Development of a bioabsorbable, subcutaneous, extended-release buprenorphine implant for opioid use disorder

Drug Delivery Company, Llc, The, Salisbury MD

Investigators

Abstract

Project Summary/Abstract The Drug Delivery Company (DDC) is developing a bio absorbable, extended-release buprenorphine implant. It is intended to help address the challenges posed by opioid use disorder (OUD) and the fentanyl overdose crisis. Currently, the longest-lasting formulation of buprenorphine (BUP) is a one-month long-acting injection (Sublocade ® and Brixadi ®). An extended-release buprenorphine (XR-BUP) implant, capable of releasing therapeutic levels of BUP for over 6 months, will improve medication compliance and provide a new treatment option for patients and healthcare providers. In collaboration with the National Institute on Drug Abuse (NIDA), DDC has been actively involved in developing a subcutaneous, bioabsorbable, extended-release 6-month naltrexone (NTX) implant since 2019. Building upon the success of the 6-month bioabsorbable naltrexone implant, known as the iSTEP-N®, DDC is now creating a 6-month bioabsorbable buprenorphine implant using the same technology. The iSTEP-N® utilizes a patented bioabsorbable drug delivery platform, which is protected by U.S. Patent No. 11,197,819. In pre-clinical studies, the iSTEP-N® implants demonstrated the release of therapeutic plasma levels of NTX for over 7 months in canines with a mean plasma concentration of 5.3 ng/ml, with detectable levels persisting for more than 8 months. The iSTEP-N® was well-tolerated, and no adverse events were reported. The FDA granted an Investigational New Drug (IND) approval without clinical hold [IND 152127] for the iSTEP-N®, allowing the company to commence a phase I clinical trial in healthy volunteers (Q2 of 2024). The development plan for the XR-BUP implant (iSTEP-B) will be to follow the roadmap that was used for the iSTEP-N® naltrexone implant. The chemical similarities between NTX and BUP allow for the loading of BUP into the iSTEP-N® drug delivery platform. This study is targeting the same plasma concentration for both the NTX and BUP implants, which is > 2-4 ng/ml throughout the entire 6-month duration of the implant. At this stage, there should only be minor adjustments made to the methodology used in developing the iSTEP-N® naltrexone implant. The development process for the bio absorbable, extended-release buprenorphine implant will follow the same pathway, including implant formulation, chemistry, manufacturing, and controls (CMC) analytics, non-GLP animal studies, GLP IND-enabling toxicology studies in rodents and canines, submission of the IND application to the FDA, and ultimately the completion of Phase I and Phase II Clinical trials. The effectiveness of a 6-month buprenorphine implant is expected to provide stability and support for OUD patients during those critical initial six months of recovery. Subsequently, with only two annual office visits required for a new XR-BUP implant, patients can focus on psychosocial therapy, recovery, and rebuilding their lives. An XR-BUP implant, releasing therapeutic buprenorphine for over 6 months, will enhance medication compliance and offers a fresh solution to opioid use disorder and the fentanyl overdose crisis.