For World Hepatitis Day 2024 we highlight the exciting findings we presented at CROI
Posted on: 28 July 2024 by Rebecca Derrick in LONGEVITY Blog
28 July is World Hepatitis Day. Hepatitis C virus is one of the three diseases the LONGEVITY project is working to be part of the eradication effort for, so we wanted to update you on recent findings in our long-acting therapeutics research.
What is World Hepatitis Day?
The World Hepatitis Alliance use the 28 July to mark World Hepatitis Day, not just celebrate the progress so far but to raise awareness of the global burden of the disease and influence real change for those it impacts.
In April, the World Health Organization (WHO) highlighted that globally 3500 people daily die due to hepatitis, and 242,000 deaths were caused by hepatitis C virus (HCV) alone in 2022 (WHO). It is critical that researchers continue to tackle this disease.
HCV infection causes inflammation of patients’ livers. This inflammation can lead to liver cirrhosis and cancer which can result in death. The virus is present in every WHO global region, but is disproportionately prevalent in low- and middle- income countries (LMICs).
HCV is treatable, but often requires three pills a day for around 8 weeks and keeping up with such a strict medication regimen is leading to low adherence rates in the places most affected by it.
What is CELT’s hepatitis C work?
The Centre of Excellence for Long-acting Therapeutics (CELT) take existing or new drugs and create long-acting versions of them. One of our biggest projects is the LONGEVITY project, funded by global health agency Unitaid. LONGEVITY is a consortium led by CELT, but draws together expertise from several key partners with different expertise. The shared purpose of all the consortium members within LONGEVITY is to find long-acting therapeutic options for tuberculosis, malaria, and HCV. We can see that these diseases are all most prevalent in LMICs, despite being treatable, so our hope is that long-acting treatments will eliminate some of the reasons why patients can’t adhere to current drug regimens.
One of the additional benefits of a long-acting treatment for HCV is that if the disease requires 8 weeks of treatment to be cured in most cases, then a long-acting treatment that lasts 8 weeks within the body would mean that one dose would be enough to cure the infection. We’re working to take drugs we already know safely treat HCV and create long-acting versions of them so people can be cured upon diagnosis.
Who is Dr Usman Arshad?
Dr Arshad’s journey started with a Pharmacology undergraduate and a Masters in Drug Discovery. This included an internship at a major pharmaceutical company which sparked Usman’s interest in research and led to his application for a PhD at the University of Liverpool connected to Cancer Research UK.
The grant involved working with interdisciplinary teams to develop nanoparticle interventions for colorectal cancer, supervised by CELT’s co-Directors Prof. Andrew Owen and Prof. Steve Rannard, all culminating in a funded postdoctoral research associate position with the LONGEVITY grant after completing his PhD. Usman is a key member of the bioanalytical team working alongside Dr Paul Curley with techniques including liquid chromatography mass spectrometry (LCMS).
What hepatitis C development did Dr Arshad present at CROI 2024?
Usman was part of the HCV LAI development within LONGEVITY, which was a collective effort with contributions from various disciplines within the CELT team; chemists, modellers, and lab teams. CELT’s work in this space starts with a pharmacological assessment of compatibility of the drugs, before proceeding to feasibility studies by our chemistry team to create long-acting formulation options. These formulations then undergo extensive preclinical pharmacology testing in laboratory studies. The bioanalytical team process samples to measure drug concentrations, and the modellers then analyse and interpret the data. To present recent findings, Usman spent time collating all the data the group generated to share with the wider scientific audience at the Conference on Retroviruses and Opportunistic Infections (CROI) and showcase the HCV work from CELT. Usman's talk was titled 'Preclinical Pharmacokinetic Assessment of a Hepatitis C Virs Lon-acting Formulation".
The project involved the development and preclinical pharmacological assessment of a HCV long-acting therapy. These treatments have the potential to overcome challenges faced by currently licenced oral HCV antiviral drugs, including adherence, access, cost, lack of motivation and protection of healthcare privacy. In LMICs, sustained virological response rates in current treatments is considerably lower than what was seen in clinical trials, and it seems to be due to the above difficulties with patients discontinuing treatment, not the efficacy of the drugs.
At CELT we’re developing a therapy that will provide at least 8 weeks of sustained drug exposure from a single dose, rather than the 168 pills it currently takes. We believe that for nearly all patients, this would create a single-shot cure providing an alternative therapeutic option. This means that patients can receive the drug at diagnosis and potentially be cured as it will keep the drug levels above what is needed.
Dr Arshad presented pharmacokinetic data generated at CELT and showed that the long-acting injectable in a fixed dose combination resulted in longer half-life and improved drug exposure, providing preclinical proof of concept for the long-acting combination.
What are the next steps?
Adding to this exciting finding that the long-acting injectable should provide a single-shot cure for most patients, the toxicological assessments so far have also shown no adverse effects of the long-acting injectable.
Formal toxicology studies are now needed to show that the long-acting therapy is safe, before we can progress to clinical translation. In this instance clinical translation means scaling up drug manufacturing for bulk production of the medicine, so there is a validated process and enough of the formulation to run a clinical trial.
Who is responsible for the clinical trial phase?
As mentioned above, the LONGEVITY project is made up of several partner organisations who each specialise in a different part of the journey from conception to distribution in the LMICs most in need of the long-acting therapeutics that come from our work. This means that as CELT’s preclinical research reaches a conclusion, collaboration with another team within the consortium is needed to bring their expertise to bare for the next stages.
John’s Hopkins University School of Medicine (JHU), in Baltimore USA, is one of the LONGEVITY consortium members. The investigators from their team involved in LONGEVITY span from medicinal chemistry through to clinical trials and it’s the latter that will move to the next stages of the work.
The clinical translation of the drug will be overseen by Dr David Thomas and Dr Craig Hendrix and their teams at JHU, to examine the duration of exposure of the new drug formulation. The next step is to evaluate the medication in humans. This process begins with making sure it is safe and to confirm that the two individual drugs, are released into the blood in the desired amount and duration. If that process, also called a phase 1 trial. Ultimately, the aim is to translate the work to combat hepatitis C in LMICs where options are limited.
Why are the finding’s Dr Arshad presented important to patient care?
Patients around the world, especially in LMICs, don’t have direct access to a lot of the medications they need. If we can provide the option of a single-shot cure that can be administered at the time of diagnosis, a ‘test and cure’ approach to treatment, we believe we will reduce HCV around the world. A single-shot cure could eliminate adherence difficulties to difficult drug regimens, and significantly reduce costs while also addressing access issues in LMICs. Unfortunately, there is still a lot of stigma attached to taking regular tablets in many LMIC communities, so a single-shot cure would remove this additional difficulty.
A test and cure approach to hepatitis C virus will provide more options to patients, allowing them to decide how they access their treatment in the best way for them.
The LONGEVITY project aims to simplify and optimise delivery of hepatitis C virus drugs in the hope of making strides towards eliminating this enormous unmet healthcare need.
Find out more about the LONGEVITY project's HCV work
The LONGEVITY Project is funded by global health agency Unitaid
The project also involves critical partners and collaborators in the Clinton Health Access Initiative, Johns Hopkins University, Medicines Patent Pool, Tandem Nano Ltd., Treatment Action Group and the University of Nebraska Medical Center
