Tuesday, September 26, 2023
9/26/2023
Abstract/Summary This application requests a supplement to parent cooperative agreement UH3DA048387 and is in response to PA-20-272 Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional). The opioid crisis continues despite the availability of FDA-approved medications for treating opioid use disorder (methadone, buprenorphine, and naltrexone) and opioid overdose (naloxone). While these medications are effective in many patients, each has pharmacological properties that limit their clinical utility. Methocinnamox (MCAM) is a novel opioid receptor antagonist with pharmacological properties that could make it especially useful for treating opioid use disorder (i.e., preventing relapse) and overdose. A single dose of MCAM blocks the abuse-related and toxic effects of opioids for weeks in rats and nonhuman primates. MCAM initiatives currently underway at various contract research organizations (CROs) and supported by UH3DA048387 include the following: 1) good laboratory practice (GLP) in vivo (rats and dogs) and in vitro toxicology and safety pharmacology studies; 2) chemistry, manufacturing, and controls (CMC); 3) synthesis of non-GMP MCAM maleate to support the completion of IND-enabling nonclinical studies; 4) stability studies; and 5) development of a clinical plan. A pre-IND meeting with the FDA will occur in Summer 2023. An IND application will be submitted with the goal of conducting first-in-human studies in 2024. One US patent for MCAM was issued and three more are under review. The cost of the IND-enabling studies as well as the cost of preparing and submitting an IND application to the FDA have increased significantly and are much greater than budgeted in the original application. Due to unanticipated increases in the cost of studies with CROs that are required for the IND application, there are not sufficient funds in the current award to complete all of the necessary IND-enabling studies. This supplement requests additional funding to complete synthesis of non-GMP MCAM maleate at Veranova that will be used to complete the nonclinical toxicology and safety pharmacology studies at Charles River Laboratories. This program has the potential to significantly impact public health. MCAM has an exceptionally long duration of action, high oral bioavailability, can be synthesized economically at scale, and does not have any known adverse effects over a 3000-fold dose range – it has the potential to save lives.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
