Preclinical development of a multipurpose intravaginal ring for the prevention of HIV and unintended pregnancy

Auritec Pharmaceuticals, Inc., Santa Monica CA

Investigators

Abstract

? DESCRIPTION (provided by applicant): The broad, long-term goal of this research program is to develop a dual protection intravaginal product that will provide contraception and pre-exposure HIV prophylaxis to women in the developing world. Dual protection is a high priority for the NIH, the WHO and for leading NGOs such as the Gates Foundation. NuvaRing(r) is the only intravaginal ring (IVR) approved for contraception. Truvada(r) [tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)] is the only drug approved for pre-exposure prophylaxis. Our strategy is based on delivering the drugs of the NuvaRing(r) in conjunction with the drugs of Truvada(r). In an adaptation of our pod IVR platform we will develop independent TDF and FTC beads that can be attached to an IVR. Simultaneously we will develop a generic version of the NuvaRing(r) that will be approvable through the ANDA mechanism. Through correspondence with the FDA we have determined the Target Product Profile (TPP) including qualitative and quantitative (Q1Q2) requirements for generic NuvaRing(r)s. We have determined the in vitro release methods and specifications and have manufactured batches of pilot generic NuvaRing(r)s. We have developed pod IVRs delivering TDF-FTC and have demonstrated safety, pharmacokinetics, and efficacy in sheep and primate models. The specific aims of this Phase 1 project will be to select the batch of generic NuvaRing(r)s that match the predicate release, to manufacture a pilot batch of the TDF-FTC pods, and to carry out a pilot safety-PK study to demonstrate feasibility in sheep. In Phase 2 and subsequent work we will confirm bioequivalence of the generic ring to the NuvaRing(r) leading to ANDA approval, and confirm bioequivalence of the contraceptive rings to the rings plus pods. Approval of the pods, although requiring large Phase 3 studies, is none the less feasible. Current competing strategies suffer from serious and potentially fatal scientific and regulatory flaws.