Imara announced disappointing interim analysis results in the Ardent phase 2b clinical trial of tovinontrine in patients with sickle cell disease (SCD), as published in their press release. The lack of meaningful benefits from the treatment will result in the discontinuation of the trial, as well as ceasing the development of tovinontrine, a highly selective and potent phosphodiesterase-9 inhibitor.
“We are disappointed in the outcome of both of the interim analyses in our Phase 2b studies for [SCD] and beta-thalassemia, and particularly that the Ardent trial interim analysis did not replicate our previously observed positive vaso-occlusive crisis data,” said Rahul Ballal, PhD, president and chief executive officer of Imara. “We plan to discontinue both studies during the second quarter.”
Read more about SCD treatment
Both trials were randomized, double-blind, placebo-controlled, multicenter phase 2b studies on adult patients with SCD. In the Ardent trial, the interim analysis was conducted at week 24 and the median annualized vaso-occlusive crisis rate between a high-dose tovinontrine group and placebo was compared.
The safety of the drug was also analyzed between high-dose, low-dose, and placebo groups. While the medication was generally well-tolerated, no significant differences in vaso-occlusive crises were observed between the groups.
In the Forte trial, safety and biomarker data were assessed for 2 cohorts, transfusion-dependent thalassemia and nontransfusion-dependent thalassemia. In addition, transfusion burden reduction in the transfusion-dependent thalassemia cohort was evaluated. Again, tonivontrine was well tolerated by the patients, but no meaningful benefit was achieved in either transfusion burden or disease-related biomarkers.
Tovinontrine will still be developed for patients with heart failure with preserved ejection fraction, according to the company.
Imara announces results of interim analyses of tovinontrine (IMR-687) phase 2b clinical trials in sickle cell disease and beta-thalassemia. News release. Imara; April 5, 2022.