinically significant differences in adverse events or laboratory parameters between placebo and tgAAVCF-treated patients were observed. Patients were also monitored for overall lung function (FEV1 - a standard measure of lung function) at days 30, 60 and 90 and showed statistically significant improvement at day 30 of treatment (p=.04). Levels of IL-8, a cytokine associated with inflammation, were lower in tgAAVCF patients after 14 days compared to placebo. Excellent gene transfer was also observed in all patients tested, as measured by DNA PCR on cells removed by a bronchoscopy procedure. Gene expression was not demonstrated and AAV neutralizing antibody response occurred systemically and locally.

"No other gene-based therapies have been able to impact cystic fibrosis in this way, and I am very encouraged by the safety and tolerability of repeated delivery of tgAAVCF in CF patients. I am also encouraged by short-term improvements in lung function and reduced inflammatory cytokine IL-8 in these patients," said Richard B. Moss, lead clinical investigator, Pediatric Pulmonary Medicine, Stanford University Medical Center. "This trial has yielded interesting data, and is another step toward better understanding the role of AAV-based therapies in correcting the underlying genetic defect in the treatment of this inherited disease. I look forward to completing the analysis of the full data set once we have completed follow-up on all patients in the study. I believe these data will help us to understand the potential of tgAAVCF in the treatment of cystic fibrosis."

This phase II clinical trial involved 37 CF patients with mild lung disease, 17 of whom received placebo. The mean age in this study was 24 years. Following approvals from an independent data safety monitoring board last year, patients as young as 12 years of age were included in the clinical trial. Patients were randomized to receive three doses at 30-day intervals of tgAAVCF, 1013 DNAse resistant particles (DRP) per dose, or placebo. Patients were followed for 90 days after receiving their last dose. Aggregate data have been analyzed for the purposes of this presentation. When all patients have been monitored for a total of 150 days, full analysis of data will be completed as well as analysis of individual patient data. The primary endpoint of this study was the safety and tolerability of repeat dosing with tgAAVCF. Activity measures included lung function, inflammation and microbiology. In a subset of patients, gene transfer was evaluated as well. The trial was conducted in collaboration with the Cystic Fibrosis Foundation''s Therapeutics Development Network.

"The Cystic Fibrosis Foundation''s Therapeutics Development Network (TDN) is proud to have partnered with Targeted Genetics to conduct this Phase II trial," said Bonnie Ramsey M.D., Director of the Cystic Fibrosis Foundation TDN. "I am encouraged by the results of this study, and believe gene therapy has potential to bring about new possibilities for treatment of CF. The TDN appreciates the effort put forth by Targeted Genetics to conduct gene therapy research for the benefit of CF patients and we look forward to working with Targeted Genetics on future studies."