How does this relate to metabolic syndrome?
Metabolic syndrome is when patients have a variety of increased risk factors. They have increased blood pressure, bad lipids,
insulin resistance. And all of those things turn on this oxidant signaling within the cell and tell it to go to a more inflammatory
state. We're trying to block the integrated signal from all of those risk factors. We think 1067 will have particular application
in patients with metabolic syndrome or patients with multiple risk factors.
PPARs [peroxisome proliferators activator receptors] are also known to be effective against metabolic syndrome, but have a
mixed safety record. How are you addressing the safety issue in developing 1067?
PPARs play a very prominent role in the treatment of diabetes. But clearly they're not the answer for everybody. We still
need another approach—something that's more directly targeted to inflammation.
When I joined AtheroGenics about four years ago, we had some general thoughts about safety. We had treated maybe 500, 600
patients. We knew that there weren't any overwhelming safety concerns. Now we've treated about 7,000 patients. We've got our
pivotal Phase III study that has been running for almost three years with 6,127 subjects. And we've had about four DSMB meetings.
We know that 1067 is safe.
What persuaded you to use outcome studies?
We had a really practical problem: This is a new class of drugs targeted directly at the artery wall. There's nothing that
we can measure easily, like blood pressure or cholesterol, to show that the drug works and to get it approved. In order to
demonstrate that this drug is of value, we've had to jump over the easy stuff and go straight to the stuff that people really
care about: Will this drug improve long-term outcomes? Will it reduce important clinical events?
With statins, there was a lot of epidemiological evidence that they would lower cholesterol and LDL—and then they had to demonstrate
subsequently that they really did improve events. In the case of 1067, we didn't have that evidence.
This really is a problem for emerging pharma or biotech companies like ourselves. The barrier to entry in cardiovascular disease
is extremely high. One study can cost you $100 million. It's very hard for a small company to come up with the funding for
That's one of the challenges. What opportunities exist when you're bringing to market a new drug?
People sometimes think that because we have the statins, the problem is dealt with. The reality is that as good as statins
are, they only reduce about one third of the event. So of every 100 patients who are going to have a major event or die, only
30 of those patients will benefit from a statin. Seventy percent of the problem is still there.
Nearly 20 years since the launch of statins, cardiovascular disease remains the single-largest cause of death in the United
States. It kills more people than all forms of cancer combined. And a statement coming out of the UN Millennium Development
goals is that cardiovascular disease is the commonest cause of death in the developing world as well.
The problem isn't beaten. We took a bite out of it, but we need another class of drugs. It's a very exciting opportunity for
Most drugs coming out of the pipeline today target small markets. Is that what you're doing with 1067?
Big Pharma is moving away from the blockbuster model. Their productivity in that regard has been abysmal in recent years.
But 1067 will fall into the category of blockbuster drugs. If our pivotal Phase III study is positive, this will be a blockbuster
Does being from Zimbabwe affect your professional goals?
I'd like to think that countries like Africa will have access to our drugs. This is a problem that payers and pharmaceutical
executives are going to have to try and address going forward. And I can't profess to have any answers to that. But yes, I'd
like to see these therapies make it globally, rather than just into focus markets.