Generic DAAs achieve excellent cure rates in Egypt matching those of branded drugs at a fraction of the cost

Michael Carter
Published:
01 February 2019

Generic direct-acting antivirals (DAAs) are just as effective and safe as their branded equivalents for the treatment of chronic hepatitis C virus (HCV) infection, according to Egyptian research published in Liver International.

Generics achieved a cure in 98% of patients and a course of treatment cost between $85 and $141, well below the price of discounted branded medication and making eradication of HCV in Egypt – which has the highest HCV prevalence in the world – an achievable goal.

The retrospective research involved 648 people in Alexandria who were treated with generics between January 2016 and May 2017. Treatment-experienced and treatment-naïve individuals were eligible for inclusion, so too were individuals with liver cirrhosis.

Participants received one of two combinations of generic DAAs, in half of cases with the addition of ribavirin. Outcomes for both regimens were comparable to those achieved with branded medication. The non-response rate was below 1% and only eight people stopped therapy – in each case due to the development of liver cancer. No serious adverse events were reported and the most commonly reported side-effect – anaemia – was due to ribavirin.

“Generic direct-acting drugs used in treating patients with HCV GT [genotype] -4 demonstrated equal potency, safety and tolerability compared to original brands, with low cost which would help provide treatment to a large scale of patients,” comment the authors.

Approximately 10% of the Egyptian population has chronic HCV infection and 95% of these individuals carry HCV genotype 4.

Treatment of HCV has been revolutionised by the development of oral DAAs, which achieve cure rates well in excess of 90% across genotypes.

DAAs approved in Egypt for treatment of HCV genotype 4 include sofosbuvir (SOF), ledipasvir (LDV) and daclatasvir (DAC), used in combination and with or without ribavirin (RBV).

Egypt is a low-middle income country and can only afford generic DAAs.

Investigators in Alexandria wanted to see if DAAs were effective and safe for the treatment of genotype 4. They therefore retrospectively analysed outcomes in people treated with SOF/LDV or SOF/DAC, with or without ribavirin. People received treatment per European guidelines for 12 or 24 weeks.

Data were collected on rates of cure (sustained virological response 12 weeks after the completion of treatment, SVR12), treatment failure, relapse, discontinuations, serious adverse events and side-effects.

Most of the people (488) were taking HCV therapy for the first time, and 160 had taken a previous unsuccessful course of treatment. The treatment-naïve participants had a mean age of 54 years, half were men and 56% had liver cirrhosis. Treatment-experienced individuals were comparable in terms of age, but 85% were male and 55% had cirrhosis.

Approximately three-quarters of the treatment-naïve group received SOF/DAC, the remaining people taking SOF/LDV. Eighty per cent of treatment-experienced people received SOF/DAC, the other 20% treated with SOF/LDV. Just under half (45%) of individuals took ribavirin.

The overall SVR rate was 98%. A non-response was observed in 0.6% of people, relapse occurred in two people (0.3%) and eight participants (1.3%) stopped therapy early, each case due to the development of liver cancer.

All treatment-experienced people had an SVR12, as did 97% of treatment-naïve individuals (100% of people without cirrhosis, 95% of people with cirrhosis).

Comparison of the two regimens showed that 96% of individuals taking SOF/LDV and 98% of individuals on SOF/DAC had an SVR12. Both regimens were equally effective, regardless of previous HCV treatment history.

Only people with cirrhosis received ribavirin, and response rates did not differ significantly according to its use (100% vs 98%).

The only significant difference between the two regimens was SVR12 rates in people who received SOF/DAC and ribavirin and those who received SOF/LDV and ribavirin (100% vs 88%, respectively, p < 0.001).

No drug-related serious adverse events were recorded. Anaemia developed in 9% of people, in each case due to ribavirin, and was successfully managed.

Average treatment costs of SOF/DAC and SOF/LDV were $85 and $141, respectively. The authors note that a single course of therapy with branded medications, even with a substantial drug company discount, would cost in the region of $1500.

“These prices are all very expensive and would not have helped to treat a large number of patients due to its high burden for health care systems as well as for the patients,” they write. “So the only solution was to introduce low-cost generic drugs with the same efficacy and safety into the market. In our study, we demonstrated that the Egyptian generic DAAs succeeded to achieve this target.”

Reference

Lashen SA et al. Tolerability and effectiveness of generic direct-acting antiviral drugs in eradication of hepatitis genotype 4 among Egyptian patients. Liver Int, doi: 10.1111/liv.14022, 2018.