Phase II year
2017
(last award dollars: 2018)
Phase II Amount
$1,475,430
The prevalence of Type 2 diabetes is expected to reach 20%-30% by 2050, and according to the Centers for Disease Control and Prevention, as many as 1 in 3 U.S. adults could have diabetes by 2050. In the last 10 years, a new class of drugs, called incretin mimetics, has been used successfully for the treatment of the disease. Incretin mimetics (including exenatide) have a very short half-life requiring frequent subcutaneous self-injections. Such delivery can be invasive, painful, present safety issues, and impact the patientÂ’s attitude towards medication adherence. Maintaining peptide stability and enabling the sustained long-term delivery of exenatide are expected to improve compliance, convenience, safety, cost, and treatment success. The current long acting formulation of exenatide is for only 1 week and does not allow for medication removal if needed. The goal of the proposed program is to develop a small non-mechanical (passive) subcutaneous implant (reservoir) which will be able to deliver consistent, therapeutic levels of stable exenatide over a period of at least 3 months. The implant body is made of titanium and it is implanted subcutaneously in the upper arm or abdomen via a trocar, with local anesthetic during a simple 15-minute in-office procedure, and without the need for any surgical sutures. The implanted reservoir is fitted at one end with a nanopore membrane fabricated to contain pores with diameters that are approximately twofold larger than the hydrodynamic diameter of the selected drug molecule; such membrane architecture has been shown to result in zero-order release kinetics. The proposed delivery method will eliminate the need for daily or weekly self-injections. Benefits include medication adherence, patient convenience, improved safety and efficacy, and cost effective maintenance therapy. Furthermore, the system will allow healthcare providers to quickly remove the medication if needed, an important consideration, as this class of drugs has been associated with acute pancreatitis. The successful completion of Phase I has resulted in the development of a stable formulation of exenatide at body temperature, and has validated that the selected nanopore membrane is not subject to biofouling when exposed to in-vivo conditions and is robust enough to advance into preclinical studies, product development, and clinical testing. Our proposed work in Phase II will introduce and validate additional peptide analytics, optimize and validate the nanopore membrane manufacturing process, design and fabricate a clinical device and implanter tool, complete the preclinical proof-of-concept, and prepare a briefing package in order to conduct a pre-IND meeting with the FDA. The Company has already received feedback from the FDA on a similar implant for its lead molecule. Upon successful completion of the proposed study, Delpor will be ready to further advance the proposed product into the IND phase. Successful completion of the Phase II aims will also allow us to potentially extend the duration even further, and explore using the same technology for the delivery of other biologics (e.g., basal insulin, human growth hormone, octreotide, obesity peptides, etc).
Public Health Relevance Statement: PROJECT NARRATIVE According to the Centers for Disease Control and Prevention, as many as 1 in 3 U.S. adults could have diabetes by 2050, accounting for over 10% of total healthcare costs. The aging and overweight patient population, along with rising healthcare costs, have shifted the industry focus from acute care to cost effective chronic disease management. The proposed product will provide a safer, more efficacious, cost effective, and less invasive maintenance therapy for patients suffering from type 2 diabetes, and the validation of the proposed technology will create the potential for a safer, and more convenient delivery of biopharmaceuticals (proteins and peptides).
Project Terms: Abdomen; Accounting; Acute; acute pancreatitis; Adult; Aging; analog; Architecture; Attitude; basal insulin; Biological Assay; Biological Markers; Biological Products; biomaterial compatibility; Blood Glucose; Body Temperature; Caliber; Caring; Centers for Disease Control and Prevention (U.S.); Chronic Disease; Clinical; Clinical Trials; cost; cost effective; design; Development; Devices; Diabetes Mellitus; diabetes mellitus therapy; diabetic rat; Disease; Disease Management; disorder prevention; Drug Kinetics; Excision; exenatide; Feedback; Formulation; Freezing; glucagon-like peptide 1; Glucose; Glycosylated hemoglobin A; Goals; Half-Life; Health Care Costs; Health Personnel; Hormones; Hydration status; Implant; implantable device; improved; in vivo; Industry; Injection of therapeutic agent; Insulin; Kinetics; Lead; Liquid substance; Local Anesthetics; Maintenance; Maintenance Therapy; manufacturing process; Measures; medication compliance; meetings; Membrane; Methods; mimetics; Miniaturization; nanopore; Non-Insulin-Dependent Diabetes Mellitus; novel drug class; Obesity; Octreotide; Overweight; Pain; Pancreas; patient population; Patients; peptide drug; peptide L; Peptides; Pharmaceutical Preparations; Phase; Plasma; pre-clinical; preclinical study; Prevalence; Procedures; Process; product development; Production; programs; Proteins; Rattus; Reporting; research clinical testing; Resistance; Risk; Safety; Somatropin; subcutaneous; success; Surgical sutures; System; Technology; Testing; Therapeutic; Time; Titanium; tool; Toxicology; Treatment outcome; treatment response; trend; Trocars; Upper arm; Validation; Vendor; Withdrawal; Withholding Treatment; Work
