Acromegaly is an endocrine disorder caused by a benign pituitary tumor that affects approximately 25,000 adults in the US. Left untreated, the average life expectancy is 10 years from diagnosis. It is characterized by excess skeletal growth, soft-tissue enlargement, and permanent disfigurement, accompanied by metabolic dysfunction resulting from excess growth hormone secreted by the tumor. The disease is associated with 2- to 3-fold increased mortality and serious health complications and comorbidities. These include cardiovascular disease, which is responsible for approximately 50% of acromegalic deaths, respiratory disorders, which represent the second leading cause of death, and metabolic diseases such as type 2 diabetes and impaired lipid metabolism that contribute to greater cardiovascular risk and mortality. The broad consensus is that effective treatment is achieved by strict hormone control, demonstrated by the beneficial effects on comorbidities and mortality. When surgery either fails to completely remove the tumor or is not an option, medical therapy is required for long-term hormone control. However, control is achieved in only half of patients by the existing therapies. There is a clear unmet medical need for a therapy that achieves long-term hormone control consistently across the acromegaly patient population. Elixeras goal is to develop a novel therapeutic as a first- in-class treatment of acromegaly that fulfills this unmet medical need. The aim of the Phase 1 grant to identify and characterize new product leads. The aim of the Phase 2 grant is to have a therapeutic candidate ready for manufacture for an IND application with the FDA that will permit clinical trial testing in acromegaly patients in the US.
Public Health Relevance Statement: Project narrative: Acromegaly is a rare but potentially lethal disorder of the endocrine system caused by a benign tumor in the pituitary gland that produces excess growth hormone. There is an unmet medical need for treatment that can control the hormone levels consistently across the patient population. Elixera is developing a novel therapeutic for treatment of acromegaly that is intended to meet this need.
Project Terms: Acromegaly; Address; Adult; Affect; Affinity; Alloys; Antibodies; Antibody Therapy; base; Benign; Binding; Biological Assay; Cardiovascular Diseases; cardiovascular risk factor; Cause of Death; cell bank; Cell Line; Cells; Cessation of life; Clinical; Clinical Trials; Cloning; comorbidity; Consensus; Data; Data Analyses; Diagnosis; Disease; Dose; drug candidate; effective therapy; Endocrine system; Endocrine System Diseases; Epitopes; Genetic Engineering; Goals; Grant; Growth; growth hormone deficiency; Growth Hormone Receptor; Head; Health; Hormone secretion; Hormones; Human; human monoclonal antibodies; Hybridomas; Impairment; improved; In Vitro; in vitro activity; in vivo; in vivo Model; innovation; Insulin-Like Growth Factor I; Lead; lead candidate; lead optimization; lead series; Left; Libraries; Life Expectancy; lipid metabolism; manufacturability; Medical; Metabolic Diseases; Metabolic dysfunction; Modeling; Monoclonal Antibodies; mortality; neonatal Fc receptor; neutralizing antibody; neutralizing monoclonal antibodies; Non-Insulin-Dependent Diabetes Mellitus; novel therapeutics; Operative Surgical Procedures; patient population; Patients; pegvisomant; Phase; Pituitary Gland; Pituitary Neoplasms; Population Group; pre-clinical; Production; Pump; Research; research clinical testing; Respiration Disorders; Rodent Model; screening; Serum; side effect; skeletal; soft tissue; somatostatin analog; Somatotrophin increased; Somatotropin; Specificity; Technology; Testing; Therapeutic; Therapeutic antibodies; therapeutic candidate; Toxicity Tests; Transgenic Mice; Transgenic Organisms; Treatment Efficacy; tumor; Validation
