Nintedanib Is Safe and Effective in Treating Idiopathic Pulmonary Fibrosis

San Diego—Patients with idiopathic pulmonary fibrosis (IPF) who received 150 mg of nintedanib twice daily had a significant reduction in the rate of decline of forced vital capacity (FVC) compared with a placebo group, according to 2 phase 3, randomized, multinational, placebo-controlled trials. The drug also slowed disease progression and was associated with an acceptable safety profile.

Results were presented during a late-breaking abstract session at the ATS conference. They were also published online in New England Journal of Medicine [2014; DOI:10.1056/NEJMoa1402584]. Boehringer Ingelheim, the manufacturer of nintedanib, provided funding for the study.

Nintedanib, an intracellular inhibitor, is an oral medication that targets vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and fibroblast growth factor receptors. The investigational drug is being tested to treat non-small cell lung cancer, ovarian cancer, hepatic cell carcinoma, renal cell carcinoma, and colorectal cancer.

IPF, a fatal lung disease, is associated with worsening dyspnea and the progressive loss of lung function. According to the National Heart, Lung and Blood Institute, most patients with the disease live 3 to 5 years after disease onset. The most common cause of death is respiratory failure, while other causes include pulmonary hypertension, heart failure, pulmonary embolism, pneumonia, and lung cancer.

The studies had identical designs, matching dosing, inclusion criteria, and end points. They were conducted at 205 sites in 24 countries in the Americas, Europe, Asia, and Australia between May 2011 and September 2012.

Eligibility criteria included patients who were ≥40 years of age, had a diagnosis of IPF within the past 5 years, had a FVC that was ≥50% of the predicted value, and had undergone a chest high-resolution computed tomography scan within 12 months of screening.

The studies included 1066 patients who were randomized in a 3:2 ratio to receive 150 mg of nintedanib twice daily or placebo for 52 weeks. At baseline, the characteristics between the groups were similar in both studies. The mean age was approximately 66 years, the mean body mass index was approximately 28 kg/m², and 80% of patients were male.

Compared with the placebo group, patients who received nintedanib had a mean annual reduction in FVC of 125.3 mL in the first study (P<.001) and 93.7 mL in the second study (P<.001). In the first study, there was no significant difference between the groups with regard to the time to first acute exacerbation (P=.67). However, there was a significant difference in the second study (P=.005).

Gary M. Hunninghake, MD, wrote an accompanying editorial published in New England Journal of Medicine. He noted that these 2 trials plus a study examining another investigational agent (pirfenidone) may lead to choices in managing IPF, which is currently untreatable. There are also questions about whether any FDA-approved drug can alter the course of the disease, according to Dr. Hunninghake.

Dr. Hunninghake wrote that “there was no evidence of improvement in scores for respiratory symptoms” in the 2 trials and mentioned they were not powered to detect statistical differences in mortality. However, he added that “it is comforting that nintedanib resulted in a trend toward a reduced rate of death that mirrored the reduced rate of decline in lung function.”