Formulation and Standardization of a Sickle Cell Disease Drug for Clinical Trial

DESCRIPTION (provided by applicant): Sickle cell disease (SCD) is a hereditary blood disorder, affecting over 75,000 people in the United States and millions of people worldwide. In the US, those with SCD have an average mortality in their 40s, a poor quality of life and high medical costs. In SCD, a mutation in 2-globin causes deoxygenated sickle hemoglobin (deoxy-HbS) to form insoluble polymers inside red blood cells (RBCs), which deforms the RBCs into rigid shapes or sickle cells that occlude capillaries and small blood vessels. Despite the extensive studies of SCD by researchers over several decades, there has been little progress in the development of additional disease modifying agents beyond hydroxyurea. Therefore, new safer and more effective therapeutic antisickling agents are needed to treat patients with SCD, particularly children, which could improve the quality of life and increase the life expectancies of sufferers of this disease and reduce the estimated 500 million in direct hospital costs. A dried extract of four plants has been used to treat patients with SCD in Nigeria for many years (NIPRISAN). It has been through multiple clinical trials in Nigeria and has been formally approved for use in that country since 2006 for the treatment of SCD. The US FDA has determined there is sufficient safety and efficacy data for NIPRISAN to start a Phase III clinical trial. The US FDA Botanical Review Team (BRT) suggested a simpler formulation of NIPRISAN, development of a chemical fingerprint for the formulation using LC/MS and elucidation of some of the anti-sickling compounds in the formulation would improve standardization and increase the probability of obtaining FDA marketing approval. Our long-term goal is to produce a new drug to treat SCD. The goal of the Phase II proposal is to fund Phase I/II clinical trials in patients with SCD. The Phase I hypothesis of this research is that a standardized formulation of this botanical is possible. Specific Aims: Produce a simpler botanical formulation of NIPRISAN and define a LC/MS chemical fingerprint for the botanical. Identify anti-sickling compounds in the mixture of botanicals that can help in standardization of the botanical formulation and provide leads for new synthetic antisickling compounds for future development as clinical candidates. File an IND for the botanical formulation. Commercial Opportunity: A safer and more effective drug to treat SCD is desperately needed, particularly in children. There are 75,000 to 100,000 SCD patients in the US, 50,000 SCD patients in Europe and many million world-wide. There are no other drugs that modify this disease besides hydroxyurea. Therefore, there is a large unmet medical need for another disease modifying drug. PUBLIC HEALTH RELEVANCE: About 75,000 Americans have Sickle Cell Disease. Those affected often have high medical costs, a poor quality of life, and early death. Treatment options are few. There is a substantial unmet medical need for new safe and effective disease modifying drugs, like the one in this grant, to treat this disease.