In Part 2 of the Phase 2 MOXIe study of omaveloxolone in patients with Friedreich’s ataxia, a rapid, continuous decline in kidney function as measured by eGFR was observed in the placebo group. Omaveloxolone treatment for 48 weeks was associated with an increase in eGFR. These increases were durable and sustained throughout one year of treatment, similar to results observed with its analog, bardoxolone methyl, in clinical trials for various forms of CKD.
- The rate of eGFR decline in patients with FA was equal to or greater than many forms of CKD.
- Rapidly progressive loss of kidney function in patients without traditional risk factors for CKD highlight the role of mitochondrial dysfunction in progression of CKD.
- Placebo-corrected increases in patients treated with omaveloxolone were durable through one year of treatment.
Omaveloxolone and novel Nrf2 activator TX63682 decreased hepatic fat deposition, hepatocellular ballooning, hepatic inflammatory cell infiltration, nonfasting blood glucose and glycated hemoglobin A1C concentrations, and liver and serum triglycerides in the STAM mouse model of nonalcoholic steatohepatitis (NASH).
- Omaveloxolone and TX63682 demonstrated significant hepatoprotection in a rodent model of NASH in conjunction with improvements in glucose control and lipid handling, which is consistent with the overall phenotype of improved mitochondrial function that is associated with Nrf2 activation.
- Mild increases in serum transaminases were observed in conjunction with improvements in hepatic histology and without major changes in serum bilirubin suggesting that they are a pharmacological and not toxic effect.
- Overall, these data suggest that changes in serum chemistries and other blood based markers observed with our Nrf2 activators are likely a pharmacologic effect of Nrf2 activation associated with restoration of lipid metabolism and suppression of inflammation.
Reata announced that the registrational Part 2 portion of the MOXIe Phase 2 trial of omaveloxolone in patients with Friedreich’s ataxia met its primary endpoint of change in the modified Friedreich’s Ataxia Rating Scale (mFARS) relative to placebo after 48 weeks of treatment.
- Part 2 of MOXIe, an international, multi-center, double-blind, placebo-controlled, randomized registrational Phase 2 trial, enrolled 103 patients with FA.
- Omaveloxolone treatment met the primary endpoint of the study producing a statistically significant, placebo-corrected 2.40 point improvement (decrease) in mFARS (n=82; p=0.014).
- Omaveloxolone was generally reported to be well tolerated in this study.