IPF Review Study Focuses on Effectiveness of OFEV

Magdalena Kegel avatar

by Magdalena Kegel |

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IPF treatment

A new article that reviews available treatment options for idiopathic pulmonary fibrosis (IPF) took aĀ 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’sĀ pharmacological characteristics.

The article, titled Idiopathic pulmonary fibrosis: current treatment options and critical appraisal of nintedanibĀ byĀ Francesco Bonella and colleagues from theĀ University of Duisburg-Essen, Germany, in collaboration withĀ Boehringer Ingelheim, was published in the journalĀ 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 toĀ the market, revolutionizing IPF treatment. One of them is OFEV (nintedanib) byĀ Boehringer Ingelheim.

The goal of current IPF treatment is to stop disease progression,Ā reduce symptoms and prevent acute exacerbations, with the ultimate long-term goal of prolonging survival. The review states that all careĀ ā€” whetherĀ preventive, rehabilitative, or based on symptom treatment ā€” needs to be started early to minimize the decline in quality of life that follows diagnosis.Ā 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 subjectĀ 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.Ā 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 thatĀ N-acetylcysteine, the previous common treatment,Ā had no effect on forced vital capacity (FVC), a measure of lung function, in IPF patients.

Both OFEV and Esbriet are antifibrotic drugsĀ 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 theĀ clinical trials leading to the approval of the two drugs includedĀ slightly different groups of patients, a direct comparison between the trials is not possible.

There also have not been anyĀ 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 wereĀ studied in bothĀ in vitroĀ 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 ā€” a cell type contributing to fibrosis development ā€” by inhibiting TGF-Ī². Some data also showed that OFEV can reduce the secretion of extracellular matrix components.Ā Studies on animal models of lung fibrosisĀ 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 byĀ 30Ā percent.

The most frequently reported adverse effect of OFEV treatment was diarrhea ā€” 62 percent versus 18 percent in the placebo group. Side effects relatedĀ to diarrhea were mild to moderate, and only 5 percent of the patients decidedĀ 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,Ā reduce symptoms, prevent acute exacerbations, andĀ prolong patient survival.

Current recommendations do not favor eitherĀ OFEV orĀ Esbriet, but rather emphasize the inclusion of patient values and preferences in treatment decisions. The choice of approvedĀ drug also needs to take potential side effects, comorbidities, and lifestyle factors into account.