Rosalyn, Kamaal, and Mohd Rashid Bin Hashim: activists and community leaders living with hepatitis C, at the Hospital Selayang, Batu caves, Selangor, Malaysia.
› Hepatitis C causes chronic liver disease, including
inflammation, cirrhosis, and hepatocellular carcinoma; an estimated 130-150 million people are chronically infected with HCV worldwide. This blood-borne virus is most commonly spread through unsafe injection practices, inadequate sterilization of medical equipment, and insufficient screening of blood products. HCV can also be transmitted sexually and from an infected mother to her baby, although this is less common. The virus exists with six major genotypes (GTs), but prevalence varies by region with GT1 most prevalent in high-income countries and GT3 in low- and middleincome countries (LMICs). In the last few years, direct acting antivirals (DAAs) have revolutionized the therapeutic landscape. These well-tolerated oral treatments have a cure rate of 95% or more and are taken once daily for 12 weeks, replacing the less effective regimen of weekly pegylated interferon injections, frequently administered with twice-daily oral ribavirin for up to 48 weeks, a therapy associated with unpleasant side effects. R&D efforts have focused principally on registering a product for the lucrative market in high-income countries, with little data available on efficacy in populations carrying the genotypes that are predominant in LMICs. The price of drugs is a major barrier to treatment access, with sofosvubir treatment costing $84,000 in the US, for example, and $94,000 when combined with lepidasvir.
A drug development strategy based on a public health approach
DND i aims to meet the specific needs of patients in LMICs by developing a short-course, affordable, highly efficacious, safe, and all-oral pan-genotypic regimen that will enable countries to implement a “public health approach” to the epidemic. It aims to identify and treat not only those in immediate need of therapy but all those infected, in order to prevent the long-term morbidity and mortality associated with HCV, and to reduce further transmission of the virus. This approach will build on the lessons learned from efforts to scale up HIV/AIDS treatment in resource-limited settings, and includes simplified models of care that allow for decentralization to the primary healthcare level, task-shif ting of clinical and nonclinical ser vices, and reduced dependence on genotyping and other expensive and sophisticated laboratory monitoring.
In April 2016, in partnership with the governments of Malaysia and Thailand, DNDi and the Egyptian generic drug manufacturer Pharco Pharmaceuticals announced an agreement to test an affordable HCV regimen. Phase III clinical studies will evaluate sofosbuvir plus the drug candidate ravidasvir. The efficacy, safety, and pharmacokinetics of the sofosbuvir and ravidasvir combination will be evaluated in approximately 1,000 patients with various levels of liver fibrosis, different genotypes, and with/without HIV co-infection. The company has also agreed to supply the sofosbuvir plus ravidasvir combination at a price of less than $300 per treatment course, both for and after the studies, if they are successful.
48 › DNDi Annual Report 2015