October 23, 2013

Preview - New wave of oral hepatitis C drugs near U.S. approval

By Deena Beasley
Wed Oct 23, 2013 10:08pm IST

(Reuters) - Patients infected with the liver-destroying hepatitis C virus should soon have better treatment options as new tablets from Gilead Sciences and others approach U.S. regulatory approval.

Gilead's experimental drug sofosbuvir is the first of a new wave of oral therapies to be considered by the Food and Drug Administration, which has convened an advisory panel for Friday.

The treatment is seen as the crown jewel of Gilead's $11 billion purchase of biotechnology company Pharmasset and aims to replace some of the pills and injections now on the market.

"Treatment will become simpler, shorter and safer ... a broader group of patients can be treated," said John McHutchison, head of liver disease therapeutics at Gilead.

In a pre-hearing report issued on Wednesday, FDA staff concluded that sofosbuvir is safe and effective as part of a combination regimen for hepatitis C.

The deadline for a regulatory decision on the drug is December 8. Wall Street analysts have forecast sales of $1.85 billion next year, assuming a price of $85,000 per patient, according to ISI Group. Hepatitis C affects around 3.2 million Americans, killing more than 15,000 each year, mostly from illnesses such as cirrhosis and liver cancer.

The standard treatment has long been a combination of interferon, given by injection, and ribavirin, a pill. But both drugs have side effects and neither works directly against the virus. In addition, the regimen is not that effective for many people living with hepatitis C, especially those with hard-to-treat genotype 1 infections.

Technological advances over the past decade have enabled the development of direct-acting antivirals (DAAs) that specifically target the hepatitis C virus. Two new antiviral drugs, Incivek from Vertex Pharmaceuticals Inc and Victrelis from Merck & Co, have cured more HCV patients in recent years, but both are protease inhibitors and are still used in combination with interferon and ribavirin.

Protease inhibitors are designed to block certain enzymes the virus needs to replicate.

Gilead's drug is part of a new class known as nucleotide analogue inhibitors, or "nukes," designed to block a different enzyme the virus needs to copy itself. The company says the therapy is more difficult for the body to overcome, and expects treatment times to be shorter and easier to endure. It has first sought FDA approval to use sofosbuvir along with ribavirin as an all-oral therapy for genotype 2 and 3 infections, or about 28 percent of the U.S. hepatitis C patient population.

It is also seeking approval to use the drug in combination with both ribavirin and interferon for more common genotype 1 infections, while planning for file next year for an all-oral treatment regimen for those patients.

"We have a very, very high barrier to resistance," McHutchison said.

He estimates that around 70 percent of U.S. HCV patients have genotype 1, up to 20 percent are infected with genotype 2, and 8 percent have genotype 3.

COMPETITIVE ADVANTAGE?

Gilead is the world's largest maker of branded drugs to treat HIV, the virus that causes AIDS, but has turned to hepatitis C treatments to diversify its pipeline.

"Before we acquired Pharmasset we did a lot of due diligence," McHutchison said. "I think we picked the right nuke."

Sanford Bernstein analyst Geoffrey Porges believes Gilead's advantage over competitors in the HCV field may be increasing as it becomes more clear that a nuke-based regimen has fewer limitations in terms of dosing convenience and breadth of genotype effectiveness.

"We are approaching an inflection point for hepatitis C for Gilead," he said.

It is a competitive field, and there have been setbacks for some. Vertex said in July that the FDA had placed a partial hold on a mid-stage study of its experimental hepatitis C nuke. Bristol-Myers Squibb last year discontinued development of one of its experimental drugs after a patient died of heart failure during a clinical trial and several others were hospitalized.

While Gilead is perceived to be in the driver's seat in the race to produce all-oral treatments, Bristol-Myers is expected to present Phase III data on an interferon-free treatment for genotype 1 patients at next month's meeting of the American Association for the Study of Liver Diseases in Washington D.C.

That regimen will consist of daclatasvir, which blocks a protein called NS5A that plays a key role in HCV replication, that Bristol-Myers sees as the backbone of its hepatitis program, along with its protease inhibitor asunaprevir.

Bristol plans to begin pivotal testing of a three-pill therapy early next year. Companies like AbbVie and Boehringer Ingelheim are also spending millions to develop new hepatitis C treatments.

McHutchison said data on another Gilead all-oral regimen - sofosbuvir combined with NS5A inhibitor ledipasvir - will be presented at a medical meeting next April. The company plans to file for FDA approval of that regimen, which includes genotype 1 patients, in the first half of next year.

He said sofosbuvir has so far been tested in more than 3,000 patients and there have been no issues with heart problems or other side effects beyond those associated with the drugs it has been combined with.

Earlier trials of the company's all-oral combination for genotype 1 resulted in more than 95 percent of patients being cured, McHutchison said.

The FDA advisory committee will also hear comment this week on Johnson & Johnson's application to sell simeprevir, an experimental protease inhibitor designed to target genotype 1 HCV.

(Additional reporting by Bill Berkrot; Editing by Krista Hughes)

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