Ligand Pharmaceuticals Incorporated is initiating phase I clinical trials of LGD 4665, an oral, small molecule drug that mimics the activity of thrombopoietin (TPO), a growth factor that promotes growth and production of blood platelets.

Thrombocytopenia or low platelet count is a common clinical finding associated with a diverse group of clinical disorders or conditions affecting platelet production and survival. Prevalent clinical disorders where platelet loss or dysfunction leads to significant morbidity include idiopathic thrombocytopenia purpura (ITP), myelodysplastic syndrome, liver dysfunction associated with hepatitis C viral and severe cirrhosis, chemotherapy-induced thrombocytopenia (CIT) as well as a number of other disorders. Current therapeutic options are mostly palliative, including steroids, immunosuppresants, splenectomy and, for the most severe thrombocytopenias, platelet transfusion.

Thrombopoietin (TPO) is the key hematopoietic growth factor responsible for platelet production. There are currently no approved TPO molecules available but there are both peptides and oral TPO mimetics in late-stage clinical development, the latter class including molecules developed by GSK in collaboration with Ligand.

While the size of the emerging thrombopoietin market is difficult to estimate, previous published estimates in research analyst reports at Merrill Lynch and Lehman Brothers suggest the potential worldwide market could be between $2.5 and $4.5 billion dollars per year.

LGD 4665 was selected from a group of novel oral TPO mimetics synthesized at Ligand, for which Ligand has retained exclusive worldwide rights. These molecules were profiled to have in vitro efficacy and selectivity equal to or better than TPO in predictive human cell models and to have a better profile for efficacy and potency than other oral mimetics currently in clinical development.

"We are very pleased that LGD 4665, a novel, second generation, orally active thrombopoietin mimetic is advancing to human clinical trials," said Andres Negro-Vilar, MD, PhD, executive vice president, R&D and chief scientific officer, Ligand Pharmaceuticals. "LGD 4665 has shown an excellent profile of activity in preclinical studies, and has the potential to become, in terms of efficacy, potency and selectivity, a competitive molecule for the treatment of different forms of thrombocytopenias. Potential disease targets under consideration by Ligand for advanced clinical development include idiopathic thrombocytopenia purpura (ITP), myelodysplastic syndrome and leukemias, platelet dysfunction associated with hepatitis C and chronic liver disease and chemotherapy-induced thrombocytopenia, among others."

"LGD 4665 targets a number of platelet disorders of different etiologies, in what represents an underserved, large pool of patients frequently requiring long-term treatment for chronic, debilitating conditions associated with platelet loss and dysfunction," said Andres Negro-Vilar, MD, PhD.

Ligand discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, pain, skin diseases, men's and women's hormone-related diseases, osteoporosis, metabolic disorders, and cardiovascular and inflammatory diseases. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IRs).