InterMune Announces Favorable New Clinical Results of Actimmune(R) In Idiopathic Pulmonary Fibrosis
Monday May 19, 9:02 am ET
Results Continue to Support Potential Survival Benefit for IPF Patients
SEATTLE and BRISBANE, Calif., May 19 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN - News) announced today that favorable new follow-up data from its Phase III clinical trial of Actimmune® (interferon gamma-1b) in idiopathic pulmonary fibrosis (IPF), and clinical study results from an interim analysis of an independent European study of interferon gamma-1b in IPF were presented at the 99th International Conference of the American Thoracic Society (ATS) in Seattle.
ADVERTISEMENT
Investigators reviewed a final primary data analysis from InterMune's Phase III randomized, placebo controlled, double-blind trial evaluating interferon gamma-1b therapy in patients with IPF, as well as exploratory analyses from a follow-up observation period and new follow-up survival data (from time of randomization through May 5, 2003). Separately, European investigators presented new results from an interim analysis of an independent randomized controlled clinical trial in which a statistically significant survival benefit (p = 0.01) was observed in IPF patients treated with interferon gamma-1b.
"A survival benefit has now been observed in three out of three randomized, controlled clinical trials with interferon gamma-1b. Interferon gamma-1b has also been shown to be very well tolerated in over a dozen years of clinical use in many indications," said James E. Pennington, M.D., InterMune's Executive Vice President of Medical and Scientific Affairs. "We are also extremely excited by the May 5th follow-up data, which is consistent with previously observed survival observations. We look forward to meeting with the FDA this year to discuss all the existing data and refine our plans for an additional survival trial."
Phase III Results Review
A randomized, double-blind, placebo-controlled Phase III study of 200 micrograms of interferon gamma-1b administered subcutaneously three times per week was conducted in 330 IPF patients at 58 centers in the United States, Europe and South Africa. Median duration of follow-up was 59 weeks.
The primary efficacy endpoint was time to either death or disease progression (as defined by either greater than or equal to 10% decrease in % predicted forced vital capacity (FVC) or greater than or equal to 5mm Hg increase in A-a gradient). Additional efficacy endpoints included patient symptoms, measures of disease progression, duration of hospitalization and survival.
According to a review of the final primary analysis (Sept. 13, 2000 through June 26, 2002), there was no significant treatment effect on the primary endpoint, conventional measures of physiologic function or quality-of-life scales. However, a pre-specified analysis of survival, a secondary endpoint in the trial, suggested that interferon gamma-1b confers a survival benefit to IPF patients in the intent-to-treat population (41% relative reduction in the risk of death: p = 0.08). This survival benefit was more pronounced in the pre-specified cohort of treatment adherent patients (66% relative reduction in risk of death: p = 0.02), defined as patients receiving greater than 80% of scheduled doses and in patients who had less severely impaired lung function (FVC greater than or equal to 55%) at baseline (71% relative reduction in risk of death: p = 0.004). In addition, an exploratory analysis suggested a trend toward less dyspnea (i.e., difficulty breathing) after 48 weeks, according to the Transition Dyspnea Index (TDI) score.
Exploratory Analyses from Follow-up Observation Period
In exploratory analyses from the follow-up observation period (from time of randomization through November 30, 2002), again no significant treatment effects on conventional markers of physiologic function were observed. However, a possible treatment benefit of interferon gamma-1b on dyspnea continued to be observed, according to the TDI score.
Exploratory analyses also suggested a survival benefit associated with interferon gamma-1b treatment with a trend toward improved overall survival in the intent-to-treat analysis (25% relative risk reduction in the risk of death; p = 0.17). Significantly improved survival was observed in two large, independent subgroups of interferon gamma-1b-treated IPF patients, those with mild-to-moderate disease at baseline and a pre-specified, treatment-adherent cohort. Interferon gamma-1b-treated IPF patients who had less severely impaired lung function (FVC greater than or equal to 55% and DL(co) greater than or equal to 35%) at baseline exhibited a 74% relative reduction in risk of death (p = 0.02). A 47% relative reduction in risk of death (p = 0.04) was observed in patients adherent to interferon gamma-1b treatment.
Moreover, shorter duration of hospitalizations for respiratory admissions was seen in interferon gamma-1b-treated patients, particularly those with less severe baseline impairment of lung function.
Interferon gamma-1b generally was well tolerated. The proportion of patients with reported pneumonia was slightly higher in the interferon gamma-1b group (14.8%) than in the placebo group (10.1%). However, there was no imbalance of patients with recurrent, severe/life-threatening, or fatal pneumonias. The adverse events were consistent with the known safety profile of interferon gamma-1b.
Long-Term Survival Data
Long-term survival data (from time of initial randomization through May 5, 2003) was also presented. Blinded study treatment ended in all patients by Nov. 30, 2002, and over 80% of patients who completed the study opted to receive interferon gamma-1b in an open-label extension study. Assessment of patient vital status ten months after study completion on June 26th continues to suggest enhanced survival in patients initially randomized to interferon gamma-1b treatment. Occurrence of death in the intent-to-treat population was 17.9% (29/162) in interferon gamma-1b-treated patients and 25.6% (43/168) in placebo-treated patients, respectively (30% relative reduction in risk of death; p = 0.07). Interferon gamma-1b-treated IPF patients who had less severely impaired lung function (FVC greater than or equal to 55% and DL(co) greater than or equal to 35%) at baseline exhibited a 51% relative reduction in risk of death (p = 0.009).
"These data suggest that interferon gamma-1b may confer a survival benefit in patients with IPF, particularly in those adhering to the treatment regimen and in those with less severely impaired lung function," said Paul Noble, M.D., Professor of Medicine, Yale University School of Medicine, and an investigator and member of InterMune's protocol steering committee for the Phase III trial. "This is the first large, placebo controlled trial to suggest a potential survival benefit in IPF. We are excited about this observation and feel it is important to conduct a confirmatory survival trial."
Independent European Trial Results Review
A prospective, multi-center, randomized controlled trial is currently being conducted by the Hellenic Interstitial Lung Disease Group in Greece. At ATS, the investigators reported interim data on 42 patients randomized to receive interferon gamma-1b plus prednisone or oral colchicine plus prednisone.
An interim analysis of survival showed 2/27 (7.4%) patients in the interferon gamma-1b-treated group and 6/15 (40%) patients in the colchicine-treated group had died, respectively, representing an 81% relative reduction in the risk of death in favor of the interferon gamma-1b group (p = 0.01). Consistent with InterMune's phase III trial, there appeared to be minimal treatment effect on conventional physiologic measures of disease progression.
"Our preliminary findings show improved survival with interferon gamma-1b treatment versus colchicine treatment in IPF, and we are pleased that these results are consistent with those of other controlled trials with respect to the prolongation of survival time observed in IPF patients treated with interferon gamma-1b," said Demosthenes Bouros, M.D., Professor of Medicine, Medical School University of Thrace and a principal investigator in the trial. "We believe that interferon gamma-1b is a promising therapeutic that offers IPF patients hope for improved survival against this uniformly fatal disease."
About Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia. Once symptoms appear, there is a relentless deterioration of pulmonary function and median survival of 2.8 years after diagnosis. There are currently no drugs approved by the FDA for the treatment of IPF. Approximately 75,000 patients suffer from this disease in the United States.
About Actimmune® (interferon gamma-1b)
Interferon gamma is a naturally occurring protein that stimulates the immune system. InterMune markets Actimmune® for the treatment of two life-threatening congenital diseases: chronic granulomatous disease and severe, malignant osteopetrosis. The most commons side effects are flu-like symptoms, including fever, headache and chills. InterMune is also conducting a Phase III study of interferon gamma-1b in ovarian cancer and a Phase II study of interferon gamma-1b for the treatment of severe liver fibrosis, or cirrhosis, caused by hepatitis C virus (HCV). Physicians and patients can obtain additional prescribing information regarding Actimmune®, including the product's safety profile, by visiting actimmune.com .
About InterMune
InterMune is a commercially driven biopharmaceutical company focused on the marketing, development and applied research of life-saving therapies for pulmonary, infectious and hepatic diseases. For additional information about InterMune, please visit intermune.com .
<snip> |
