1-Year Sustained Release Naltrexone Implant for the prevention of relapse to opioid dependence

1 年持续释放纳曲酮植入剂，用于预防阿片类药物依赖复发

• 批准号: 9904461
• 负责人: FRANCIS JOSEPH MARTIN
• 金额: $ 257.27万
• 依托单位: DELPOR, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904461
• 关键词: Abdomen; Accidents; Automobile Driving; Biological Assay; Carboxylic Acids; Cessation of life; Chemistry; Chronic; Clinical; Clinical Trials; Consensus; Custom; Cyclic GMP; Databases; Development Plans; Device Designs; Devices; Diffusion; Dose; Drug Exposure; Drug Metabolic Detoxication; Economics; Ensure; FDA approved; Formulation; Future; Health Care Costs; Human; Implant; Injectable; Institutional Review Boards; Lead; Life Expectancy; Local Anesthetics; Maintenance; Maintenance Therapy; Medical; Methods; Naltrexone; Operative Surgical Procedures; Opiate Addiction; Overdose; Pain management; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Pilot Projects; Plants; Plasma; Positioning Attribute; Preclinical Testing; Probability; Procedures; Process; Product Labeling; Program Development; Prophylactic treatment; Rattus; Relapse; Reporting; Risk; Risk Assessment; Risperidone; Safety; Site; Sterilization; System; Tablets; Technology; Testing; Therapeutic; Titanium; United States National Academy of Sciences; Validation; alternative treatment; analytical method; animal data; base; clinical development; cost; design; disorder later incidence prevention; expedited review; human subject; improved outcome; manufacturing process; medication compliance; medication-assisted treatment; meetings; opioid epidemic; opioid misuse; opioid mortality; opioid use disorder; pill; pre-clinical; programs; prophylactic; response; safety study; subcutaneous; success; tool; usability

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.

阿片类药物流行病造成的人员和经济损失是惊人的。阿片类药物使用障碍（OUD）是公认的