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HIV Glasgow: Generic Hepatitis C Drugs Purchased Online Produce High Cure Rates

Use of generic versions of direct-acting antivirals for hepatitis C resulted in very high cure rates for people who obtained the products through 3 buyers’ clubs, indicating that the generic products are effective, according to a set of poster presentations at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) last week. People who purchased generic drugs were cured at a cost of around US$700-$900 in Southeast Asia and Eastern Europe, Andrew Hill of St. Stephen’s AIDS Trust reported.

[Produced in collaboration with aidsmap.com]

Direct-acting antivirals (DAAs) used in interferon-free regimens typically cure 90% to 95% of hepatitis C infections, even in cases where people have advanced liver disease or previous experience of ineffective therapy.

But the price of treatment remains a major barrier to curing hepatitis C for millions of people worldwide, and where rationing of treatment, lack of health insurance, or lack of a national treatment program deny access to these drugs, people are turning to internet-based buyer’s clubs to obtain generic versions.

Generic versions of DAAs are manufactured in India under a voluntary license from Gilead Sciences, by other Indian companies that are not licensees, and in other countries such as Bangladesh where patents on the products do not exist and the lack of patent protection allows generic manufacturers to produce their own versions of the drugs. In many countries it is legal to import drugs for personal use by ordering them online. In other countries imports of generic drugs are restricted to those carried through customs by individuals in quantities sufficient for personal use.

A previous study by James Freeman in Australia showed very high cure rates when using generic versions of direct-acting antivirals, and also provided evidence that the purchased products contained the necessary levels of active drug.

The studies presented this week -- in which data supplied by patients and their physicians were analyzed by St. Stephen’s AIDS Trust in London -- measured virological responses; 2 studies identified the generic products used and 1 study was able to measure levels of active ingredients. The preliminary results of the 3 studies show cure rates comparable to those achieved with branded products.

FixHepC Buyer's Club

The FixHepC Buyer’s Club is an online service which directs people towards generic sources of hepatitis C drugs and arranges testing of the drugs to ensure that they contain the correct levels of active ingredients.

All drugs purchased by patients whose data were analyzed in this study had been tested for active ingredients. Patient data were gathered by Freeman and analyzed by St Stephen’s AIDS Trust. Patients were monitored remotely in many cases and were distributed across every continent. The data presented in Glasgow represent extended follow-up on 438 of the 448 patients previously described by Freeman.

The analysis showed that 59% of patients contributing data to this study had absent to moderate liver fibrosis (stage F0-F2), 11% had advanced fibrosis (stage F3) and 27% had cirrhosis (stage F4).

Patients used regimens including generic sofosbuvir (equivalent to brand-name Sovaldi) plus ribavirin, sofosbuvir plus daclatasvir (equivalent to Daklinza), and sofosbuvir/ledipasvir (equivalent to Harvoni).

Analysis of responses by HCV genotype showed that patients with genotype 3 were substantially less likely to achieve a sustained virological response compared to those with other genotypes. 80% of genotype 3 patients, predominantly treated with sofosbuvir/daclatasvir, achieved sustained virological response at 12 weeks post-treatment (SVR12) compared to 94% of genotype 1 patients and all patients with genotypes 2, 4, 5, and 6.

Overall, 90% of people who obtained drugs through the FixHepC Buyer’s Club and completed the 12-week post-treatment follow-up have achieved sustained virological response to date. The researchers also looked at rapid virological response (RVR), end-of-treatment response (EOT), and sustained response at week 4 post-treatment (SVR4).

Southeast Asia Buyer's Club

In Thailand a 12-week course of brand-name Sovaldi plus Daklinza costs around $10,000, and it is similarly priced in most other countries in the region. A buyer’s club based in Thailand directed people to online pharmacies in India to purchase generic versions of sofosbuvir and either daclatasvir or ledipasvir. Around 85% to 90% of the products supplied were manufactured by Cipla, one of the largest suppliers of quality-assured antiretroviral drugs for treatment of HIV. The buyer’s club collected patient data from physicians and the results were analyzed by St. Stephen’s AIDS Trust.

To date, 237 patients have begun treatment. SVR4 results are available for 33 and SVR12 results for 24 of them. Results to date show that 1 patient failed to achieve rapid virologic response on sofosbuvir/ribavirin, and one patient failed to achieve an end-of-treatment virological response on sofosbuvir/ledipasvir. IN addition, 2 patients taking sofosbuvir/ribavirin experienced virological rebound between weeks 4 and 12 post-treatment, resulting in a 85% SVR12 rate to date on this combination. All other patients who have reached 12-week post-treatment follow-up have achieved sustained virological response.

Russia and Eastern Europe Buyer's Club

Sofosbuvir is not available through the Russian hepatitis C treatment program and private treatment with the drug costs around $9,500 for a 12-week course. In order to obtain affordable treatment, people with hepatitis C are importing drugs from India, China, and Egypt with the support of the Gepatikta group on Facebook, at a cost of around $700-$900 per treatment course. Patient data for this study were assembled from private physicians and AIDS clinics in Russia, Belarus, Estonia, Israel, and Ukraine.

In the South-East Asia Buyer’s Club analysis the vast majority of DAAs were manufactured by Cipla, but in the Eastern European Buyer’s Club a wider range of manufacturers supplied products. Just over half of all drugs purchased were manufactured by the Indian company Hetero. The Egyptian manufacturer Natco supplied 14% of sofosbuvir, 16% of sofosbuvir/ledipasvir, and 7% of daclatasvir used by patients. Zydus supplied 11% of daclatasvir, and 16% of daclatasvir used by patients was formulated from active pharmaceutical ingredients supplied by Chinese manufacturers -- a process also followed by early participants in the FixHepC Buyer’s Club prior to the availability of generic formulations manufactured in India.

Just over half the patients in this cohort had HCV genotype 3 infection (56%), and 41% had genotype 1 infection. As in Southeast Asia, virological responses were poorer for genotype 3 patients. 82% of people with genotype 3 who had week 2 measurements of rapid virological response had viral load <25 IU/mL at this time, compared to 90% of those with genotype 1 and 88% with genotype 2.

A difficulty with making comparisons across these cohort is that measurements may be missing at various time points, people who fail to respond to treatment may cease, or people may be lost to follow-up as in any other study. Longer-term follow-up of these large groups of patients will be needed in order to produce more robust estimates of the proportions achieving SVR12, as well as any consistent differences by genotype.

10/29/16

Sources

A Hill, A Savage, G Jeffreys, et al. High sustained virological response rates using imported generic direct acting antiviral treatment for hepatitis C, imported into Australia, UK, Europe and North America. HIV Drug Therapy 2016. Glasgow, October 23-26, 2016. AbstractP256.

A Hill, J Dragunova, R Korologou-Linden, and S Golovin. Efficacy of generic direct acting antiviral treatment for hepatitis C, imported into Russia and Eastern Europe. HIV Drug Therapy 2016. Glasgow, October 23-26, 2016. Abstract P261.

R Korologou-Linden, A Hill, A Wardhana, and G Khwairakpam. Efficacy of generic direct acting antiviral treatment for hepatitis C, imported into Southeast Asia and China. HIV Drug Therapy 2016. Glasgow, October 23-26, 2016. Abstract 262.