Medical Health Encyclopedia

The combination of pegylated interferon alfa-2b with ribavirin (Rebetol) has achieved the best success rates to date of all interferons and their combinations. It has achieved responses of up to 51% with genotype 1 and nearly 80% with genotype 2 and 3. According to a 2002 comparison study, the Pegasys combination may even produce better results.

PegINF combinations are proving to slow progression of scarring, and have even achieved improvement in some patients who already have cirrhosis. Whether the combination treatment protects against future liver cancer is still unclear. (A higher total dose, rather than a longer duration of treatment, may be the critical factor for protection.)

Investigative Drugs for Hepatitis C

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The current drugs used for HCV still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Some showing promise include the following:

• Nucleoside analogs. Several new nucleoside analogs are in clinical development. Viramidine is a drug related to ribavarin. It is being studied in Phase III trials alone and in combination with pegylated interferon-alfa. Valopicitabine (NM283) is being tested in Phase II trials as alone and in combination with pegylated interferons.
• Albuferon. This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in Phase II trials for patients who have not been treated with or have not responded to standard interferon-alfa.
• IMPDH Inhibitors. Mycophenylate mofetil and VX-497 are agents that inhibit an enzyme known by its brief name, IMPDH, which may block replication of the hepatitis C virus. If effective, they would most likely be used in combination with interferon and ribavirin.
• Amantadine (Symmetrel) is an anti-viral agent being investigated in various combinations. For example, triple therapy with amantadine, pegylated interferon, and ribavirin is showing particular promise. In some cases, the side effects of amantadine can be severe, and include vertigo, insomnia, nervousness, and depression. They are particularly disabling among older patients who receive inappropriately high doses.
• Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors call T-cells). It is being used for hepatitis B and is under investigation for hepatitis C in combinations with natural interferons and pegylated interferon.
• Protease Inhibitors. Novel protease inhibitors (similar to those used for HIV) are under investigation for hepatitis C patients who fail other treatments. These agents are based on molecular therapies that target proteins involved in viral reproduction.