A new article that reviews available treatment options for idiopathic pulmonary fibrosis (IPF) took a critical but positive look at available research information for OFEV (nintedanib). The article focuses on the clinical evidence supporting nintedanib as an IPF treatment and on the drug’s pharmacological characteristics.
The article, titled “Idiopathic pulmonary fibrosis: current treatment options and critical appraisal of nintedanib“ by Francesco Bonella and colleagues from the University of Duisburg-Essen, Germany, in collaboration with Boehringer Ingelheim, was published in the journal Drug Design, Development, and Therapy.
The development of novel IPF drugs has followed the knowledge curve of disease pathogenesis. As a result of increased insight into disease mechanisms, two novel IPF drugs have recently been introduced to the market, revolutionizing IPF treatment. One of them is OFEV (nintedanib) by Boehringer Ingelheim.
The goal of current IPF treatment is to stop disease progression, reduce symptoms and prevent acute exacerbations, with the ultimate long-term goal of prolonging survival. The review states that all care — whether preventive, rehabilitative, or based on symptom treatment — needs to be started early to minimize the decline in quality of life that follows diagnosis. Shortness of breath, a typical symptom in IPF, prevents many patients from being active. Inactivity, in turn, causes loss of muscle mass and chronic fatigue, inducing a downward health spiral.
The feasibility of oxygen treatment has not been subject to clinical trials, but studies show that long-term oxygen therapy leads to better social and physical performance, contributing to a better quality of life. Lung transplant is also a IPF recommended treatment option, reducing mortality by 75 percent.
Pharmaceutical treatment has, as stated, seen a remarkable transformation. Before the U.S. Food and Drug Administration approved OFEV (nintedanib) and Esbriet (pirfenidone) in 2014, a clinical trial showed that N-acetylcysteine, the previous common treatment, had no effect on forced vital capacity (FVC), a measure of lung function, in IPF patients.
Both OFEV and Esbriet are antifibrotic drugs shown to reduce the decline in FVC by 50 percent in one year. However, no studies to date have compared OFEV and Esbriet, and since the clinical trials leading to the approval of the two drugs included slightly different groups of patients, a direct comparison between the trials is not possible.
There also have not been any large studies investigating whether the combination of OFEV and Esbriet could offer a synergistic effect, with a maintained safety profile. A Japanese Phase 2 clinical trial involving 50 patients showed that when the drugs were given in combination, the plasma levels of OFEV was reduced compared to OFEV monotherapy. The study was, however, too small to draw any conclusions about safety and efficacy.
OFEV is a tyrosine kinase inhibitor, and the detailed molecular mechanisms of OFEV treatment were studied in both in vitro and in experimental animal models. OFEV can inhibit the proliferation and migration of human lung fibroblasts in culture. The drug also inhibits the transformation of fibroblasts to myofibroblasts — a cell type contributing to fibrosis development — by inhibiting TGF-β. Some data also showed that OFEV can reduce the secretion of extracellular matrix components. Studies on animal models of lung fibrosis showed that OFEV treatment reduced both inflammation and fibrosis. Indications of effects on lung vasculature have also been reported.
In humans, two large clinical trials, with several follow-up extensions involving thousands of patients, consistently showed that OFEV could reduce FVC decline by 50 percent in one year, and lower the risk of all-cause mortality by 30 percent.
The most frequently reported adverse effect of OFEV treatment was diarrhea — 62 percent versus 18 percent in the placebo group. Side effects related to diarrhea were mild to moderate, and only 5 percent of the patients decided to stop treatment due to adverse effects. More than 90 percent of patients in the first clinical trial chose to continue participating in the second trial.
The review concluded that OFEV reaches the established treatment goals of an effective therapy, as it can stop disease progression, reduce symptoms, prevent acute exacerbations, and prolong patient survival.
Current recommendations do not favor either OFEV or Esbriet, but rather emphasize the inclusion of patient values and preferences in treatment decisions. The choice of approved drug also needs to take potential side effects, comorbidities, and lifestyle factors into account.