Recently, clinical-stage biopharmaceutical company Imara Inc. (“Imara”) announced that the first patient was dosed in the Phase 2b Forte clinical trial. The trial is evaluating IMR-687, a PDE9-inhibitor, for patients with beta thalassemia. Outside of this trial, Imara is also considering IMR-687 as a potential treatment for patients with sickle cell disease (SCD).
So what is IMR-687? This small molecule phosphodiesterase-9 (PDE9) inhibitor works by (you guessed it!) blocking PDE9. Generally, PDE9 degrades cyclic guanosine monophosphate (cGMP), which plays a role in vascular biology. Vascular means that it has to do with the system of blood vessels throughout your body. In addition to vascular benefits, PDE9 inhibitors have also been shown to improve cognitive function.
Patients with beta thalassemia, in addition to low hemoglobin levels, often also have low cGMP levels. This prevents proper blood flow and raises bodily inflammation. Additionally, it may contribute to the sickling (misshaping) of red blood cells. By inhibiting PDE9, IMR-687 raises hemoglobin levels, thus reducing symptoms.
Currently, there are no approved orally-administered treatment to raise fetal hemoglobin in patients with beta thalassemia. So this trial is designed to evaluate the safety, efficacy, and tolerability of IMR-687 for patients with this disorder. In preclinical trials, IMR-687 increased red blood cell production and maturation. Researchers hope to see similar results in the Phase 2b Forte trial.
Overall, the trial will enroll 120 participants. The group will be separated based on patients who require transfusions and those who do not. In the first group, researchers hope to understand how IMR-687 changes the amount of time in between needing transfusions. For the latter group, researchers will evaluate the impact of this therapy on hemoglobin levels and anemia.
There are three forms of beta thalassemia, a rare blood disorder characterized by reduced hemoglobin levels. These forms – minor, intermediate, and major – delineate the condition’s severity. Overall, beta thalassemia results from HBB gene mutations. This prevents the normalization of hemoglobin levels. Since hemoglobin, a part of red blood cells, carries oxygen throughout the body, lowered levels may cause many difficulties. An estimated 288,000 people worldwide have beta thalassemia. However, this condition is thought to be less prevalent in the United States and Europe. Symptoms include:
- Pale skin
- Abnormal spleen enlargement
- Difficulty breathing or shortness of breath
- Muscle weakness
- Blood clots
- Organ damage and failure
Learn more about beta thalassemia here.