Hepatitis C virus (HCV) treatment has now entered a new era, with new direct acting antiviral (DAA) oral drug combinations, demonstrating greater than 90% clearance (HCV cure), even in people with cirrhosis, and affording the same efficacy in people coinfected with HIV.
Although these new DAA treatments have now become available in various parts of the world, including the US and Europe, they are yet to be listed on the Australian Pharmaceutical Benefits Scheme (PBS). Nonetheless, the PBS listing is expected to occur soon (when pricing of the drugs is agreed with the Commonwealth), as there is a high clinical need for all oral (pill only) interferon-free treatment for chronic hepatitis C.
For a long while the standard treatment for HCV has involved weekly injections of interferon, plus a twice daily ribavirin (pill) for 24 or 48 weeks. Clearance of HCV was possible on this dual treatment – although much less than the new DDAs offer – at about 60-70% success rate, but also less than that for people with HIV/HCV coinfection. Interferon plus ribavirin side -effects were intolerable for many, and needed to be persevered with and co-managed for up to one (1) year of the treatment. Over the last few years other drugs (Protease Inhibitors – boceprevir and telaprevir) were added to these standard therapies, which improved Hepatitis C clearance outcomes (especially for harder to treat genotype 1), but they also added to side-effects, had many drug interactions, and still required a 24 week to 48 week treatment schedule. This is also the same situation with the most recent addition of simeprevir (which replaced telaprevir and boceprevir) but still requires 6 months to 12 months treatment.
Currently simeprevir (Olysio) is the only available (in Australia) and recommended treatment for use in combination with interferon and ribavirin. Simeprevir has been studied in combination with the new DAA drugs (which await approval on the PBS) and will continue to be used in combination with these new agents should they arise on the PBS, as they have in other parts of the world.
It is a clinical imperative these new DDAs achieve an urgent PBS listing due to their wide efficacy for many genotypes (known as “pan-genotypic”) and high effectiveness to clear HCV (>90%), including the great advance of much shorter 12 week treatment duration (24 week max). The new DDA treatments awaiting PBS listing are:
- sofosbuvir (Sovaldi);
- ledipasvir and sofosbuvir combined in one pill (Harvoni), and
- daclatasvir and sofosbuvir as 2 separate pills (Daklinza and Sovaldi).
These ‘blockbuster’ effective new pill-based HCV medications are also enticing further new entrant drugs to the market, in order to overcome variable drug interactions (for example with HIV medications) and some reduced options for certain genotypes or stage of HCV disease, even while these new medications provide “cure” for the majority of people with hepatitis C already.
A further new entrant treatment (Viekira Pak), known colloquially as “3D” due to its triple drug combination – ombitasvir, dasabuvir and paritaprevir (boosted with ritonavir), will be considered by the Pharmaceutical Benefits Advisory Committee (PBAC) in July 2015 for treatment of hepatitis C genotype 1 and the outcome for its PBS listing is expected in late August 2015. This treatment has been studied in HIV/HCV (genotype 1) co-infected people in the Turquoise-1 Study and has shown 92 percent (58 out of 63) of the participants had an undetectable hep C viral load at week 2. Among those treated for 12 weeks, 94 percent (29 out of 31) achieved a sustained virologic response 12 weeks after completing therapy (SVR12, considered a cure)1,2.
The other present DAAs awaiting PBS listing have also been studied in HIV/HCV co-infection trials, and have demonstrated equally effective responses to these new treatments as people with HCV mono-infection only; including people who have not previously responded to (current) interferon-based treatments for HCV. There are, however, particular guidelines for special guidance for managing HIV drug interactions with HCV treatments, either through switching HIV medications or altering doses and these require special considerations by the treating doctor. Nonetheless, these new interferon-free HCV treatment options are many and exciting, and this expansion of the pipeline will soon bring about HCV cure for the majority – signifying the commencement of the virtual elimination of HCV in the very near future when new HCV drug access is universal, which also makes it cost effective to the world by averting new infections.