Highlights from

EHA 2019

European Hematology Association

Amsterdam 13-16 June 2019

Positive initial data evaluating the safety and efficacy of IMR-687 for treatment of sickle cell disease

Promising 13-week interim phase 2a data on IMR-687 in patients with sickle cell disease (SCD) were presented by Dr Biree Andemariam (UConn Health, USA). Treatment with IMR-687 in adult patients was generally well tolerated. The data also support the dual mechanism of action of IMR-687, with activity seen across both red and white blood cell biomarkers.

IMR-687 is an investigational, orally administered, selective phosphodiesterase 9 (PDE9) inhibitor. Dr Andemariam explains: "In the laboratory we saw that IMR-687 inhibition of PDE9 increases intracellular cGMP levels, increases foetal haemoglobin expression, reduces sickling and haemolysis of red blood cells, and does not induce neutropenia. The interim phase 2a data reflect trends that could be indicative of meaningful clinical translation of these important measures in SCD."

The phase 2a clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating doses of IMR-687 administered once daily for 16 to 24 weeks in 2 groups of patients with SCD: those not on hydroxyurea (HU) (Population A) and those receiving a stable dose of HU according to the current standard of care (Population B). Blinded white cell markers in Population A (n=19), along with red cell markers and quality of life measures (ASCQ-Me) (n=13) were analysed. The blinded interim analysis was conducted on the monotherapy IMR-687 (Population A) subgroup. At 5 weeks, in the 100 mg dose group of Population A, there was a trend to reduced soluble P selectin (sPsel), soluble vascular cell adhesion molecule-1 (sVCAM), and myeloperoxidase (MPO) compared with placebo. At 13 weeks, the 100 mg dose group of Population A saw an increase (110%) in the percent of F cells, which are red blood cells that contain foetal haemoglobin (HbF) that often precede rises in total HbF. A corresponding decrease in absolute reticulocyte count and the percentage of reticulocytes, with a trend towards improved pain as measured by ASCQ-Me, was also observed at 13 weeks in Population A.

Blinded safety data for 27 patients demonstrated good tolerability, with no clinically significant changes in white blood cell counts and no evidence of neutropenia. There were no treatment-related serious adverse events.

  1. Andemariam B, et al. Abstract S854, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.