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

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 andquot podandquot IVR platform we will develop independent TDF and FTC andquot beadsandquot 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 Q Q 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 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 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 studies is none the less feasible Current competing strategies suffer from serious and potentially fatal scientific and regulatory flaws PUBLIC HEALTH RELEVANCE Dual protection is a high priority for the NIH the WHO and for leading NGOs such as the Gates Foundation Our strategy is based on piggy backing contraceptive and pre exposure strategies that are known to work We have manufactured generic NuvaRing r etonogestrel ethinyl estradiol and pod IVRs delivering Truvada r tenofovir disoproxil fumarate TDF emtricitabine FTC This Phase study will comprise manufacturing two products that when used simultaneously can provide both contraception and pre exposure prophylaxis against HIV