Inspire Pharmaceuticals, Inc. announced top-line results from the 352-patient, double-blind, 24-week placebo-controlled portion of its phase III trial (TIGER-1) with denufosol tetrasodium inhalation solution for the treatment of cystic fibrosis (CF).

The trial demonstrated statistical significance for its primary efficacy endpoint, which was the change in FEV1 (Forced Expiratory Volume in One Second) from baseline at the trial endpoint (at 24 weeks or last observation carried forward). Patients treated with denufosol had a statistically significant improvement in FEV1 compared to placebo. On average, patients on denufosol improved relative to baseline whereas patients on placebo remained essentially unchanged. The treatment effect of denufosol increased over the 24-week placebo-controlled period, and available preliminary data from approximately 210 patients who have completed the ongoing open-label safety extension (including the placebo patients switched to denufosol) suggest that FEV1 continued to improve during the extension period from weeks 24 to 48.

Secondary endpoints were also evaluated in the trial. There was a trend in differences in FEF, a measure of small airway function, favouring denufosol over placebo. There were no statistically significant differences between denufosol and placebo relative to pulmonary exacerbations. Data analysis is ongoing for various other pre-specified secondary endpoints and sub-groups.

For the 352 subjects randomized, the treatment groups were balanced with respect to key demographic and background characteristics: the mean age was approximately 14.6 years old, the mean lung function at baseline was 92 per cent of the predicted normal value of FEV1, and the use of concomitant medications included inhaled antibiotics (37%), dornase alfa (Pulmozyme) (77%) and oral macrolide antibiotics (40%). Approximately, one-half of patients were receiving three or more pulmonary medications for the treatment of their disease during the course of this trial. This trial demonstrated that the effects of denufosol on FEV1 were beneficial in this population of patients taking multiple commonly-prescribed CF pulmonary medications.

Denufosol was well-tolerated and had a favourable safety profile in the trial. Patient retention rates were high and similar between treatment groups with approximately 90 per cent of patients completing the 24-week placebo-controlled portion. The incidence of adverse events in the denufosol group was comparable to placebo. As in previous trials, the most common adverse event was cough, which was similar in both groups. There were no apparent treatment effects with respect to height, weight or body mass index. The clinical laboratory profiles were similar between the groups. Seven patients withdrew due to adverse events (five denufosol and two placebo recipients).

Following the 24-week placebo-controlled period, approximately 315 patients continued into the open-label safety extension portion of the trial and approximately 213 of those patients have now completed the full trial for a total of 48 weeks. The patient discontinuation rate in the open-label safety extension is currently less than 4 per cent.

Frank J Accurso, MD, Professor of Paediatrics and Cystic Fibrosis Center director, University of Colorado and The Children's Hospital Denver, and lead principal investigator of TIGER-1, stated "The results from this trial are exciting because they demonstrate that denufosol's novel mechanism of action, activation of an alternative chloride channel that is treating the underlying defect, had a clinically-meaningful impact on lung function that progressively increased over time. The improvement in FEV1 was achieved on top of aggressive use of multiple concomitant medications, such as inhaled antibiotics, dornase alfa and oral macrolide antibiotics. The benefit in lung function observed in these relatively young patients, with a mean age of around 14 years, was encouraging. In particular, adolescence is an especially vulnerable time for these patients, where lung function generally declines. In this trial, denufosol had a favourable safety profile and provided benefit to CF patients".

Robert J Beall, Ph.D., president and CEO, Cystic Fibrosis Foundation, commented, "The data from this phase III trial with denufosol are encouraging for the cystic fibrosis community because it brings us one step closer to a novel treatment that addresses the basic cystic fibrosis defect.

"We are pleased that denufosol met the primary efficacy endpoint in TIGER-1 and we will continue to work toward bringing this new treatment to the cystic fibrosis community," stated Christy L. Shaffer, Ph.D., president and CEO of Inspire. "We would like to thank the Cystic Fibrosis Foundation, the Therapeutics Development Network and all of the dedicated patients, investigators, and study coordinators who participated in TIGER-1. We also want to thank the patients' families for their support and interest in denufosol. We plan to use the valuable information generated in this trial to further optimize TIGER-2 which began enrolling patients a few months ago".