Imara Doses First Patient in Phase 2a Clinical Trial of IMR-687 for Sickle Cell Disease
- Category: Small Molecules
- Published on Tuesday, 13 February 2018 17:50
- Hits: 323
- Unique mechanism-of-action shown in preclinical studies to impact red and white blood cell pathologies associated with this disease
- First clinical trial sites open in the United Kingdom; additional sites opening in the United States
CAMBRIDGE, MA, USA I February 13, 2018 I Imara Inc. today announced it has dosed the first patient in its Phase 2a clinical trial, evaluating the safety, pharmacokinetics and pharmacodynamics of escalating doses of IMR-687 in adult patients with sickle cell disease (SCD). IMR-687 is a highly potent and selective inhibitor of phosphodiesterase-9 (PDE9i) in blood cells. IMR-687 is designed as an oral therapy for once-daily dosing to address both the underlying red and white blood cell pathologies associated with SCD.
“As part of our commitment to bringing a transformative new treatment to patients in need, we are rapidly advancing IMR-687 – we are dosing our first sickle cell patient less than two years from launching Imara,” said James McArthur, Ph.D., Founder, President, and Chief Executive Officer of Imara. “Based on the data to date, we believe IMR-687 has the potential to dramatically improve the lives of patients with SCD by reducing red blood cell sickling and red blood cell lysis, reducing white blood cell adhesions, thus ultimately reducing vaso-occlusive crisis and hospitalizations.”
This randomized, double-blind, multi-center Phase 2a study of IMR-687 will evaluate the safety, pharmacokinetics and pharmacodynamics of escalating doses of IMR-687 as compared to placebo in adult patients with sickle cell disease. The trial will also expand to include adults on a stable dose of hydroxyurea (HU; also known as hydroxycarbamide), which up to 25-35% of patients with SCD are estimated to be prescribed. Approximately 50 patients will be enrolled at several clinical trial centers in the United Kingdom and the United States.
“The current disease-modifying strategies in sickle cell disease are hydroxycarbamide, blood transfusions and, for a few, haematopoietic stem cell transplant. For the majority of patients, the mainstay of treatment is supportive,” said Dr. Shivan Pancham of Sandwell and West Birmingham Hospitals, an investigator in the study. “Newer agents that have been developed based on the greater understanding of the pathophysiology of sickle cell disease have the potential to become new treatment options needed for this condition.”
There remains a significant unmet need for patients with SCD. The majority of patients with SCD are treated only with pain medications, fluids, and blood transfusions; many experience frequent hospitalizations as a result. The only approved treatments for SCD are hydroxyurea, approved more than a decade ago, and L-glutamine oral powder. Bone marrow or stem cell transplants may be an option for younger patients with severe SCD. However, these treatment options either come with severe and potentially life-threatening side effects or have limited efficacy.
Further information on this study can be found on https://www.clinicaltrials.gov/ under the study ID number NCT03401112.
IMR-687 was designed to address the underlying pathology of sickle cell disease. An orally-administered, highly-potent and selective phosphodiesterase 9 (PDE9) inhibitor, IMR-687 is a potentially disease-modifying therapeutic for sickle cell disease as well as other hemoglobinopathies. Pre-clinical data demonstrate IMR-687 reduces both the sickling of red blood cells and blood vessel occlusion that cause debilitating pain, organ damage, and early mortality in affected patients. A Phase 1 clinical trial in healthy volunteers showed IMR-687 to be safe and well-tolerated.
IMR-687 has been granted both U.S. Orphan Drug Designation and U.S. Rare Pediatric Designation by the Food and Drug Administration (FDA).
About Sickle Cell Disease
Sickle cell disease is a rare, genetically inherited condition that alters hemoglobin, the protein in red blood cells that transports oxygen throughout the body. The altered hemoglobin distorts red blood cells into a stiff, inflexible crescent shape, known as a “sickle”. Painful episodes can occur when sickled red blood cells get stuck in small blood vessels. These episodes deprive tissues and organs of oxygen-rich blood and can lead to vaso-occlusive crisis (VOC), acute chest syndrome (ACS), and permanent damage to organs including the liver, spleen, kidney and brain.
Imara Inc., a Cydan Development company, is dedicated to developing novel therapeutics for patients with sickle cell disease. Imara is developing IMR-687, a highly selective, potent small molecule inhibitor of PDE9, to treat patients with sickle cell disease. The company was launched following an 18-month diligence and de-risking scientific collaboration between orphan drug accelerator Cydan Development and H. Lundbeck A/S with $31M Series A funding from life science investors NEA, Pfizer Venture Investments, Lundbeckfonden Ventures, Bay City Capital and Alexandria Venture Investments.