Treatment with generic versions of direct-acting antiviral drugs (DAAs) for hepatitis C continues to produce similar cure rates to those reported in clinical trials of brand-name drugs, James Freeman reported last month at the EASL International Liver Congress in Amsterdam.
Freeman, an Australian general practitioner based in Hobart, Tasmania, reported on outcomes among people with hepatitis C who imported generic versions of direct-acting antivirals manufactured in India and elsewhere because they couldn’t afford treatment in their own country, or were denied treatment on the ground of cost.
Importation of medicines for personal use
This 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 Southeast Asia.
At last year’s International Liver Congress Freeman reported on sustained virological response at 4 weeks after the end of treatment (SVR4) for 139 people who had imported generic DAAs to their own countries and who provided laboratory-confirmed results of HCV RNA monitoring and other medical information during and after their treatment. SVR4 is not yet a cure, as relapses can still happen after this point, but undetectable HCV RNA at 12 weeks post-treatment (SVR12) is considered a cure.
At this year’s meeting Freeman reported sustained virological response data for 448 patients, including the 139 people included in last year’s preliminary report.
Participants included in the study cohort
Lived mainly in Australia, New Zealand, the U.S., and the European Union, although the cohort also included a large cluster of patients in Nigeria.
Participants were treated predominantly with sofosbuvir plus ledipasvir, the drugs in Gilead Science's Harvoni coformulation (51%), or sofosbuvir plus daclatasvir (49%), using products manufactured in India or Bangladesh. A small proportion added ribavirin to their combination, and 0.9% took sofosbuvir and ribavirin alone.
The cohort included a high proportion of treatment-experienced people (42%), and 28% had cirrhosis. Over half (57%) were male, with a mean age of 55 years. Participants had a high mean baseline HCV RNA (6.47 log IU/mL). Genotype 1 HCV predominated (67%), but a sizeable proportion (23%) had genotype 3 and a smaller proportion had genotype 2 (6%).
Although HCV RNA measurements were carried out by different laboratories, using a lower limit of quantification of <25 IU/mL as the measure of virological response, 85.7% of participants achieved rapid virological response 4 weeks after starting therapy and 99% an end-of-treatment response. The sustained virologic response rate four weeks post-treatment (SVR4) was 94% and the SVR12 rate was 90%. Only 2 patients out of 448 were lost to follow-up.
Post-treatment virological relapse was most evident in people with HCV genotype 3; only 82% of genotype 3 patients (83 of 101) achieved SVR12, compared to 91% with genotype 1 (275 of 301), 100% with genotype 2 (28/28), 91% with genotype 4 (10/11), and 100% of those with genotypes 5 or 6 (7/7).
Freeman blamed under-treatment for many cases of relapse, for genotype 3 patients especially. Viral load appeared to decline more quickly in genotype 1 patients treated with sofosbuvir plus daclatasvir compared to those with genotype 3, leading Freeman to suggest that even in previously untreated genotype 3 patients without cirrhosis, 16 weeks of sofosbuvir plus daclatasvir may be necessary to achieve a cure.
The risk of relapse or treatment failure was clearly predicted by virological response after day 24. If a patient still had a detectable HCV RNA beyond this point, they were twice as likely to fail to achieve SVR12 (odds ratio 1.91). Freeman suggested that intensifying treatment at this time for those with a detectable HCV viral load, would be more cost-effective than assembling a salvage regimen.
Cirrhosis at baseline was similarly predictive of a failure to achieve SVR12 (OR 1.92). Freeman observed that 10 patients with cirrhosis were prescribed 12-week courses of treatment, only 2 of them with ribavirin.
Freeman also provided a snapshot of results from 3 other cohorts of patients in Eastern Europe, South East Asia, Europe, and North America who are obtaining generic direct-acting antivirals. So far, an additional 229 patients have reached the 12-week post-treatment follow-up point; of these, 222 have achieved a sustained virological response, representing a cure rate of 97%.
Freeman reminded delegates that the majority of people treated for hepatitis C worldwide received generic versions of DAAs, and that the use of generics will accelerate as more countries begin to provide hepatitis C treatment. Egypt alone has treated more 1 million people.
But for at least 51% of the world’s population with hepatitis C, an affordable cure for hepatitis C remains out of reach, he said, due to patent barriers.
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