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Development of Long-Acting Formulations of HIV Anti-Retrovirals


Background Effective treatment of HIV-infected individuals requires strict adherence to a multi-component regimen of antiretroviral agents that currently must be taken daily on a life-long basis. Non-compliance with recommended dosing regimens is a significant factor contributing to the incomplete suppression of HIV and to the development of drug resistance. The development of long-acting formulations that might significantly simplify the dosing requirements potentially could facilitate improvements in patient adherence. Long-acting formulations also would have utility as components of drug regimens provided to uninfected individuals for pre-exposure prophylaxis (PrEP) purposes. Some orally administered antiretrovirals readily penetrate and accumulate in rectal and female genital tract mucosa and achieve concentrations in those tissues higher than in plasma. Formulations based on antiretrovirals with these properties might have utility both as systemic and PrEP agents and thus are particularly attractive as formulation development candidates. Project Goals The goal of this SBIR contract solicitation is to support small businesses interested in developing novel formulations of antiretroviral drugs that can achieve clinically relevant systemic or tissue concentrations and maintain these levels for an extended period of time. Formulations that need only be administered once per month are of particular interest; however, formulations that extend the dosing interval to once a week or better still might be valuable additions to current or future PrEP and treatment strategies. Antiretroviral agents selected for formulation development should either be FDA-approved or in mid- to late-stage preclinical development (estimated time to clinical evaluation of 1-3 years). Offerors will be responsible for obtaining the parent antiretroviral compounds for their formulation efforts and for resolving any intellectual property issues that might arise regarding use of these compounds. Phase I Activities 1. Develop prototype formulations that address the goals of this solicitation. 2. Develop analytical assays that can be used to assess formulation purity and stability. 3. Assess the pharmacokinetic profile and safety of the formulations in an uninfected animal species. 4. Submit promising formulations to NIAID, if requested, for evaluation in either in vitro HIV-inhibition assays or small animal models of infection. Phase II Activities 1. Scale-up the formulations (activity need not be compliant with cGMP) for further preclinical studies. 2. Conduct additional pharmacology and toxicology evaluations of the formulations in uninfected animals. 3. Conduct bioequivalence studies in uninfected animals.
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