Imara Completes Patient Enrollment for Ardent Trial Testing IMR-687
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Imara has completed patient enrollment for its Phase 2b Ardent clinical trial, which is testing the safety and efficacy of IMR-687 for the treatment of sickle cell disease (SCD).
“We are excited to have enrolled [participants] from across the world, including in Africa, making this a truly global effort,” Rahul Ballal, PhD, president and CEO of Imara, said in a press release.
The Ardent trial (NCT04474314) had sought to recruit an estimated 99 patients with SCD from 50 clinical sites across 13 countries worldwide. Interim data is expected by the end of 2021.
“We are pleased to achieve this important milestone for IMR-687,” Ballal said. “We look forward to reporting interim data for the Ardent trial in the fourth quarter of this year and can now refine guidance and expect to report data from the primary analysis in the first quarter of 2022.”
IMR-687 (tovinontrine) is a highly selective oral inhibitor of phosphodiesterase 9 (PDE9), an enzyme that destroys cyclic guanosine monophosphate (cGMP), an important active signaling molecule. In people with SCD, cGMP levels are typically low and associated with impaired blood flow and increased inflammation.
By blocking PDE9 and increasing the levels of cGMP, IMR-687 is expected to restart the production of fetal hemoglobin, a form of hemoglobin (Hb) produced during fetal development. The substance that gives color to red blood cells, hemoglobin helps in the transport of oxygen throughout the body.
According to the company, increased levels of fetal Hb — which is a more efficient transporter of oxygen than adult Hb — in red blood cells can ease the symptoms of sickle cell disease.
The ongoing Ardent trial is assessing the safety and efficacy of IMR-687 in adults, ages 18–65, with SCD. After enrollment, participants are randomly assigned to receive either a low (200 mg or 300 mg) or high (300 mg or 400 mg) dose, based on patient weight, of IMR-687, or a placebo, once per day for one year.
The trial’s main goal is to evaluate the proportion of patients having an increase of at least 3% in the production of fetal Hb after about six months of treatment. Secondary goals entail assessing the treatment’s effects on the levels of several biomarkers associated with fetal Hb, the rate of red blood cells’ destruction (hemolysis), the incidence of pain crises, and quality of life.
Before Ardent, Imara investigated IMR-687’s safety and pharmacological properties in a Phase 2a trial (NCT03401112) in the U.K. and the U.S. Results from the first and second analyses showed that IMR-687 lowered the levels of different disease biomarkers and increased the number of red blood cells with fetal Hb.
In addition, six months of treatment with IMR-687 also reduced the number of vaso-occlusive crises and other disease-related pain crises in SCD patients. The therapy was generally well-tolerated and safe, the trial data also indicated.
IMR-687 was granted orphan drug, fast track, and rare pediatric disease designations by the U.S. Food and Drug Administration. In August 2020, it received orphan drug status from the European Commission as a potential treatment for SCD. These designations all are intended to accelerate IMR-687’s development to get it to patients more quickly, if it is approved.
Imara also announced that the United States Adopted Names (USAN) Council adopted “tovinontrine” as the generic name for IMR-687.
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