Numerous pharmaceutical companies are in the process of developing new medications to treat Hepatitis C.  However, there are many years that go into this process.  When these companies come up with the idea of developing a new drug, strict standards come into play.  There are several phases a new drug must go through before it has FDA approval.  
These phases consist of :

*pre-clinical or animal development

*Phase 1-a new drug is tested in a small group of healthy individuals to evaluate its safety, determine a dose range and identify side effects

*Phase 2- the new drug is given to a larger group of people who have been diagnosed with whatever disease process is being studied.  The drug’s safety, best dose range and its effectiveness will be tested.

*Phase 3- The drug is given to a large group of people with the disease that is being studied. This phase is designed to gather the additional information about how effective and safe the drug is compared to the risks it may have.

*Phase 4- the drug has already been approved and is available, but is being tested for another indication (i.e. originally prescribed for a rash, now being tested for preventing ulcers)

Development of a new drug can take 12 years before it is available to the general public.  According to the FDA website, the timetable is as follows:
Pre-clinical testing        1-3 years (average 18 months)
Phase 1-3                     2-10 years (average 5 years)
NDA review                   2 months-7years (average 24 months)
(New Drug Application)

Several new drugs for the treatment of Hepatitis C were discussed at the AASLD (American Association for The Study of Liver Diseases) meeting.  The most promising new medications are the protease and polymerase inhibitors.  These medications are designed to inhibit the enzymes needed for Hep C virus replication. One of the protease inhibitors under study is Telaprevir (Vertex).  It has shown great promise in patients that are treatment naïve (that is, have never been treated for Hepatitis C) and are currently under study for patients that have been treated and didn’t respond or relapsed to treatment.  The results have been promising during the initial 24 weeks of therapy for non-responders and relapsers.

Another protease inhibitor under study is Boceprevir (Schering-Plough).  Studies are ongoing for both treatment naïve and treatment experienced patients.  Preliminary data from studies in the naive population show the drug is safe for up to 48 weeks, and when taken in combination with Peg/RBV for 48 weeks the sustained viral response (SVR) doubles.

Another type of therapy discussed was immunotherapy.  These types of drugs active the immune system to accelerate the elimination of HCV infected cell during treatment with PegIFN/RBV.  An interim 4 week report of Tarmogen GI-5005(GlobeImmune) doubled viral clearance overall and in all major subgroups and doubled the rapid virologic response (RVR) rate in naïve patients with high viral load. The study compared GI-5005 plus standard of care (SOC) -- pegylated-interferon plus ribavirin -- versus SOC alone in patients with chronic genotype 1 hepatitis.

Roche , InterMune and Pharmasset have come together with the first dual-combination clinical trail with oral antivirals in Hepatitis C.  This study will combine a protease inhibitor and a polymerase inhibitor (NO interferon!)  This study is currently being conducted in Australia and New Zealand.

It is important to keep in mind that even though these preliminary data are promising, these medications are not without side effects.  In the case of telaprevir, the main adverse events were rash, anemia, pleuritis, itching, fatigue and depression.  The main adverse events for Boceprevir were higher anemia, low white blood cell count, an altered sense of taste, myalgia and itching.  Lastly, Tarmogen GI-5005 adverse events were redness around the injection site, fatigue and headache.

Data from the IDEAL trial (Schering-Plough) demonstrated the significance of the early viral response to medication.  It was found that if someone has a significant drop of their viral count or an undetectable viral count after 4 weeks of therapy, they had a greater than 61% probability of Sustained Viral Response.  Those people who had little or no decrease in their viral count after 4 weeks of therapy has a less than 5% probability of a sustained viral response.


****Our gratitude to Dr. Marsano's office for this report.  Dec., 2008