Idiopathic pulmonary fibrosis study points to survival as key endpoint in future actimmune studies

Jan 10 2005

InterMune, Inc. today announced that CHEST, the journal of the American College of Chest Physicians, published an important analysis of variables that measure clinical outcomes in patients with idiopathic pulmonary fibrosis (IPF), a deadly and debilitating lung disease. The analysis was derived from a database of the largest completed IPF study to date, a controlled Phase III trial (GIPF-001) of Actimmune(R) (interferon gamma-1b) for treatment in 330 patients with IPF.

"The extensive database from GIPF-001 greatly enhanced our understanding of the clinical course of IPF and better informed our decisions regarding the entry criteria, endpoints, study size and duration of the on-going Phase III INSPIRE clinical trial," stated Talmadge E. King, Jr., M.D., INSPIRE study Co-Chair, Professor and Vice Chairman, Department of Medicine, University of California San Francisco, San Francisco General Hospital. "In addition to providing insights into the selection of reliable efficacy endpoints for future IPF trials, these data further support the investigation of Actimmune as a therapy to potentially prolong survival in patients with this devastating disease."

In order to determine the most appropriate study endpoint for INSPIRE, the authors undertook a retrospective analysis of the components of the composite primary efficacy endpoint in the GIPF-001 trial: death or disease progression as defined by an increase in resting alveolar-arterial oxygen pressure gradient (A-a gradient) of greater than or equal to 5 mm Hg or a decrease in forced vital capacity (FVC) of greater than or equal to 10%. In this way the authors were able to evaluate the important test characteristics, including reliability, validity and sensitivity to treatment effect, of these measures commonly used to assess treatment outcomes in patients with IPF. These factors are all critical to selecting the appropriate efficacy outcome measures in clinical trials.

These analyses showed that survival is the preferred outcome measure in future studies of Actimmune in patients with IPF. The A-a gradient criterion had uniformly poor test characteristics, and while the FVC criterion was reliable and valid, it was not sensitive to the treatment effect. Survival is a robust and immensely important clinical endpoint and is also sensitive to the treatment effect of Actimmune: nearly all patient subgroups defined by physiology had a tendency toward prolonged survival with Actimmune therapy, and this effect was strongest in patients with baseline FVC of greater than or equal to 55% (p=0.004) or diffusing capacity of greater than or equal to 30% (p=0.008).

"This analysis strongly supports the design of our ongoing Phase III INSPIRE Trial, a 600 patient placebo-controlled trial with survival as its primary endpoint," stated Dan Welch, InterMune's CEO and President. "In addition, we are encouraged by the overall consistency of the survival findings in this study and the magnitude of the treatment effect of Actimmune on survival in patients with IPF."