Almost a decade after they were first proven to be safe and highly effective, game-changing medicines to cure hepatitis C are finally becoming more widely available in South Africa. But not all the regulatory and other challenges behind the delay have yet been overcome and, as a result, access remains relatively limited for now.
The hepatitis C virus is a bloodborne virus, which can be transmitted through exposure to unsterilised needles and medical equipment, unscreened blood transfusions, and--less commonly--through sexual activity or mother-to-child transmission.
Around 30 percent of people who contract hepatitis C clear the infection from their bodies without treatment, but the remaining 70 percent develop chronic infection requiring treatment. Left untreated, chronic hepatitis C infection can cause life-threatening liver disease and liver cancer.
The DAA revolution
Over the last decade, a new class of medicines called direct acting antivirals, or DAAs, has transformed hepatitis C treatment. A standard DAA treatment regimen typically requires the use of two medicines, often combined in a single pill, for 12 weeks and cures around 95% of people. The medicines used prior to DAAs, involved regular injections, could last 24 to 48 weeks, had many more side effects, and were less effective at curing the infection.
In addition to being more tolerable and easier to take for individuals, the simple pill-based DAA regimens also allow for the more rapid scaling up of hepatitis C treatment in health systems. Such scaling-up can both curb onward transmission of hepatitis C and reduce the need for more costly future care of hepatitis C associated liver disease.
Yet, the promise offered by DAAs was initially obstructed by the sky-high price tags affixed to these medicines by the pharmaceutical companies that first brought them to market. Gilead, the company that lead the way with the first key DAAs, initially priced its products at over R1 million per treatment course. Those high prices became the subject of a high-profile United States Senate investigation that was critical of Gilead's pricing practices.
Activists and global health actors such as the World Health Organization and UNITAID pushed back against the excessive prices and, drawing from lessons and experience in securing access to affordable HIV medicines, eventually secured licensing and pricing deals that have allowed developing countries to procure DAAs from generic suppliers at a fraction of the prices initially charged by Gilead.
Generic companies whose DAAs have been preapproved by the World Health Organization for meeting safety, efficacy, and quality standards have agreed to market their pangenotypic DAA regimens at ceiling prices between R1 136 and R3 296 per treatment course. A pangenotypic regimen is a regimen that works for all hepatitis C strains and does not require genotype testing prior to treatment initiation.
Sofosbuvir/daclatasvir is the most affordable pangenotypic DAA regimen available globally. Generic suppliers with WHO preapproved versions of this product recently agreed to sell sofosbuvir/daclatasvir to eligible low-and-middle-income countries at R1 136 ($60) per treatment course. Although, due to regulatory challenges (of which more below), generic versions of this treatment combination are unlikely to be registered in South Africa.
WHO prequalified generics are also available of another important pangenotypic regimen--sofosbuvir/velpatasvir--to eligible developing countries at a price of R3 296 ($174) per treatment course.
What DAAs are available in South Africa?
After years long regulatory delays, on which Spotlight previously reported in-depth here and here, two DAA regimens were finally registered in South Africa last year.
During 2022, the South African Health Products Regulatory Authority (SAHPRA) registered Gilead's sofosbuvir/velpatasvir (Epclusa) and sofosbuvir/ledipasvir (Harvoni) regimens. While Epclusa is pangenotypic, Harvoni is only effective in patients with certain hepatitis C genotypes.
Gilead launched its Epclusa and Harvoni products in South Africa in November 2022, at the Single Exit Prices (the prices charged at private pharmacies and health facilities) of R28 664 and R23 409, respectively, for a treatment course. While Gilead has offered a lower price to the public sector for its pangenotypic Epclusa regimen, this price is not yet in the public domain.
"The fact that DAAs have been registered is a step forward, the next challenge is cost and access," Professor Mark Sonderup, hepatologist at UCT and Groote Schuur Hospital in Cape Town, told Spotlight.
Importantly, the registration of Gilead's originator version of Epclusa allows for generic companies to seek registration in the country. Generic competition is expected to usher in far lower prices than those offered by Gilead.
However, the registration of generic versions of sofosbuvir/daclatasvir (the most affordable DAA product) is unlikely in South Africa. This is because the originator version of daclatasvir has not been registered in the country. Generics are typically registered in reference to an already registered originator product.
SAHPRA recently confirmed to Spotlight that, given the absence of a registered originator, generic daclatasvir (as a stand-alone product or in combination with sofosbuvir) would need to be registered as a new chemical entity. Spotlight has previously written in-depth about why it is unlikely that a generic company will pursue this unusual path (see here and here.)
Working with what is available in the country, the National Department of Health (NDoH) is now considering the inclusion of sofosbuvir/velpatasvir on South Africa's Essential Medicines List (EML) for treatment of hepatitis C.
How were DAAs used in the country before registration?
While DAAs were only registered in South Africa last year, they have been available for several years to patients seeking care from Groote Schuur Hospital and the University of Cape Town's Liver Clinic. This is because Sonderup, along with Wendy Spearman, and colleagues successfully sought Section 21 authorisations from SAHPRA to use unregistered DAAs for their patients, as well as hospital and provincial-level agreement to support use of the medicines.
Section 21 authorisations have also been used to access generic DAAs for use in NGO-led pilot and subsequent treatment programmes focused on people who inject drugs and people in correctional facilities.
People who inject drugs that don't have access to needle and syringe exchange services are particularly vulnerable to hepatitis C infection as the virus can be spread through needle sharing.
Andrew Scheibe, technical advisor at TB HIV Care and researcher at the University of Pretoria's Department of Family Medicine, told Spotlight that several NGO-run sites providing harm reduction services to people who inject drugs now also provide HCV testing and treatment with support from the Global Fund, but that access remains largely limited to a few major metropolitan areas.
In addition to community-level sites providing DAAs to people who inject drugs, the provision of HCV testing and treatment services at correctional facilities is being piloted by TB HIV Care. While the pilot programme has initially focused on inmates in the Goodwood Correctional Centre, TB HIV Care is exploring options to expand the pilot programme to other prisons.
There is concern, however, that the registration of Gilead's originator products may drive up the costs of HCV treatment for NGO-led initiatives that have previously accessed generic DAAs through Section 21 approvals from SAHPRA. The expectation is that, now that there is a registered product in the country, these programmes will have to procure Gilead's product instead of importing cheaper, unregistered generics.
Scheibe also notes that, because NGOs must purchase medicines from the private sector, they will not have access to lower prices offered to the public sector unless an arrangement with government and Gilead can be made.
Adding DAAs to the essential medicines list
Now that DAAs are registered in South Africa, their inclusion on the Essential Medicines List (EML)--which outlines which medicines should be available within the public sector and at what level of care--can be considered. According to Khadija Jamaloodien, director of the Affordable Medicines Unit at the NDoH, this process has already begun.
"The NEMLC [ National Essential Medicines List Committee] is currently considering the DAA: sofosbuvir/velpatasvir (epclusa®). The review and costing analysis will be presented for consideration at the July NEMLC meeting for recommendations to be made," said Jamaloodien.
She added that "only sofosbuvir/velpatasvir was considered [for EML inclusion] as it covers all phenotypes and can be used in a 'fire and forget' manner, which alleviates the need for testing and confirming phenotypes."
The review process is currently considering the inclusion of DAAs "as part of the Tertiary and Quaternary Essential Medicines List, thus the use of these agents will need to be specialist initiated," said Jamaloodien.
Scheibe told Spotlight that limiting DAA accessibility to hospital levels "means it will be inaccessible broadly to the vast number of people who need it," but added "it first has to go on the Essential Medicines List at some point before we can start advocating for it elsewhere."
Pairing DAA provision with harm reduction services
Koketso Mokubane, a member of the South African Network of People Who Use Drugs, has firsthand experience of accessing a cure for hepatitis C. Mokubane told Spotlight that he connected with a trial study providing HCV testing and treatment services when seeking needle and syringe exchange services from Sediba Hope Medical Center in Pretoria, where he learnt that he had hepatitis C.
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"I did an introspection on myself, and I started to worry about my health," said Mokubane. He went on to start opioid substitution therapy to treat his drug dependence as well as DAAs to treat hepatitis C.
"Because I was at the right place at the right time I enrolled and I remember I was patient zero, I was the first patient in the [DAA] program", says Mokubane. "Now I'm living in my own place. I'm have my girlfriend...my life has taken a turn for the better."
Mokubane now advocates for greater community level access to harm reduction and health care services for people who use drugs. "I believe this [DAA] treatment needs to be accessed at facilities that are already providing comprehensive packages of harm reduction interventions...those places that are already a home for people who use drugs, whereby we are able to relate easily with the health professionals." He adds that people from the community should be hired to assist in educating and recruiting people who use drugs to access harm reduction and other healthcare services.
Accessing DAAs in the private sector
For private sector users, the registration of DAAs should broadly expand access to these medicines as they are now available around the country, and not only in locations where specialist physicians have secured Section 21 approvals from SAHPRA. As hepatitis C is not a prescribed minimum benefit (PMB) [a condition that private medical insurers are required to provide coverage for], the cost of DAAs through the private sector may be a barrier to access for some private sector users.
Private medical schemes may however follow the lead of Discovery Health and provide coverage for DAAs despite hepatitis C not being a PMB, given the cost-effectiveness of these treatments.
Dr Noluthando Nematswerani, Chief Clinical Officer at Discovery Health, told Spotlight "Discovery Health Medical Scheme currently provides cover for these medicines across all plan types".
"Discovery looked at the budget impact of funding the direct acting antivirals (DAAs) for hepatitis C. Prior to DAA's, hepatitis C was treated with pegylated interferons, which are a high cost, not curative and require long treatment duration. Due to the once-off treatment of DAA's, short duration (12 weeks) of treatment, curative intent in hepatitis C treatment and significantly lower treatment cost in South Africa, the decision was made to provide funding," says Nematswerani.
