Patients Being Enrolled for Phase 2 and 3 Trials of Bardoxolone Methyl to Treat PAH and PH
Reata Pharmaceuticals is enrolling participants for two ongoing clinical trials of bardoxolone methyl as a treatment for pulmonary arterial hypertension (PAH) and pulmonary hypertension (PH) caused by an underlying interstitial lung disease.
Bardoxolone methyl belongs to a class of small molecules that target an important transcription factor called Nrf2. A transcription factor is a protein that controls the rate at which genetic information in DNA is converted to messenger RNA, a process that helps regulate gene expression. Genes use expression to create a functional product like a protein.
Activating Nrf2 can restore normal mitochondrial function, preclinical-trial studies have indicated. Mitochondria are cell components that convert food to energy and promote an increase in cells’ antioxidant content.
Because almost all cell pathways are interconnected, converting food into energy and increasing cells’ antioxidant content reduce reactive oxygen damage and inflammation. This, in turn, can reduce fibrosis.
By targeting this complex cascade of signals, bardoxolone methyl could affect cell mechanisms involved in creating fibrosis, or tissue scarring. The overarching result would be to increase PH patients’ ability to function.
Reata is testing bardoxolone methyl in Phase 2 and 3 clinical trials, according to a press release. The Phase 2 LARIAT trial (NCT02036970) is evaluating it as a treatment for PAH and pulmonary hypertension stemming from an interstitial lung disease (PH-ILD). The Phase 3 CATALYST trial (NCT02657356) is assessing it as a treatment for PAH associated with connective tissue disease (CTD-PAH). Both studies are still recruiting participants.
The LARIAT trial will be divided into two parts. The first stage will address dose and tolerability, and the second the treatment’s long-term safety and effectiveness. Reata plans to enroll about 200 patients with PH-ILD caused by sarcoidosis, idiopathic pulmonary fibrosis, CTD, and idiopathic interstitial pneumonia.
The company expects LARIAT results to be available in the second half of 2017.
The main objective of the CATALYST study is for bardoxolone methyl to improve a measure of patients’ exercise capacity called the six-minute walk distance, in comparison with placebo-treated patients.
CATALYST enrolled its first patient in October 2016. The 24-week trial is expected to recruit between 130 and 200 participants. It will evaluate bardoxolone methyl’s effectiveness, safety and tolerability. Patients will receive the therapy once a day.
Another CATALYST goal is for the treatment to reduce the time it takes patients to see their first signs of physical improvement. And a third goal is to reduce by at least 10 percent their levels of muscle-injury and inflammation biomarkers, such as creatine kinase levels.
Interim results from the CATALYST study are expected during the first half of 2018, Reata said.