Auritec Pharmaceuticals has received a Phase II SBIR funding in the amount of $1,301,280 for assessing the clinical safety and pharmacokinetic studies of intravaginal rings (IVRs) releasing multiple antiretrovirals. The development of an effective microbicide IVR could save millions of lives per year and is therefore highly significant.

The goal of this project is to prevent HIV transmission. Using the drug delivery platform that we developed for the ganciclovir intraocular implant, Vitrasert®, we propose to develop an IVR releasing the antiretroviral agents tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and mararviroc (MVC). This drug combination has been chosen for potency, synergistic action, and the prevention of resistance. The rationale for the choice of TDF and FTC is very strong: these are the drugs in Truvada® and have demonstrated efficacy in clinical studies of HIV transmission. MVC has demonstrated protection against SHIV transmission in macaques. Funded in part by R21, R33, and SBIR grants from the NIAID, we have successfully adapted the Vitrasert® platform and safely delivered multiple antiretrovirals in multiple animal models.

The goal of this Phase II SBIR proposal is to carry out a 7-day open-label first-in-human safety and PK assessments of the following drug combinations - TDF, TDF-FTC and TDF-FTC-MVC. The IVRs will be worn by normal volunteers for 7 days. Safety will be determined by colposcopy and a novel ultrasound procedure which we pioneered, as well as cytokine measurements and assessments of the microbiome. Pharmacokinetics will be determined by measurement over time in local tissues and fluids, as well as in plasma. On completion of the 7-day study there will be a washout period and the data will be presented to the FDA. If there are no safety concerns after wearing the ring for 7 days, the study will be repeated over a 28-day period. Subsequent SBIR Phase III studies are planned in African populations.

The milestone of this proposal will be the successful completion of this clinical trial demonstrating safety and local delivery of the drug sufficient to merit further clinical trials in pursuit of FDA approval and clinical implementation. The successful completion of this work will be followed by studies and programs to manufacture these rings on a large scale and perform the clinical trials necessary for ultimate approval.