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IMR-687 is classified as a phosphodiesterase 9 (PDE9) inhibitor. By blocking selective phosphodiesterase inhibitors, PDE9s increase cellular adenosine monophosphate (cAMP) and cellular adenosine triphosphate (cATP), allowing cells to function in ways previously inhibited.

Before clinical testing, IMR-687 was shown to reduce erythrocyte sickling in vitro. In patients treated with IMR-687, fetal hemoglobin levels increased when doses of the drug were increased at four weeks, although no meaningful increases in fetal hemoglobin were seen after six months.

During its first 13 weeks of a 2a trial, the drug was well tolerated and reduced signs of sickle cell disease in both red and white blood cells. In January of 2021, Sickle Cell News reported that IMR-687’s 2a trial continued to show success. After six months of treatment, patients showed significantly lower risk of vaso-occlusive crises and pain.

A total of 58% of patients treated with IM-687 experienced vaso-occlusive episodes or pain crises, compared with 83% of those given placebos. Among treated patients, 33% were hospitalized for vaso-occlusive diseases, versus 66% of patients taking placebo.

Markers of inflammation and cardiac stress also showed possible benefits of the drug for treating heart disease associated with sickle cell disease. The safety profile is also good. Common side effects included headache and nausea.

The medication is given once daily by mouth. At 200 mg per day, the highest dose, patients experience the greatest reduction in red blood cell destruction, inflammation, and heart stress. In June of 2021, further information on this ongoing study will be presented at an upcoming medical conference [1].

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[1] Reports, C. (2019, June 20). Sickle Cell Drug Showing Promise in Clinical Trial. UConn Today. https://today.uconn.edu/2019/06/sickle-cell-drug-showing-promise-clinical-trial/#

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