Cartoon from the futureThere's never been anything quite like this. The latest ripple effect of the 1945-65 baby boom will be a drug bill so high, that paying it, says Australia's advisors, "is not possible."

How high is this bill going to be? One drug, sofosbuvir (Sovaldi), approved by the FDA last December, reached sales of $5.8 billion by June.

And it's set to escalate dramatically today, now that the FDA approved a new drug as expected. It's called Harvoni, and it's a combination of sofosbuvir and a new drug, ledipasvir. Far more is likely to be spent on this one - it looks like it could be the best-selling drug there's ever been. You need to go back to when we boomers were very young to see why.

In the 1960s, about 45,000 people were being infected with hepatitis C each year - but no one knew it. The first two hepatitis viruses identified were B and A - in the '60s and '70s. Blood transfusions were spreading them. Then 25 years ago - in 1989 - the hepatitis C virus (HCV) was found by scientists at the CDC, NIH, and industry. By then, possibly 380,000 people were being infected each year.

It wasn't till 1992 that the blood supply was cleared of HCV, leading to a big drop in infections. Since then, the people at highest risk of being infected are anyone who ever used a drug intravenously, health care workers, people on hemodialysis, babies born to infected women, and people with HIV. Less than 20,000 people a year get infected now.

Hepatitis C virus and liver fibrosis

Hepatitis C virus can cause liver fibrosis (scarring - depicted here) and cirrhosis (permanent liver injury)

Hepatitis C virus can clear spontaneously without doing any harm. But most people will develop chronic infection. It's hard to know how many will go on to develop serious liver damage, called cirrhosis, though. Estimates range from about 10% within 20 years with some more later, to around 30%. Cirrhosis is life-threatening, with liver transplantation to try to prevent early death. Cirrhosis can also lead to liver cancer.

The number of people in the US with cirrhosis from HCV could peak at 1 million in 2020, with the peak for liver cancer coming later.

The CDC estimates that 3.2 million people in America are infected. CVS estimates that about half have been diagnosed and most have few or no symptoms. The CDC and the US Preventive Services Task Force recommend testing for those who are high risk for getting infected - and everyone born between 1945 and 1965.

Link image to CDC

The CDC's interactive viral hepatitis risk assessment (click on image)

There's no vaccine, and the only way to effectively stop chronic infection progressing is to take drugs. And until recently, that meant a difficult combination - including a weekly injection of pegylated interferon (peginterferon). Some combinations could clear the virus in up to 65-75% of people, and seem to reduce the risk of cirrhosis and liver cancer. But it was a burdensome treatment - for 24 weeks - with a lot of adverse effects.

And many trials of single drugs or the various combinations only studied SVR (sustained virologic response) - viral clearance in the short-term - and not whether treatment reduced cirrhosis or mortality.

Sofosbuvir and other drugs like simeprevir (Olysio) and daclatasvir (Daklenza - which isn't available in the US) can make hepatitis C treatment interferon-free. They're oral - although still used in combination with other drugs, including injections - and the course is half the time. Sofosbuvir combinations have fewer adverse effects and clear up to 90% of infection - even up to 80% in people with cirrhosis.

But the cost for the sofosbuvir alone is around $1,000 a pill - and $84,000 for the course: closer to $95,000 when you count in the drugs used alongside. Forbes reports that is the price set for Harvoni.

Last month, CVS reported that about 10% of people were quitting sofosbuvir treatment without finishing. Restrictions are in place in many parts of the US to contain costs, but more will be needed now. And there's fierce debate about just how far the manufacturer is willing to go to make the drug even close to affordable in less wealthy countries: that company has a dreadful track record on this for HIV drugs. And whether the costs can be carried in rich countries is debatable, too.

Even though billions have been spent on sofosbuvir already, more people were waiting for this next round: the single tablet a day with sofosbuvir/ledipasvir (Harvoni) and other new options. Trials have reported viral clearance well over 90% for Harvoni, with no one quitting during 8 and 12 week courses. But the FDA will have had more data than we've seen yet.

We know the the price of the drugs. It will be years, though, till we understand the full ripple effects.

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The cartoon is my own (Creative Commons License): more at Statistically Funny.

The images of the hepatitis C virus and developing liver fibrosis are from Tarik Asseleh et al, Gene expression and hepatitis C virus infection, Gut 2009, 58(6):846-858.

This post was updated on the day of posting, after the announcement of FDA approval for the ledipasvir/sofosbuvir combination.

* The thoughts Hilda Bastian expresses here at Absolutely Maybe are personal, and do not necessarily reflect the views of the National Institutes of Health or the U.S. Department of Health and Human Services.