Thoughtleader: Rob Scott, AtheroGenics

With "launched the world's best-selling drug" on his resume, Rob Scott was ready for his next professional endeavour. The former Pfizer executive is now head of R&D and chief medical officer at AtheroGenics, named for the signature technology that's being used to develop AGI-1067, a cardiovascular anti-inflammatory in late Phase III clinical trials.

Rob Scott, MD

Scott still gets his Big Pharma fix—AtheroGenics partnered in December 2005 with AstraZeneca to commercialize AG-1067—but the South Africa native feels right at home working for a smaller operation—on a bigtime project.

Pharm Exec: When did you first know that Lipitor was going to be successful?

Rob Scott: We used to hold these R&D days at Pfizer, when we'd talk about where we should be going, which drugs we should be trying to develop, which approaches we should be trying to follow. About a year before we did the deal [Pfizer acquired Parke-Davis, developer of Lipitor, when it bought Warner-Lambert in 2000], we were reviewing a bunch of approaches that Pfizer had. And every time we looked at an approach, people would say, "Well, that's not going to work out so well if Lipitor makes it to the market." And then somebody in the room said, "Well, we should try and get Lipitor, then."

We were going to be launching against other companies with deep pockets, that had outcomes data for their statins. So we were realistic at the time, but I think that both Merck and BMS missed the opportunity to blunt the launch of Lipitor.

Compare that with where you sit today, with the drug you have in development.

Lipitor was going to be the fifth statin on the market. In some respects, that makes life easier, because you know the approach is going to work, and that there's a high degree of acceptance in the marketplace. But we didn't have anything really exciting to talk about. We could say that we lowered LDL more than the competitors, but that's not really sexy.

AGI-1067 is a brand-new approach. There are no other drugs in this class. When we launch, we're going to have to persuade people—make them understand how the drug works.

How was 1067 born?

Back in about 1992, the two scientific co-founders of AtheroGenics, Wayne Alexander and Russ Medford [current CEO], came up with a very novel concept. The first thing they said is that atherosclerosis is mainly an inflammatory disease. That was something people were starting to talk about, but it wasn't widely accepted.

[The founders] said that there are certain intracellular mechanisms that turn on the inflammation, and that these mechanisms can be blocked with an antioxidant—that was the basic technology. AtheroGenics was formed out of that idea.

The way 1067 works is that it's absorbed into cells, and it blocks a message that comes from outside the cell to the nucleus that tells the cell to turn on various inflammatory processes. What gets this message going are all of the current risk factors. So if you have hypertension, high blood pressure, high glucose with diabetes, high lipids, if you smoke, have a bad diet and lifestyle—all of those things turn on this oxidant signaling that tells a cell to go into the more inflammatory state. 1067 acts on that signaling. Instead of focusing on individual risk factors, we're trying to block the next step down from that.

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.

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 1067.

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 drug.

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.

Do you work long hours?

Everybody here is working themselves almost to death. We have a very small team. It's not Big Pharma. We can all see each other's offices. We don't send e-mails to each other when we need to talk. We just walk down there and talk to the person. There's tremendous focus here and people are really excited.

What has it been like to switch from a huge company like Pfizer to a small company in Atlanta?

It wasn't as much culture shock as you might think. I worked for Pfizer in South Africa, which was a small company—about 200 people. So I understand the small-company culture. In a way, it was a bit like coming home.

Rob Scott, MD is executive vice president of R&D and chief medical officer for AtheroGenics. He's been with the company since 2002, when he was hired from Pfizer. Most recently as head of the cardiovascular and metabolic group, Scott was with Pfizer for 10 years. During that time, he handled global development for such products as Lipitor, Norvasc, and Exubera, and served as medical director of Pfizer's laboratories in South Africa, his home country.