The standard combination drug treatment of pegylated interferon and ribavirin has been a qualified success. Whilst it is a definite improvement on previous treatment approx 50% of those treated (depending on genotype) still do not clear the virus. The side effects for some people can be debilitating and sometimes intolerable and are the cause of a number of people stopping treatment . It is also expensive. There is an urgent need for more effective and better tolerated treatments.
This is particularly the case for the growing number of people for whom treatment has not been successful and for those with a lower chance of achieving a sustained virologic response (SVR).
- Those with genotype 1 and a high viral load
- People with advanced liver damage (compensated and decompensated cirrhosis)
- Those co-infected with HIV/HCV
- Previously treated non-responders
- Those who have relapsed
- Liver transplant recipients, virtually all of whom develop recurrent HCV infection.
The high prevalence of HCV infection in the developed world means that it is potentially a highly lucrative market for pharmaceutical companies so a great deal of research time and money is being spent on new HCV therapies. There are currently about twenty-four treatments in trial. Some are monotherapies (drugs or therapies taken on their own) and some are for use in conjunction with existing HCV treatments. Some of these developmental treatments have shown promising results in clinical trials. Two drugs currently undergoing trials have been given fast track status by the FDA (Food and Drugs Administration) in the USA. These are Telaprevir (VX 950 - Vertex) and SCH 503034 (Boceprevir - Schering Plough) . Fast track status is only ascribed to drugs in development that the FDA thinks have the potential to address serious, unmet medical needs. The review process for these drugs is faster. The pharmaceutical company and the FDA have frequent meetings to track the progress of a particular drug. If any drug fulfils it promise it may then be given priority for consideration to be licensed for use by doctors. Based on the progress Telaprevir is making in trials it is possible that the drug will be available for clinical use in the USA by 2010/11. Boceprevir's progress has been a little slower and so if successful will take longer to be available for clinical use. Both of these drugs are protease inhibitors, treatments that aim to prevent HCV from replicating.
Protease inhibitors have been a major breakthrough in the treatment of HIV/AIDS. In treating HCV infection they offer the promise of improved responses and shorter treatment regimes. However, HIV rapidly develops resistance to these drugs, which is why drugs have to be taken in powerful combinations. It is likely that this will be the case with HCV. The very structure of HCV makes it highly prone to mutation and so capable of developing strains that may be resistant to certain drugs. This means that combinations of multiple drugs, possibly targeting both the virus and the human immune responses, will likely be required to treat chronic HCV infection effectively.
Developing a drug is a lengthy and uncertain process. It can take ten to fifteen years from the initial concept to a drug finally becoming licenced. The percentage of drugs that actually make it onto the market is also very small. This is due to the many pitfalls on the way. Treatments that show initial promise in the laboratory may often have little or no effect when tested in animals or in human clinical trials or drugs may prove to have dangerous or intolerable side-effects that only become apparent much later in trials. In fact, only one in 1,000 compounds makes it to human testing. Of those drugs that make it to human testing only 1 in 5 will be licensed by the regulatory authorities for use in surgeries and clinics.
Whilst there is a lot of promise that there will be new treatments for HCV in the near future it is still only promise. Peg-interferon/ribavirin will continue to be the mainstay of treatment for some time, particularly as the treatments closest to being licenced will be used in combinaton with interferon and ribavirin. So, alongside the search for new treatments improving the effectiveness and tolerability of inteferon-based treatments is also a vital area of research.
At present research into new HCV treatments is predominantly focused on three approaches:
1. Treatments that target the virus
The main emphasis has been on targeting particular stages in the life cycle of the virus to stop it being able to replicate. There are two main areas of research in this field. Drugs or therapies that try and block particular proteins on the virus. These drugs are known as protease or polymerase inhibitors and are designed to stop the virus from being able to replicate by interfering with specific viral proteins. The other area of research is drugs that try to interfere with the genetic structure of the virus.
2. Treatments that boost the human immune response to HCV
These are known as immunomodulatory treatments. Interferon based therapies have shown that that HCV infection can be cleared by stimulating the immune response to the virus. Various drugs are being trialled aimed at boosting the immune response. There is also research into making a therapeutic vaccine, which, in theory, will also bolster the immune response. Therapeutic vaccines are a new approach to vaccines. They are designed to treat people who are already infected with HCV. A preventive or prophylactic vaccine against hepatitis C is also being researched, though a viable preventive vaccine is probably many years away.
3. Modifications to interferon based treatments
There are numerous trials taking place studying different treatment regimes for peg-interferon/ribavirin such as variations in dosage and length of treatment. For details of these trials see Retreatment
