New IPF Therapies Highlighted at European Respiratory Society Annual Congress in Stockholm
Actimmune Phase III and Pirfenidone Phase II Data Presented
Wednesday September 18, 8:00 am ET
BRISBANE, Calif. and STOCKHOLM, Sweden, Sept. 18 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN - News) announced today that data from its recently completed Phase III clinical trial of Actimmune® (Interferon gamma-1b) injection for the treatment of idiopathic pulmonary fibrosis (IPF), a debilitating and usually fatal lung disease, were presented during two separate scientific sessions of the European Respiratory Society (ERS) Annual Congress 2002 in Stockholm. Data were also presented from a Phase II clinical study with pirfenidone, an oral agent also being developed by InterMune for IPF.
Paul Noble, M.D., Associate Professor of Medicine, Yale University School of Medicine, presented Actimmune IPF Phase III data at an ERS symposium entitled Management Strategies and Treatment Options for Patients with IPF. Talmadge E. King, Jr., M.D., Professor and Vice Chairman, Department of Medicine, University of California San Francisco, presented the Actimmune Phase III and pirfenidone Phase II data at a session entitled Treatment Advances and Failures in Pulmonary Fibrosis.
Actimmune IPF Phase III Results
The researchers reported that a total of 330 patients were randomized into InterMune's double-blind, placebo-controlled Phase III trial, which was conducted at 58 centers in North America, Europe and South Africa. Patients received either placebo or 200 micrograms of Actimmune injected subcutaneously three times per week. Median observation duration was 60 weeks at the pre-specified time of data cut-off for the analysis. The study included a well-defined cohort of IPF patients, and treatment groups were well balanced by baseline characteristics. There was also a very high level of patient retention and compliance with study treatment in the Actimmune and placebo groups (93.6% vs. 92.1%, respectively).
The primary endpoint was progression-free survival defined as the first occurrence of one of the following: (i) a decrease in forced vital capacity (FVC) of greater than or equal to 10 percent, (ii) an increase in A-a gradient greater than or equal to 5 mmHg, or (iii) death. In the Actimmune-treated group, 75/162 patients (46.3%) experienced death or disease progression compared to 87/168 patients in the placebo group (51.8%). This represents an 11% relative reduction in the rate of progression-free survival in patients receiving Actimmune, a result that did not achieve statistical significance (p = 0.53).
Secondary endpoints included dyspnea, individual measures of pulmonary function, oxygen use and survival. Exploratory analyses suggested trends for less dyspnea after 48 weeks of treatment and less oxygen use in the Actimmune-treated group versus placebo. The researchers also reported a trend in improved survival in favor of Actimmune. In the overall intent-to-treat patient population, there were 16/162 deaths in the Actimmune treated group (9.9%) compared to 28/168 deaths in the placebo group (16.7%), representing a 40% decrease in mortality in favor of Actimmune (p = 0.084). Further evidence on some secondary endpoints, including survival, will be available when data collection is complete on the blinded phase of study extension.
A number of exploratory analyses were undertaken to better understand this trend in survival. An analysis of survival in protocol-eligible patients -- defined as all patients that met the eligibility criteria for the lower limit of FVC, PaO(2), and DL(co) at baseline -- revealed 12/149 death@®æ the Actimmune-treated group (8.1%) and 24/153 deaths in the placebo group (15.7%). This represents a 49% decrease in mortality in favor of Actimmune (p = 0.055).
An exploratory analysis of mortality based on the median baseline FVC in the study was also reported. In those patients with FVC greater than 60% at study entry, there were 3/90 deaths in the Actimmune-treated group (3.3%) versus 12/92 deaths in the placebo group (13%). This represents a 74% decrease in mortality in patients with less impairment in lung function. In contrast, in patients with FVC less than or equal to 60% at study entry, there were 13/72 deaths in the Actimmune treated group (18%) versus 16/76 in the placebo group (21%), suggesting little mortality benefit in patients with greater impairment.
These exploratory analyses suggest that patients with mild to moderate impairment in lung function at study entry may be more likely to benefit from Actimmune. The researchers also noted that most deaths were respiratory related and occurred more acutely in the placebo group. Actimmune was generally well tolerated with few discontinuations due to adverse events, though there were a greater number of non-fatal pneumonias in the Actimmune treated group versus placebo.
Pirfenidone Phase II Results
Dr. King also presented the results of a Phase II study with pirfenidone in IPF. This double-blind placebo-controlled trial randomized 111 patients to either pirfenidone or placebo for 48 weeks. The primary endpoint was arterial oxygen saturation during a standard six-minute walk test. Secondary endpoints included measures of pulmonary function and dyspnea.
The trial's Data Safety and Monitoring Board stopped the study after six months due to an imbalance in life threatening acute exacerbations in favor of pirfenidone. At the time the study was ended, there was a trend for efficacy in the primary endpoint in the overall population of pirfenidone treated patients and a significant effect on the primary endpoint in a pre-specified group of those patients who could complete the standard six-minute walk test at baseline. There were also trends for efficacy in favor of pirfenidone in the secondary endpoints. Pirfenidone was generally well tolerated with the most frequent side effect reported being moderate photosensitivity. Gastrointestinal upset was also noted in some patients. The study's sponsor, Shionogi & Co., Ltd., is in the process of preparing an NDA in Japan. InterMune plans to conduct additional clinical trials to confirm these findings.
"We are pleased that two of our compounds for IPF were so prominently featured at this important international medical conference," said W. Scott Harkonen, M.D., Chief Executive Officer and Chairman of InterMune. "We look forward to reporting further analyses and results at the CHEST meeting in November and continuing clinical trials with these promising agents throughout the world to substantiate these potential benefits."
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