The Bill & Melinda Gates Foundation and its funding partners in the Grand Challenges family of grant programs are inviting innovators to apply for grant opportunities. Here find one that may be of interest to LEAP investigators.
Owen A, Rannard S. Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy. Adv Drug Deliv Rev. 2016;103:144-156. doi:10.1016/j.addr.2016.02.003. PMID: 26916628; PMCID: PMC4935562.
Many terms have been utilised to describe the LA approach and standardisation would be beneficial. Ultimately, definitions will depend upon specific indications and routes of delivery. This review focuses upon the critical importance of potency in achieving the LA outcome for injectable formulations and explores established and emerging technologies that have been employed across indications.
A table outlining a target product profile for long-acting, extended-release ARVs
Dolgin E. Long-acting HIV Drugs Advanced to Overcome Adherence Challenge Nat Med. 2014 Apr 7;20(4):323-4. PMID: 24710366.
The results from a particular drug trial presented here last month at the annual Conference on Retroviruses and Opportunistic Infections (CROI) may not have seemed particularly noteworthy. It simply showed that two pills performed as well as another combination of medicines. But the antiretroviral agents tested in the trial were not your ordinary drugs.
Spreen WR, Margolis DA, & Pottage JC Jr. Long-acting injectable antiretrovirals for HIV treatment and prevention. Curr Opin HIV AIDS. 2013 Nov;8(6):565-71. PMID: 24100877; PMCID: PMC3815009.
Investigational long-acting injectable nanoformulations of rilpivirine and GSK1265744 are clinical-stage development candidates.
Rajoli RK, Back DJ, Rannard S, et al. Physiologically Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long-Acting Nanoformulations for HIV. Clin Pharmacokinet. 2015;54(6):639-650. doi:10.1007/s40262-014-0227-1. PMID: 25523214; PMCID: PMC4450126.
These data may help inform the target product profiles for LA antiretroviral reformulation strategies.
The Gates Foundation invests in areas that advance the development and delivery of new HIV prevention methods while improving the efficiency and effectiveness of existing prevention and treatment efforts.
Arya V, Au S, Belew Y, Miele P, Struble K. Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection. Curr Opin HIV AIDS. 2015 Jul;10(4):278-81. doi: 10.1097/COH.0000000000000163. PMID: 26049954.
Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately.