An affordable cure to leave no one behind

First hepatitis C drug to be developed through South-South collaboration

Hepatitis C is one of very few diseases that could be eliminated globally with tools that exist today, provided there is political will to do so. The World Health Organization (WHO) has set a goal to eliminate viral hepatitis as a major public health threat by 2030, but only about one in five people living with hepatitis C today are aware that they are infected, and only 13% have had access to treatment. Roughly as many people are newly infected each year as receive treatment.

Although new safe and highly efficacious direct-acting antivirals (DAAs) have been available since 2013, access to affordable hepatitis C treatment remains extremely limited in many low- and middle-income countries. Securing widespread access to affordable combinations of DAAs that are optimised for public health is a critical step towards reversing this epidemic. 

In 2016, DNDi signed agreements with US biopharmaceutical company Presidio Pharmaceuticals, developer of the DAA drug candidate ravidasvir, and its licensing partner, the Egyptian generic manufacturer Pharco Pharmaceuticals, to enable testing of a new combination treatment using ravidasvir and sofosbuvir.

That same year, DNDi launched a Phase II/III study in Malaysia and Thailand to assess the efficacy, safety, tolerability, pharmacokinetics, and acceptability of 12- and 24-week ravidasvir + sofosbuvir regimens. The trial was co-sponsored by the Malaysian and Thai Ministries of Health and co-financed by the Médecins Sans Frontières (Doctors Without Borders, or MSF) Transformational Investment Capacity (TIC) initiative.

Final results of the first stage of the study published in The Lancet Gastroenterology & Hepatology in April 2021 showed that 12 weeks after the end of treatment, 97% of participants were cured. Cure rates were very high even for the hardest-to-treat patients. Importantly, patients combining several risk factors were cured, and no unexpected safety signals were detected.

In June 2021, the National Pharmaceutical Regulatory Agency (NPRA) of Malaysia granted a conditional registration for ravidasvir. In 2022, ravidasvir was officially launched in Malaysia, with the first patient treated with the combination of ravidasvir + sofosbuvir. Ravidasvir was included in the National Essential Medicines List (NEML), Ministry of Health Medicines Formulary (MOHMF), and WHO’s Essential Medicines List in 2023, and was recommended as one of the alternative treatments for HIV/HCV co-infected patients in the Malaysian Consensus Guidelines on Antiretroviral Therapy 2022.

DNDi and FIND have also partnered on a project in collaboration with the Ministry of Health in Malaysia to generate evidence to support policy change and scale-up of hepatitis C diagnosis and treatment. During the period 2021-2022, DNDi contributed as a supporting partner for a study on HCV self-testing, one of the first studies in the world to assess the impact of home-based HCV self-testing on the uptake of HCV antibody testing.

STORM-C-1: Sustained virological response at 12 weeks post-treatment, overall and in key subgroups – Full analysis set
STORM-C-1: Sustained virological response at 12 weeks post-treatment, overall and in key subgroups – Full analysis set
STORM-C-1: Sustained virological response at 12 weeks post-treatment, overall and per genotype – Full analysis set
STORM-C-1: Sustained virological response at 12 weeks post-treatment, overall and per genotype – Full analysis set

Impact

‘I had to wait and wait for years, but was eventually offered the ravidasvir + sofosbuvir combination treatment. I took the treatment for 3 months and my illness is no longer there.’

Huang Siang Ping, Farmer

‘The development of this new drug is the result of a partnership between public and private actors sharing the same public health objective from the very start: the development of an affordable medicine.’

Dr Bernard Pécoul, Founder, DNDi  

Project updates

2022

Following regulatory approval in Malaysia and Egypt in 2021, DNDi worked with partners ELEA, Grupo Insud, and Fundación Mundo Sano to submit the dossier for the registration of ravidasvir in Argentina in 2022. A decision is expected in 2023. Discussions related to submission in Brazil and Thailand are ongoing. DNDi also provided technical support to the Malaysia Ministry of Health-led EASE study – comparing the safety and efficacy of 8 versus 12 weeks of treatment with ravidasvir in non-cirrhotic patients – with recruitment expected to be completed in 2023.

The Hepatitis C Partnership for Control and Treatment (Hep C PACT) continued its work to advocate for the roll-out of all-oral cures, scale up community-based testing, and address domestic financing challenges and access barriers. DNDi, the Hepatitis Fund (End Hep 2030), and InTent hosted a side event on HCV financing, An SDG target we can reach: Financing viral hepatitis elimination, during the World Economic Forum in Davos, Switzerland in May 2022.

DNDi continued several access initiatives in Hep C PACT focus countries and regions. In Malaysia, seven workshops reaching 450 healthcare workers were held to support the decentralization of HCV management and discuss strategies to overcome barriers to scale-up of HCV services. In Bangladesh, DNDi supported national-level discussions on the design of innovative HCV screening and diagnosis strategies. In Cambodia, DNDi commissioned KOIS Caring Finance to conduct an economic analysis to assess the impact of implementing a national elimination programme for HCV in Cambodia, and supported a national workshop to discuss options for financing HCV diagnosis and treatment. In Latin America, DNDi facilitated a civil society organization workshop to plan an HCV treatment advocacy strategy. In Thailand, an HCV stakeholder meeting was held in January 2022, leading to key partners issuing a Joint Collaboration Statement on access to HCV treatment in June 2022.

2021

Final results of the first stage of the study published in The Lancet Gastroenterology & Hepatology in April 2021 showed that 12 weeks after the end of treatment, 97% of participants were cured. Cure rates were very high even for the hardest-to-treat patients. Second-stage results confirming the strong first-stage results will be published in early 2022. A clinical trial comparing 8-week versus 12-week courses of sofosbuvir-ravidasvir for the treatment of chronic hepatitis C, led by the Ministry of Health in Malaysia, is currently ongoing. 

In June 2021, the National Pharmaceutical Regulatory Agency (NPRA) of Malaysia granted conditional registration for ravidasvir as part of a combination treatment with sofosbuvir. DNDi and partners are now submitting the registration dossier in several countries in South-East Asia and Latin America to reach even more neglected hepatitis C patients. 

In July 2021, building on the success of the ravidasvir-sofosbuvir project, DNDi launched Hepatitis C Partnership for Control and Treatment (Hepatitis C PACT) with partners Médecins Sans Frontières (MSF), FIND – the global alliance for diagnostics, and Treatment Action Group. The aim of Hepatitis C PACT is to roll out all-oral cures, scale up community-based testing to find the missing millions of undiagnosed people, and address domestic financing challenges and patent and access barriers.

2020

Despite the challenges presented by COVID-19, recruitment for the second stage of the trial was completed in September 2020, with a total of 302 patients enrolled (177 in Malaysia and 125 in Thailand). Preliminary results from follow-up visits confirm the efficacy and safety results seen in the earlier stage of the trial. 

DNDi and Pharmaniaga submitted ravidasvir for regulatory approval with Malaysia’s National Pharmaceutical Regulatory Agency in late 2020. Registration in other middle-income countries, will be explored in 2021, including in Argentina with Laboratorio ELEA PHOENIX. 

2019

With the aim of enrolling 300 patients infected with genotypes 1a, 1b, 2, 3, and 6 – both with and without cirrhosis – the second stage of the trial was launched in late 2018, with the first patients enrolled in Malaysia in January 2019 and in Thailand in May 2019.  

As of January 2020, 180 patients had been enrolled, of whom 46 were in Thailand and 134 in Malaysia.  

Plans to submit for the conditional registration of ravidasvir with the Malaysian National Pharmaceutical Regulatory Authority are underway. 

2018

Interim results published in April 2018 showed that 12 weeks after the end of treatment, 97% of the 301 patients enrolled were cured (95% CI: 94.4-98.6). Cure rates were very high, even for the hardest-to-treat patients. Importantly, patients combining several risk factors were cured, and no unexpected safety signals were detected.  

To further establish the pan-genotypic profile of ravidasvir, the second stage of the trial was launched in December 2018 in Malaysia and in Thailand in May 2019. Other trials are envisioned in other parts of the world for vulnerable patient groups, such as people who inject drugs.  

Registration of ravidasvir will be pursued in Malaysia and other middle-income countries, including in Argentina, with DNDi’s pharmaceutical partners Pharmaniaga and Laboratorio ELEA PHOENIX, respectively.

2017

All 301 patients in DNDi’s Phase II/III trial combining ravidasvir and sofosbuvir in Malaysia and Thailand have completed treatment. Top-line results are being analysed and will be published in April 2018. 

DNDi  signed a technology transfer agreement with Pharco Pharmaceuticals (Egypt) and Pharmaniaga in late 2017.

2016

At the end of 2016, six study sites in Malaysia had recruited 164 patients (out of a target of 300) and four sites in Thailand had been initiated, with the full cooperation of the Ministries of Health in these countries.

Additional information