Generic versions of direct-acting antivirals purchased from
China and India by people unable to obtain treatment in their own countries
were just as effective and safe as the branded products, a study of 139
patients monitored by Australian doctor James Freeman has shown. The findings
were presented in a late-breaking research session at the International Liver
Congress in Barcelona on Saturday.
The study presented preliminary data on sustained virological
responses four weeks after the completion of treatment, labelled SVR4. The gold
standard measurement of cure in hepatitis C is the absence of detectable virus
12 weeks after completing treatment (SVR12), but SVR4 results tend to provide a
strong indication of SVR12 results, since the majority of cases of viral
relapse occur in the four weeks after completion of treatment.
The high cost of branded direct-acting antivirals has led to
rationing of treatment, slow drug approvals and refusal of insurance coverage
in many countries. People unable to obtain hepatitis C treatment through
existing health care have turned in desperation to the FixHepC
buyer’s club for help in obtaining generic versions of sofosbuvir,
sofosbuvir/ledipasvir and daclatasvir.
- compensated cirrhosis
The earlier stage of
cirrhosis, during which the liver is damaged but still able to perform most of
its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
Importation of medicines for personal use is permitted under
customs regulations in Australia and the United Kingdom, and many other
countries have regulations permitting the importation of small amounts of
medicines for personal use or their carriage through customs in personal
luggage. The FixHepC buyer’s club provided advice and information on how to do
this safely and legally, starting in Australia, but soon responding to
enquiries from people in Europe, North America, New Zealand and South East
Dr James Freeman, a doctor based in Hobart, Tasmania, started
to take an interest in how to treat patients safely with generic direct-acting
antivirals after a patient came to him and asked for advice on how to import
and use active pharmaceutical ingredients, obtained from Chinese manufacturers,
to treat hepatitis C. Dr Freeman arranged to have them tested to ensure that
they were indeed active drug, and to have the chemicals compounded into pills
in Australia. The FixHepC buyer’s club was born.
Product obtained from China and subsequently formulated into
pills was tested by nuclear magnetic resonance spectrometry, a technique used in
pharmaceutical manufacturing to measure the quantity of active pharmaceutical
ingredient in a pill. All products contained active drug in the expected
After generic products became available from manufacturers
in Bangladesh and India, the buyer’s club discouraged imports from China and
began arranging for individuals who wanted to obtain direct-acting antivirals
to buy products from reputable suppliers in India, in order to reduce risks in
the supply chain.
In January 2016, Dr Freeman began enrolling
patients who used the buyer’s club to obtain medication in an observational cohort
study, the Reviewing DAA Efficacy Managing Patient Treatment In Online
Neighbourhoods (REDEMPTION) study.
Treatment used in this study cost between US$1400 and $1600 for a course of
medication, compared to a cost of up to $84,000 for sofosbuvir (Sovaldi) and $94,500 for sofosbuvir/ledipasvir (Harvoni) in the United States. Prices of
generic products manufactured in India are likely to fall, possibly as low as
$200 per course of treatment, as production increases.
The findings presented at the International Liver Congress
are virologic response data four weeks after completion of treatment for the
first patients without decompensated cirrhosis who obtained generic products
with the support of the FixHepC buyer’s club and who were monitored through the
Australian gp2u.com.au telemedicine platform. Virological monitoring was
carried out by the patients’ own doctors.
Of the 448 patients enrolled to date, 48.4% had undergone
previous treatment for hepatitis C, 31% had cirrhosis and the average age was 54 years.
Genotypes 1 and 3 predominated (63.9% and 27.5% respectively). The most
commonly used combinations were sofosbuvir/ledipasvir (45.8%) and
sofosbuvir/daclatasvir (42.6%). A small minority used either sofosbuvir/ledipasvir
and ribavirin (4.7%) or sofosbuvir/daclatasvir and ribavirin (6%).
Virological monitoring during treatment showed that viral
load changes closely resembled those reported in clinical trials of the
combinations used by patients. SVR4 data are available for 139 patients who
have completed treatment and undergone viral load testing four weeks after completing
The overall sustained virological response rate four weeks
after completion of treatment (SVR4) was 94.4%. In genotype 1 patients treated with
sofosbuvir/ledipasvir, 93.2% achieved SVR4 and 97.4% of those who received
sofosbuvir/daclatasvir achieved SVR4. Ninety per cent of the 29 patients with
genotype 3 achieved SVR4, and 100% of those with genotypes 2 (n = 6), 4 (n = 3) and
5 or 6 (n = 2) achieved SVR4.
One case of viral breakthrough during treatment occurred. Four deaths occurred during the
study, all due to hepatocellular carcinoma. The remaining virological failures
were virologic relapses after the completion of treatment.
Virological responses four weeks after the completion of
treatment did not differ substantially from those observed 12 weeks
post-treatment in clinical trials of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir,
where rates of sustained virological response ranged from 90% in genotype 3 to 96%
in genotype 1.
No previously unreported side-effects were observed.
Headache, nausea and fatigue were the most commonly reported adverse events.
Three people with
compensated cirrhosis temporarily decompensated after treatment initiation but
continued their courses of treatment.
studies are underway to generate more information on the use of generic
products in the full range of genotypes found worldwide. “It won’t be long
before the [size of the] datasets for generics surpass those produced by
companies,” said Dr Freeman.
He warned that anyone seeking to obtain medication from generic producers should look for reputable manufacturers and should be monitored by a doctor. The FixHepC website contains details of how to identify reputable suppliers, how to import medicines legally into Australia, the United Kingdom and New Zealand, and details of how to join the REDEMPTION cohort study.
findings were greeted positively by the European Association for the Study of
the Liver (EASL), the organiser of the International Liver Congress.
“There is a clear role for generic treatments such as these
for people with hepatitis C across the world. The implications of increased
availability of these drugs could be enormous, presenting more people with the
possibility of a ‘cure’ for what is often a debilitating condition,” said
Professor Laurent Castera, EASL Secretary General.