Reata Pharmaceuticals recently announced the recruitment of the first patient with pulmonary hypertension associated with interstitial lung disease (PH-ILD) in their Phase 2 LARIAT clinical trial evaluating the efficacy, safety, and tolerability of experimental therapy bardoxolone methyl in the treatment of patients with pulmonary hypertension (PH). The recent enrollment is part of the expansion of the LARIAT study, whose first promising results were presented at the annual meeting of the American College of Chest Physicians (CHEST 2015). The study will now enroll patients with PH associated with certain types of interstitial lung disease and pulmonary fibrosis.
Bardoxolone methyl, an antioxidant inflammation modulator (AIM) drug, targets important inflammatory pathways involved in the regulation of the immune response and oxidative damage. In previous pre-clinical studies, it has been shown to inhibit NF-κB, a protein essential to the regulation of the immune response to infection. The faulty regulation of this protein, found to be increased in PAH, has been linked to processes such as inflammation and autoimmune responses. Bardoxolone methyl has also been shown to activate Nrf2, a protein involved in the regulation of antioxidant proteins with protective effects against inflammation and oxidative damage. Reata believes that the drug can potentially suppress reactive oxygen species (ROS) production, which are also involved in inflammatory processes in PAH. Furthermore, bardoxolone methyl has the potential to reduce fibrosis and attenuate the effects of mitochondrial damage found in PAH patients by increasing cellular respiration and energy production.
The LARIAT study (A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension) is a Phase 2 trial that aims to assess the tolerability, safety and efficacy of bardoxolone methyl relative to a placebo control group in patients with PAH on stable background therapy. The presentation at CHEST 2015 included positive results in patients from the WHO Group 1 PH (pulmonary arterial hypertension). The positive data on exercise capacity (assessed by 6 minute walk test), safety and tolerability, together with preclinical data, led to the inclusion of WHO Group 3 pulmonary hypertension patients with interstitial lung diseases [Connective tissue disease-associated (CTD-ILD), Idiopathic pulmonary fibrosis (IPF) and Nonspecific interstitial pneumonia (NSIP)] and WHO Group 5 pulmonary hypertension patients with sarcoidosis.
Colin Meyer, MD and Reata’s Chief Medical Officer commented on the announcement in a press release provided by Reata to Pulmonary Fibrosis News, “We are pleased to announce that we have quickly expanded our PH program into interstitial lung disease patients who have no approved therapies to treat their pulmonary hypertension. We hypothesize that bardoxolone methyl’s novel mechanism of action of improving mitochondrial function and suppressing inflammation can translate to improved functional capacity in PH patients with interstitial lung disease.”
For more information on the LARIAT trial and how to participate, please visit this link.