Imara Discontinues Development of Tovinontrine after Disappointing Results in Sickle Cell Disease and Beta Thalassemia
April 5, 2022
Imara said it would discontinue development of tovinontrine in sickle cell and beta thalassemia after reporting disappointing results from interim analyses of its Ardent phase 2b clinical trial in patients with sickle cell disease and Forte phase 2b clinical trial in patients with beta thalassemia.
Sickle cell disease (SCD) and beta thalassemia are both genetic hemoglobinopathies that affect the ability of the blood to deliver oxygen to the cells throughout the body. In SCD, mutated hemoglobin causes the red blood cells to develop a sickle shape that impedes their flow through the body, causing anemia, pain crises, organ failure, and early death. Beta thalassemia, caused by a mutation in the HBB gene, reduces the production of hemoglobin, the iron-containing protein in red blood that carries oxygen to cells, leading to a lack of oxygen in many parts of the body.
Tovinontrine is a highly selective and potent small molecule inhibitor of phosphodiesterase-9 (PDE9) with a multimodal mechanism of action that acts on red blood cells, white blood cells, adhesion molecules and blood vessels. PDE9 selectively degrades cyclic guanosine monophosphate (cGMP), an active signaling molecule that plays a role in vascular biology.
Interim results in the Ardent trial for sickle cell disease showed no significant difference in median annualized rate of vaso-occlusive crises in high-dose group versus placebo in an intent-to-treat population. Interim results in the Forte trial for beta thalassemia demonstrated no meaningful benefit in transfusion burden or improvement in most disease-related biomarkers. Tovinontrine was generally well-tolerated across both studies.
“We are disappointed in the outcome of both of the interim analyses in our phase 2b studies for sickle cell disease 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, president and CEO of Imara. “We plan to discontinue both studies during the second quarter. Moving forward, we plan to consider our strategic options, including development of tovinontrine in heart failure with preserved ejection fraction (HFpEF) as well IMR-261 clinical development plans.”
Author: Rare Daily Staff
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