Research Project
10023928
The human and economic toll of the opioid epidemic is staggering. Opioid Use Disorder (OUD) is recognized as a chronic condition and Medication Assisted Treatment (MAT) is now considered first-line and an essential component of long-term treatment. FDA-approved drugs to treat OUD, including naltrexone, are effective and save lives. Long-term retention on medications is associated with improved outcomes. These are some of the conclusions of a recent National Academy of Sciences consensus report. In 2017 over 11 million people misused opioids, and over 2 million people reported having OUD. Drug overdose is the leading cause of accidental death in the US, and opioid overdose deaths drove down the US life expectancy over the last 3 years. The annual cost of the opioid crisis was estimated at $115 billion in 2017. MAT is one of the major pillars of the federal response to the opioid epidemic in the US. Naltrexone is one of the 3 medications commonly used to treat OUD, available as a once daily pill, or as a once-monthly injectable. Existing formulations have a short duration and a poor PK profile, resulting in poor medication adherence, with retention as low as 10% after 4 months. The lack of longer acting prophylactic pharmacologic options for OUD patients during maintenance therapy is an unmet medical need. Delpor is in a unique position to contribute, and quickly. The proposed product is a titanium implant loaded with a formulation of naltrexone and a naturally occurring carboxylic acid. The device is implanted subcutaneously in the abdomen via a custom implanter tool, with local anesthetic during a simple 10-minute in-office procedure. The technology is based on a unique formulation that keeps the pH within the reservoir low, and in doing so, promotes passive diffusion of naltrexone. The benefits of the product include: a) complete medication adherence for 1 year after one administration b) fewer relapses c) smooth PK profile ensuring complete prophylaxis without sub-therapeutic plasma troughs, d) full reversibility in case pain treatment is needed (accident, surgery), and e) same efficacy with less drug exposure. The technology has been validated clinically with another drug (risperidone), and tested preclinically with naltrexone. A preferred naltrexone formulation has been selected; preliminary animal data indicate zero order drug release without decline, and we predict that a 1-year system is achievable in human subjects with 2-3 devices. The UG3 phase of this application includes finalizing the Chemistry Manufacturing and Controls, producing IND supplies, conducting an IND enabling safety study, and submitting the IND. The UG3 transition milestone is the acceptance of the IND. The UH3 phase will complete the development program required for an NDA submission. The program will follow the 505(b)(2) regulatory path offering expedited review, and utilize studies already completed for Delpor?s lead program. The development plan has low technical risk, maximizing the probability of approval. The proposed project will result in an NDA submission for a 1-year naltrexone implant within 5 years, expected to reduce relapses, increase treatment success, and reduce healthcare costs.
