The LONGEVITY project is designed to implement preclinical and clinical long-acting injectable product development for long-acting formulations for malaria and tuberculosis prevention, and a single-injection cure for hepatitis C by taking pre-existing oral medicines and repurposing them as injectable formulations administered far less frequently, and thereby reducing the effect that unsustainable oral regimens have on patients.
The University of Liverpool received funding from Unitaid to implement LONGEVITY
The project also involves critical partners in Johns Hopkins University, the University of Nebraska Medical Center, the Clinton Health Access Initiative, Treatment Action Group, Medicines Patent Pool and Tandem Nano Ltd.
Approximately 90% of malaria infections and deaths, 95% of tuberculosis infections and deaths, and 75% of people living with hepatitis C live in low and middle-income countries with a combined burden estimated at 300 million people with more than two million deaths per year in these regions. One of the critical issues with treating and preventing these diseases is adherence to daily medication with stigma, pill burden and delivery modes all contributing to individual and global mortality and emerging resistance.
Long-acting injectable medicines have already shown great promise for HIV therapy and prevention and have demonstrated impact in several other applications such as contraception and schizophrenia. This sets a precedent for the wide-ranging and currently untapped impact achievable across malaria prophylaxis, tuberculosis prevention and hepatitis C virus cure.
Several technologies exist for long acting drug delivery, each presenting different development, financial, clinical and logistical challenges and opportunities. Examples include injectables, implants and microarray patches currently at different stages of development. Implants are highly successful for potent drugs, but for most standard-of-care infectious disease therapies, the required concentrations are too high. Microneedle patches have shown early promise but may benefit from delivery of the formulations that ultimately control drug release.
The project uses Solid Drug Nanoparticle (SDN) technology that was the basis for the recent University of Liverpool spin-out, Tandem Nano Ltd. These new formulations can be dispersed for administration as long acting injections.
We will adopt technology that facilitates effective exposure to a drug for a period between one and four months. This new innovation offers potential for rapid development at low cost and with optimal product performance. Our approach will quickly develop cost effective options to deliver high doses of active pharmaceutical ingredients.
This project will truly expand global knowledge in long acting injectable development, regulation of this technology and its administration in healthcare provision.
LONGEVITY will impact malaria, tuberculosis and hepatitis C therapies in different ways:
Malaria is a huge burden in the poorest nations, disproportionately affecting children under five and those residing in rural areas. Approximately 92% of malaria cases and 93% of malaria deaths are within lower and middle-income countries. In 2017 children under five accounted for 61% of malaria deaths worldwide. These statistics can be reduced by tackling the issue of non-adherence and control of the disease. An anti-malarial long acting injectible prophylactic will address the lack of adherence to oral medicines while adding a key tool to support World Health Organisation control strategies. A long acting injectable chemoprophylactic will allow transmission control and aid future strategies to eliminate the disease.
Long oral regimens and poor patient acceptability contribute to ineffective and underutilized prevention therapies. Effective short courses exist but are costly and require daily or weekly intake resulting in less than 50% completion rate despite the potential for cure. There is also a significant issue with stigma in lower and middle-income communities resulting in an evident barrier in seeking treatment. Long acting injectable formulations will contribute massively to patient acceptability and completion rates of therapy by reducing the complexity of treatment. An administration of between one and two injections will replace a regimen of anywhere between one and 36 months and sometimes hundreds of doses of oral medication.
Approximately 75% of people living with hepatitis C reside in lower and middle-income communities with the majority of these communities having limited access to life-saving medication. It is estimated that oral drugs at the point of diagnosis provide a 98% cure rate. If this was replaced with a long acting injectable therapy we can provide much better accessibility to a curative treatment to those most affected by hepatitis C, contributing massively to the target set by The World Health Organisation for global elimination of this virus by 2030.
Our project aims to develop revolutionary long acting medicines for infectious diseases that have a major burden across low and middle-income countries. Although drugs exist for malaria and TB prevention and HCV therapy, they rely on individuals taking medication daily. Chronic oral dosing is extremely difficult to maintain over long periods leading to non-adherence that can negatively impact efficacy and exacerbate emergence of antimicrobial resistance.Andrew Owen, Co-coordinator of the LONGEVITY project
A Liverpool led research initiative has been awarded more than £2.2 million ($2.8 million) in funding from Unitaid for AGILE, a project to rapidly identify drugs to help treat and prevent COVID-19. The funding is part of the special investment approved by Unitaid’s Executive Board to bolster the COVID-19 response.