Initial Results for Phase 2 Bardoxolone Methyl Study For PAH to be Presented in October

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by Maureen Newman |

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Preliminary results for the Phase 2 LARIAT clinical trial conducted by Reata Pharmaceuticals for bardoxolone methyl in pulmonary arterial hypertension will be presented at the upcoming 2015 American College of Chest Physicians (CHEST) annual meeting in Montreal, Canada. Ronald Oudiz, MD, Professor of Medicine in David Geffen School of Medicine at UCLA, will present, “Initial Data Report from ‘LARIAT’: a Phase 2 Study of Bardoxolone Methyl in PAH Patients on Stable Background Therapy.”

“We are excited to present top‐line data from our Phase 2 LARIAT study,” said Colin Meyer, MD, Chief Medical Officer of Reata Pharmaceuticals, in information provided to Scleroderma News. “Bardoxolone methyl has the potential to be a first‐in‐class treatment for PAH that impacts aspects of the disease that are unaddressed by current therapies, including inflammation and mitochondrial dysfunction. Clinically, these manifest as markedly reduced exercise capacity and fatigue, despite optimal treatment with available therapies.”

Pulmonary hypertension, often times the result of thickened pulmonary artery walls in patients with scleroderma, is usually treated with vasodilators. Since the vessel walls are thickened and the diameter of the vessels is narrowed, the theory behind treatment with vasodilators is that the diameter of the vessels will increase, allowing blood to flow through more easily and reduce the pressure in the pulmonary arteries. That way, when the heart pumps blood to the lungs for oxygenation, the heart has less pressure to work against.

Sound in theory, vasodilators sometimes work to help patients, but not all patients see benefits. Reata Pharmaceuticals recognized that other treatments aside from vasodilators must exist, and researchers at the company have been working to develop bardoxolone methyl, an antioxidant inflammation modulator (AIM). Working through a natural antioxidant pathway within cells, bardoxolone methyl permits gene transcription to produce anti-inflammatory mediators and enhance antioxidant capacity in cells. Additionally, bardoxolone methyl promotes proper mitochondrial function to reduce the amount of harmful oxidative species generated in the mitochondria that could otherwise contribute to cell damage and inflammation.

“In preclinical models, we have demonstrated that bardoxolone methyl directly improves mitochondrial function and energy production in the skeletal muscle while not affecting systemic hemodynamics,” said Dr. Meyer. “This profile is unique and should complement available therapies, all of which have primary vasodilatory effects.”

The current results of LARIAT will include data from three initial cohorts of patients, or 24 patients in total. They were treated with bardoxolone methyl for 16 weeks and were evaluated for six-minute walk distance (6MWD) every four weeks. These patients all had stable pulmonary hypertension and were on at least one approved pulmonary arterial hypertension therapy so that researchers can see how bardoxolone methyl compliments other therapies.

Reata Pharmaceuticals is also branching out to pulmonary hypertension caused by interstitial lung disease. In interstitial lung disease, lung tissue shows signs of scarring, and the matrix around cells is thickened and stiff. This disallows air sacs from expanding to their full potential and also presses on the pulmonary vessels to restrict blood flow. “On the basis of the emerging preclinical and clinical data, we are further expanding our development program and plan to study bardoxolone methyl in other forms of pulmonary hypertension, including pulmonary hypertension caused by interstitial lung disease,” said Dr. Meyer.