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EASL 2016: Low-Cost Generic Hepatitis C Drugs Match Branded Products in Viral Response

Generic versions of direct-acting antivirals for hepatitis C 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 European Association for the Study of the Liver's International Liver Congress (EASL 2016) in Barcelona on Saturday.

[Produced in collaboration with Aidsmap.com]

The study presented preliminary data on sustained virological responses 4 weeks after the completion of treatment, known as SVR4. The "gold standard" measurement of cure for 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 4 weeks after completion of treatment.

The high cost of branded direct-acting antivirals (DAAs) 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 (original brand name Sovaldi), sofosbuvir/ledipasvir Harvoni), and daclatasvir (Daklinza).

Importation of medicines for personal use is permitted under customs regulations in Australia and the U.K., 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 Southeast Asia.

Freeman, a doctor based in Hobart, Tasmania, started to take an interest in how to treat patients safely with generic DAAs 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. 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 quantities.

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 DAAs to buy products from reputable suppliers in India, in order to reduce risks in the supply chain.

In January 2016 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 (NCT02657694).

Treatment used in this study cost between $1400 and $1600 for a course of medication, compared to a cost of up to $84,000 for Sovaldi and $94,500 for Harvoni in the U.S. Prices of generic products manufactured in India are likely to fall further, possibly as low as $200 per course of treatment, as production increases.

The findings presented at the International Liver Congress are virological response data 4 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 hepatitis C treatment, 31.3% 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 plus ribavirin (4.7%) or sofosbuvir/daclatasvir plus ribavirin (6.0%).

Virological monitoring during treatment showed that viral load changes closely resembled those reported in clinical trials of the branded combinations used by patients. SVR4 data were available for 139 patients who have completed therapy and undergone viral load testing 4 weeks post-treatment.

The overall SVR4 rate was 94.2%. Among genotype 1 patients treated with sofosbuvir/ledipasvir, 93.7% had a sustained response at post-treatment week 4 and 97.4% of those who received sofosbuvir/daclatasvir achieved SVR4. 90% of the 29 patients with genotype 3 achieved SVR4, as did 100% of those with genotypes 2 (n=6), 4 (n=3), and 5 or 6 (n=2).

One case of viral breakthrough during treatment occurred. There were deaths during the study, all due to hepatocellular carcinoma. The remaining virological failures were relapses after the completion of treatment.

Virological responses 4 weeks after the completion of treatment did not differ substantially from those observed at 12 weeks post-treatment in clinical trials of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir, where SVR12 rates ranged from 90% for genotype 3 to 96% for genotype 1.

No previously unreported side effects were observed. Headache, nausea, and fatigue were the most commonly reported adverse events; 3 patients with compensated cirrhosis temporarily experienced decompensation after treatment initiation but continued their courses of therapy.

Further 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 Freeman.

Freeman 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 U.K., and New Zealand, and details of how to join the REDEMPTION cohort study.

The findings were greeted positively by audience and by the European Association for the Study of the Liver, the organizer 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 EASL Secretary General Laurent Castera.

4/16/16

Reference

J Freeman, R Sallie, A Kennedy, et al. High sustained virological response rates using generic Direct Acting Antiviral treatment for Hepatitis C, imported into Australia. EASL International Liver Congress 2016. Barcelona, April 13-17, 2016. Abstract LB03.

Other Source

EASL. Low-cost generic direct-acting antiviral treatment for hep C is equivalent to branded formulations. Press release. April 16, 2016.