Imara Inc. announced results from interim analyses of its Ardent Phase 2b clinical trial of tovinontrine (IMR-687) in patients with sickle cell disease (SCD) and Forte Phase 2b clinical trial of tovinontrine in patients with beta-thalassemia. Imara also announced that because of the data generated by these interim analyses, the company will discontinue the Ardent and Forte trials as well as the further development of tovinontrine in sickle cell disease and beta-thalassemia. Ardent Phase 2b Sickle Cell Disease Interim Analysis: The interim analysis for the Ardent trial was conducted when all participants completed the week 24 assessment or terminated early.

The intent-to-treat (ITT) population was used for the primary efficacy analysis, which is a comparison of the median annualized vaso-occlusive crisis (VOC) rate between the high dose tovinontrine group (n=47, once daily oral dose of 300 mg or 400 mg based on patient weight) and placebo group (n=32). Safety was analyzed across all participants enrolled in the Ardent trial, including the high dose, low dose (n=33, 200 mg or 300 mg once daily oral dose based on patient weight) and placebo groups. Data from the interim analysis demonstrated that tovinontrine was generally well-tolerated, with the most frequent adverse events (=10% of participants in any treatment group) considered at least possibly related to study drug by the investigator being nausea, headache, dizziness and vomiting.

Four (3.6%) participants discontinued prior to week 24 due to adverse events. The median annualized VOC rate in the placebo group was 2.02 VOCs per year and was 1.89 VOCs per year in the high dose tovinontrine group, for a treatment difference of 0.13 VOCs per year, or 6.4%. Based on the minimal decrease observed in VOCs with the high dose and low VOC rate in the placebo arm, Imara enacted an addendum to the statistical analysis plan for the trial and noted trends of VOC benefit with tovinontrine.

The median annualized rate of VOCs in the low dose tovinontrine group was zero, as compared to 2.02 in the placebo group, and as compared to placebo, the low dose tovinontrine group experienced an increase in median time to first VOC and a higher proportion of participants who were VOC-free. A trend for lower median annualized rate of VOCs was also observed for participants in the high and low dose tovinontrine groups on monotherapy (not on background hydroxyurea) as compared to placebo. Although these additional data are encouraging, none were statistically significant.

In addition, no meaningful difference was observed in fetal hemoglobin (HbF) response in either the high or low dose tovinontrine groups as compared to placebo. Collectively, the overall additional data did not materially increase the likelihood of success for this trial.