The first new DAAs for hepatitis C are Vertex Pharmaceuticals' (VRTX) Incivek and Merck's (MRK) Victrellis. Both of these drugs are "protease inhibitors," which means they block the enzyme protease that the virus needs to make copies.
Protease inhibitors, or PIs, are very potent drugs, meaning they work quickly to tamp down a lot of virus. In studies, many patients taking a PI are able to reduce their viral load, or the amount of virus in their system, to undetectable levels within a month or less.
PIs have drawbacks, however. These drugs have a low barrier to viral resistance, which means the hepatitis C virus can mutate or change so that a PI is no longer effective. In studies, patients may initially respond very well to a PI but after awhile, mutated virus left in the body starts to replicate and the patient's viral load rebounds.
For this reason, PIs cannot be used alone to treat hepatitis C. Instead, they must be given with other antiviral drugs. Both Incivek and Victrelis, for instance, must be administered in combination with interferon and ribavirin. The big upside with the triple combination is a dramatic improvement in cure rates (up to 80% from 40-50%) and shorter treatment duration (six months instead of one year.)PIs tend to cause more side effects, partly due to the way they react with other drugs. Incivek's most common side effect, for example, is a serious rash. The first generation of PIs also work mainly in patients with the genotype 1 form of hepatitis C, which represents about 70% of cases in the U.S. and is generally more difficult to treat. Newer PIs, including a drug developed by Achillion Pharmaceuticals (ACHN), are designed to be "pan-genotypic," meaning they will work in patients with other hepatitis C genotypes (Type 2, Type 3, etc.) that are more common in other parts of the world. The newer PIs are also a more convenient once-daily dosage. Nucleoside (or nucleotide) polymerase inhibitors -- "nucs" for short -- is the other major hepatitis C drug class you'll hear most about and is the current class of drugs getting the most attention from Wall Street. Pharmasset (gobbled up by Gilead Sciences (GILD) for $11 billion), Inhibitex (INHX) (soon to be acquired by Bristol-Myers Squibb for $2.5 billion) and Idenix Pharmaceuticals (IDIX) (still independent but for how long?) are all developing nucs.
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