Rigel Pharmaceuticals has announced the enrollment of the first patient in a Phase I clinical trial evaluating fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of sickle cell disease (SCD). The trial, sponsored by the National Heart, Lung, and Blood Institute (NHLBI), a part of the National Institutes of Health (NIH), aims to assess the safety and tolerability of fostamatinib in patients with this debilitating condition.
Fostamatinib, already marketed as TAVALISSE® in the US for chronic immune thrombocytopenia (ITP), is now being investigated for its potential to mitigate complications associated with SCD, including severe pain episodes, strokes, and organ dysfunction. This collaboration between Rigel and the NIH/NHLBI marks a significant step in exploring new therapeutic avenues for SCD, a disease affecting over 100,000 individuals in the United States and millions globally.
Rationale for SYK Inhibition in SCD
Dr. Richard Childs, scientific director at NHLBI, highlighted preclinical research suggesting that SYK inhibition, the mechanism of action of fostamatinib, could alleviate complications related to red blood cell sickling and thrombo-inflammation in SCD patients. "Our Phase I study evaluating fostamatinib in patients with sickle cell disease is an opportunity to explore a potential new treatment option for a disease that is associated with a high degree of recurrent acute pain events and other acute and chronic potentially life-threatening complications," said Childs.
Study Design and Objectives
The Phase I study plans to enroll approximately 20 patients with SCD. Led by Dr. Swee Lay Thein, senior investigator and chief of the Sickle Cell Branch at NHLBI, the trial will administer escalating doses of fostamatinib. Patients will initially receive 100 mg twice daily for 14 days, with a potential increase to 150 mg twice daily for an additional 28 days, contingent on tolerability.
The primary objective of the study is to evaluate the safety and tolerability of fostamatinib in this patient population. Secondary and exploratory endpoints include assessing the drug's effects on the underlying mechanisms of SCD, such as red blood cell membrane stability, sickling kinetics, and platelet activation. Researchers will also investigate fostamatinib's potential impact on neutrophil activation and the formation of neutrophil extracellular traps (NETs), which play a crucial role in the inflammatory processes of SCD.
The study is being conducted at the NIH Clinical Center in Bethesda, Maryland, with Rigel Pharmaceuticals providing the study material. Raul Rodriguez, president and CEO of Rigel, expressed enthusiasm for the study, stating, "We are excited to support another important study conducted by the NIH/NHLBI for fostamatinib, as they investigate SYK inhibition and its potential to benefit patients with sickle cell disease."
Potential Impact on SCD Treatment
If successful, this Phase I trial could pave the way for future studies exploring the broader potential of SYK inhibitors in hematologic and other inflammatory disorders. The current study focuses on an area of critical unmet need and contributes to Rigel's mission to improve the lives of patients with hematologic disorders and cancer.
Sickle cell disease (SCD) is a genetic hemoglobinopathy that leads to the production of abnormal hemoglobin, the protein that carries oxygen through the body. Normally, red blood cells are disc-shaped and flexible enough to move easily through the blood vessels. In sickle cell disease, red blood cells become rigid and crescent – or “sickle” – shaped, leading to strokes, infections, vaso-occlusive crises and multi-organ dysfunction. The condition affects more than 100,000 people in the United States and an estimated 7-8 million people worldwide.
