28 July is World Hepatitis Day, last year the Centre of Excellence for Long-acting Therapeutics (CELT) updated you with big news we presented at the Conference for Retroviruses and Opportunistic Infections (CROI) and this year we took even more.
What is World Hepatitis Day?
World Hepatitis Day is an awareness day designated by the World Health Organization (WHO). The purpose is to encourage more efforts locally and internationally in the response to hepatitis infections and impacts. WHO are aiming for global elimination of hepatitis by 2030 and will only achieve this by addressing the gap in low hepatitis testing and treatment coverage.
Viral hepatitis is caused by bloodborne viruses that can cause catastrophic inflammation of patients’ livers. Both hepatitis B and hepatitis C virus can lead to cirrhosis or liver cancer, which can be fatal. This makes hepatitis a life-threatening disease.
Summits and workshops bringing together researchers to collaborate on hepatitis B virus happen regularly, such as the Long-acting hepatitis B virus workshop we and our partners organised in March. Alongside hepatitis B, according to the WHO, around 50 million people are estimated to be living with chronic hepatitis C virus globally as well. However, the disproportionate majority of cases are in low- and middle- income countries (LMICs). 12 million patients are in the WHO Eastern Mediterranean Region alone.
The World Hepatitis Alliance announced that the theme for this year is ‘Let’s Break it Down: get the facts, take action’. The hope is that World Hepatitis Day this year can be used to unite the global community in demanding action from decision-makers. There is a lot of work being done globally in the hepatitis effort, but the numbers are going the wrong way and deaths are still going up each year. But why? We have fast and accurate tests, effective and affordable treatments and vaccines. It is believed that a large contributing factor is still stigma preventing people testing and accessing treatment and providers require additional education on the available products.
What is CELT’s hepatitis work?
Co-directed by Professor Andrew Owen and Professor Steve Rannard, CELT head an international consortium and partner organisations in a project called LONGEVITY, which is funded by global health agency Unitaid. Together we span the whole journey from conception to clinical trials for long-acting versions of existing drugs used in the treatment or prevention of hepatitis C virus, malaria and tuberculosis. The priority of any medication to come from LONGEVITY will be for patients in LMICs where these diseases are most prevalent and prove the most devastating.
What LONGEVITY hepatitis C virus findings did we present at CROI in 2025?
For World Hepatitis Day last year, we wrote a blog about a long-acting hepatitis C virus treatment breakthrough that we presented at CROI. This highlighted that LONGEVITY had preclinical proof-of-concept of a long-acting liquid injectable that would treat hepatitis C virus with one dose. This would eradicate the need to take three pills every day at very specific time intervals for 8-12 weeks.
This year, CELT’s Dr Usman Arshad presented similar findings that were different in one key area, we have preclinical proof-of-concept of an innovative long-acting solid injectable that could also treat hepatitis C virus with a single injection. Glecaprevir and pibrentasvir both showed sustained therapeutic concentrations in our in vivo studies.
The solid injectable yielded comparable drug release characteristics to the liquid injectable discussed last year. This means we could create different delivery format options of solid or liquid, and the data look promising. Like the liquid option, the solid injectable was well tolerated.
Concentrations were confidently sustained for 8 weeks in these studies, which matches the standard oral treatment regimen for hepatitis C virus. To simplify treatment further, we also saw rapid attainment of drug concentration, obviating the need for clinicians to lead patients into the treatment with oral pills first. A single injectable would be enough on its own to fully treat the patient, eliminating their hepatitis C virus infection.
What are the next stages for the solid long-acting injectable hepatitis C virus treatment?
Further investigation of the solid injectable is now required. This involves:
- Dose linearity and proportionality to understand the relationship between dose and human biological response
- Pharmacokinetic variability so we know that the same solid dose will be effective in all patients
- Modelling human doses and treatment durations so we know the clinical trials start with realistic dosing to avoid needing to repeat work.
These are all necessary steps to apply for approval to move to clinical trials. These are when the drug would be tested in humans for the first time.
Where are we up to with last year’s findings?
Last year our CROI presentation and World Hepatitis Day 2024 blog updated everyone on LONGEVITY’s exciting long-acting liquid injectable proof-of-concept. The work didn’t end with proof-of-concept and we’ve still been busy with the liquid injectable work.
Dr Henry Pertinez from our modelling team, has been working on predicting what concentrations may be achievable after administration to humans in clinical trials. The modelling estimates what the pharmacokinetics will look like after administration of different volumes of the liquid injectable, so we have an idea of how the body will absorb, metabolise, distribute and excrete the medication. We will use these results to explain to the regulators why we’re using these volumes in the human clinical trials.
The glecaprevir and pibrentasvir liquid long-acting injectable is planned to go to the first clinical trials in a human by mid-late 2026. To get us there, we’re currently writing the clinical protocol for the clinical trial with Professor David Thomas and the team from Johns Hopkins University School of Medicine, who will run the clinical trial providing the formulation is deemed acceptable to progress based upon non-clinical safety assessments.
What is the patient benefit of these findings?
Compared to standard oral daily pill regimens, a long-acting therapeutic option for hepatitis C virus could address challenges we see in LMIC patients, such as adherence issues. When pills aren’t taken on time, even by a small margin, it causes changes in the medication’s concentration in the body. Clinicians who came to speak to Dr Arshad during the poster presentation all mentioned dips in concentrations when their patients miss or even just mis-time a dose for any reason. They also discussed adherence difficulties connected to the stigma associated with requiring regular medication. All the clinicians gathered around Dr Arshad were excited for the implications of this research.
We want to provide a long-acting option for hepatitis C virus patients in LMICs, as options provide them an element of control and allow them to find the medication that best fits their lifestyle. We want to raise awareness of LONGEVITY’s long-acting treatment of hepatitis C virus, to help reduce the burden of oral treatments. We want to find a solution that aligns with the lifestyles of those experiencing the most devastating impacts of the disease. We want to be part of its eradication.
#WorldHepatitisDay
The LONGEVITY project aims to simplify hepatitis C virus, malaria and tuberculosis treatment and preventative treatment to reduce the drug burden and the number of patients requiring complex therapies for active disease.
Find out more about the LONGEVITY project
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
