Just three years ago patients suffering from hepatitis C faced some bleak treatment options. The main drug employed against this viral disease was only available via injection. It also came with serious side effects and—for too many patients—was not even effective. Then a transformative new pill called sofosbuvir hit the market.
Better known as Sovaldi, the drug managed to recast hepatitis C from a hard-to-treat illness into an easily managed one that can be cured in just a few months. When used alongside other drugs it also worked much faster than any other hepatitis C treatments and had both fewer side effects and much higher success rates. About 90 percent of patients with a common form of the virus are cured with the medicine. The catch, of course, has been the price tag: more than $80,000 for a course of treatment.
Even before it went on sale the treatment became a flashpoint that pitted patients against pharmaceutical companies over the cost of medical innovation, and the debate cast a pall over the drug’s release. But the medical feat—creating this unprecedented weapon against hepatitis C—has scooped up accolades including the announcement Tuesday that its creator, Michael Sofia, has netted a prestigious Lasker Award for revolutionizing hepatitis C care. Lasker Awards, which recognize scientists’ major contributions to medical science or those who have performed public service on behalf of the field, are often considered a pit stop on the way to a Nobel Prize.
Sofia, who devised the drug while working at the pharmaceutical company Pharmasset, shares this award with two other scientists who did fundamental work on the disease: Ralf Bartenschlager at Heidelberg University and Charles Rice at The Rockefeller University. The two scientists managed to coax viral cells that cause hepatitis C to multiply inside lab-grown host cells, enabling crucial testing required to invent candidate drugs. Other 2016 Lasker awards will go to a scientist who unraveled the mechanism by which cells copy DNA and to a trio of researchers who identified how humans and most animals sense and adapt to changes in oxygen availability.
Scientific American spoke with Sofia, who now conducts research at Arbutus Biopharma, in a wide-ranging conversation about drug pricing issues, challenges in the field and being comfortable with failure.
[An edited transcript of the interview follows.]
The drug sofosbuvir [brand name Sovaldi] is named in your honor. What it’s like to have a drug named after you?
It is certainly a bit humbling. It’s a bit awkward in many ways. I frequently get the question about it, so the word is out there. Along the way there were other options that the team at my company, Pharmasett, were considering, but the preference was to at least recognize the key inventors and the person who was responsible for leading the project.
Did your upbringing in Baltimore influence your future interests in any way?
Actually, not really. I come from a very modest background. No one in my family at the time had any connection to science or medicine. My father was a barber and my mother was a payroll clerk. They had very little education. But my interest in science actually was there from a very early age. I remember being drawn to stories about real-life people. I would pick up these books at the library about some of the great scientists of days past like Newton and Galileo and would just be captivated by the whole concept of discovery and new knowledge and discovering new things. My family did not have very much money, so every Christmas I would get to choose one thing. One year I got a telescope, one year a microscope and one year a chemistry set. It continued to sort of develop from there. I remember winning the science fair in grade school. My project was “how radar works.” I then went on to attend a math–science–engineering magnet school in Baltimore, which was kind of unusual at the time—this was the mid-1970s. And my interest in math and science grew from there.
Many people in the U.S. with hepatitis C are poor, and several hundred thousand are incarcerated. Whose responsibility is it to make treatment affordable?
[long pause] This is a pretty controversial area. As a scientist I tend to focus my energies and efforts in trying to identify drugs that will stop or change the course of disease. I don’t get into a lot of these issues about pricing and so forth.
In curing this disease there are many, many downstream costs that are now eliminated because hepatitis C not only leads to severe liver damage and potential liver cancer—and is the cause of many, many liver transplants that exist in the U.S. and throughout the world—but also having hepatitis C leads to many other comorbidities like neurological problems and other issues caused by hepatitis C. So if you clear the virus, you eliminate these other problems and these patients can return to a pretty normal life after [treatment]. Getting access to the drug will really reap the benefit both from an economic standpoint and also from a burden on the health care system standpoint.
Obviously there are now more debates about other high-priced drugs or therapies including, most recently, EpiPens. How can these prices be reined in?
I’ve never been involved in pricing decisions. There are many things that contribute to the actual cost a patient pays. The cost of a drug comes not only from a manufacturer. There is a middleman—the retail provider and so forth and so on who work independently and want an independent profit. How do you give someone who is willing to invest in drug discovery a return on their investment versus putting their money somewhere else where they could return a better return on their investment? It’s a difficult problem. I don’t know what the solution is. It’s certainly not a solution that I have or I can provide but it’s something I think over time, with all the players involved in this system, that they will have to work together in some way to address.
From a drug research standpoint, what is particularly challenging when it comes to hepatitis C as opposed to hepatitis B or hepatitis A [both of which have vaccines available]?
Each of these viruses have their own unique challenges. I’m working on trying to identify a cure for hepatitis B right now. It is a very different virus than hepatitis C. So, for example, hepatitis B is a DNA virus that has a viral reservoir. Hepatitis C is an RNA virus without a viral reservoir. One of the big challenges for hepatitis C is that there are a number of different forms of it, called genotypes. There are six different genotypes. They are different from each other, although in some ways they are the same. Hepatitis C also has a high rate of viral replication, so it makes lots of new virus every day at a high rate and it doesn’t have a good way of proofreading its genome as it replicates, so it is always making errors. The fact that those errors happen mean many subtypes of the virus are formed, and also that the virus can become resistant to the drug because it changes so quickly. Some challenges were to attack and inhibit all the different forms of the virus and have high barrier resistance—meaning even if the virus mutated the drug would still be active against it.
Are there any lessons from your hepatitis C work that are directly applicable to hepatitis B?
I think one of the things is the use of combination therapy. What we learned in hepatitis C world and also from HIV is that combinations of drugs with different mechanisms of action would have the maximum benefit.
What does winning this award do, if anything, to help with your work?
It heightens the awareness of the kind of work we do and the suffering of the patients. Hepatitis is not like HIV where everyone knows about it. It’s not like cancer where everyone knows someone who has had cancer and they understand the severity of the disease. For the field of viral hepatitis, although its burden is absolutely huge—170 million individuals worldwide for hepatitis C and 350 [million] to 400 million are infected chronically with hepatitis B—these are diseases that progress over a long period of time. They are what you could call silent killers, and they aren’t on the radar screen. The award will increase awareness about these diseases, their importance and their debilitating nature.
I read in The New Yorker that you said Sovaldi was remarkable because “It does exactly what we designed it to do, which is one of those things that hardly ever happens.” Why is that?
What you do in the laboratory does not really translate into a human clinical setting. All the cell-based models and animal models and in vitro systems that you have at your disposal in a lab setting are simply models of the disease and how the human body works. So we designed this molecule and tested it as much as we could preclinically and tried to design into the molecules all the features we wanted. But it wasn’t until we got it into a human being that [we saw that] all steps that needed to happen actually happened as we hoped.
Finally, what advice might you give to young scientists today or those considering a career in science?
When I started my first undergrad research in a real lab at Cornell, I was working for a senior grad student, and he says to me “Mike, you know, I want to tell you this first: Eighty percent of what you do will fail. Twenty percent of what you do will succeed in research. If you are not happy with that 20 percent success rate, you don’t belong here.” It stuck with me forever because science is an endeavor where there is a tremendous amount of failure along the way. But the successes—especially in the field of medical research—are tremendously gratifying. You really do have the ability to impact people’s lives throughout the world, and there are very few endeavors I think that will afford you that opportunity.