Published online 13 August 2010 | Nature | doi:10.1038/news.2010.408

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Boost for drugs against hepatitis C

Promising clinical trial results point to the pharmaceutical industry's next blockbuster.

Hepatitis virus particlesHepatitis virus particles: drugs targeting hepatitis C could make billions of dollars, say analysts.AMI IMAGES / SCIENCE PHOTO LIBRARY

A new generation of drugs with the potential to cure hepatitis C is set to flood the market.

This month, Vertex Pharmaceuticals, based in Cambridge, Massachusetts, and drug behemoth Merck, headquartered in Whitehouse Station, New Jersey, both released promising results from late-stage clinical trials of their leading drugs against hepatitis C virus (HCV).

The two treatments belong to the first wave of what pharmaceutical analysts think will be a profusion of HCV-targeting drugs that could ring up billions of dollars in annual sales. "There certainly is blockbuster potential for new and efficacious drugs in hepatitis C," says Hedwig Kresse, a drug-market analyst at Datamonitor in London.

The virus infects liver cells and can cause cirrhosis and liver cancer. It affects about 3% of the world's population — and new treatments are urgently needed.

"There are a lot of people who don't respond to the current therapies or are unable to tolerate them," says Paul Klenerman, who works on hepatitis C therapies at the University of Oxford, UK. "There's no doubt there's a big unmet need there."

Currently, patients spend about a year taking a combination of interferon-α, a protein that boosts the immune system, and ribavirin, an antiviral drug that does not specifically target HCV. Roughly half of all patients with hepatitis C are cured by this course, but it can also cause serious side effects, such as depression, anaemia, and flu-like illness.

Protease punch

Enter Vertex's drug telaprevir and Merck's boceprevir. Both block HCV's protease enzyme so that it cannot carry out one of its key tasks. All of HCV's proteins are initially produced as one long polyprotein, which needs to be cleaved into its component proteins by the protease. Blocking the protease prevents the virus from producing functional proteins.

The companies will submit their medicines to the US Food and Drug Administration by the end of this year, with an eye towards approval in mid-2011.

Data released this month fulfil the pharmaceutical industry's high expectations for the effectiveness of these drugs. Boceprevir, combined with interferon-α and ribavirin, cured the infections of about two-thirds of the patients who followed a 48-week course, Merck announced on 4 August. Some patients were able to finish the course even sooner, at 28 or 36 weeks.

Telaprevir, also combined with the standard drugs, cured 72% of patients after just 24 weeks of treatment, Vertex said on 10 August. Patients who responded quickly to the drug, within 4 to 12 weeks, were the most likely to be cured by it. Another phase III trial of telaprevir, the results for which Vertex released in May, had already demonstrated the benefits of the 24-week course, but the latest study confirmed that it was just as effective as a 48-week regimen for most patients.

"This is such a huge step forward. You can't call it one step — it's multiple steps with one drug," says Stefan Zeuzem, a professor of medicine who studies hepatitis C at Johann Wolfgang Goethe University Hospital in Frankfurt, Germany.

Analysts are already giving telaprevir the edge, largely because of the shorter course of treatment. Peter Chang, a scientific analyst at Sagient Research Systems in San Diego, California, estimates that sales of telaprevir could reach US$6 billion a year across the United States and Europe by 2014. Vertex is developing the drug in collaboration with the pharmaceutical companies Tibotec Pharmaceuticals, based in Ireland, and Mitsubishi Tanabe Pharma, based in Japan.

Cocktail approach

If approved, telaprevir and boceprevir will take the early lead in an HCV drug field that could grow to be worth $15 billion by 2017, according to Irena Melnikova, a life-sciences analyst at TVM Capital in Boston, Massachusetts. The field is poised to become even more crowded in the coming years. "There are still going to be a number of patients who fail [to be cured by] telaprevir or boceprevir," says Chang. "There's plenty of market to still go after."

Other companies are also developing protease inhibitors, as well as drugs that target other parts of the virus. The main targets apart from the protease are HCV's polymerase enzyme, which copies its RNA genome, and its NS5A protein, which is involved in replication and viral assembly but is not an enzyme. Drugs targeting these proteins are now in phase I and II trials.

Experimental drugs targeting different parts of the virus should also stymie the development of drug-resistant strains of HCV. The approach would be similar to the one taken against HIV, for which patients take a cocktail of drugs.

With vaccines that would prevent HCV infection still in early stages of development, the next-generation drugs will be vital for curing those who are affected. For now, the protease inhibitors being developed will be combined with interferon-α and ribavirin. But Klenerman says that "once we have more agents we will have room to design some interesting therapies".

Pharmaceutical firms are already testing different combinations of drug candidates to see what works best for different patients. "Ultimately, we should have a cocktail allowing viral eradication for every patient," says Zeuzem. 

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