Biotech companies like to talk up the discipline it takes to move a drug through years of development, but discovery sometimes depends on plain serendipity. I got an interesting reminder of that the other day from Barry Quart, the CEO of San Diego-based Ardea Biosciences.
Back in late 2007, Ardea (NASDAQ: RDEA) scientists were looking through some of the data from the company’s lead drug candidate for HIV, including the various blood measurements taken to see if the drug is being metabolized. They found a curious effect. The drug reduced the amount of uric acid in the blood. This is the stuff that can accumulate in the joints of some people, creating intensely painful crystals there, and ugly bumps. It’s the disease known as metabolic arthritis, or gout.
The unexpected finding in the HIV trial sparked the curiosity of Ardea’s scientists and management. Digging into the data, they saw the anti-uric acid activity was caused by a byproduct of the HIV drug, a so-called metabolite. That was important because it showed this wasn’t some kind of clinical trial fluke. Plus, the byproduct also had been safely excreted by more than 150 patients in HIV trials, which meant it would likely be a safe drug. The company got more interested when looking at the business opportunity. About 2.1 million people, mostly over age 40, have gout, according to the National Institutes of Health. Incidence has more than tripled in the past 20 years, as the disease is correlated with being overweight, drinking too much alcohol, or having diets too high in meat or fish. ( Gout was once known as the “Disease of Kings,” thought to afflict leaders like Henry VIII and Benjamin Franklin.)
Then came the best part if you’re a drug developer. Only one new drug for treating gout has been approved by the FDA in the past 40 years, and there was really only one other competitor on the horizon (East Brunswick, NJ-based Savient Pharmaceuticals). It was quite a contrast to the competition Ardea was sizing up for HIV, in which there are already 33 FDA approved drugs setting a high bar for anything new.
“When we first noticed this effect in the HIV trial, I was intrigued, but figured it was probably not going to be of much consequence,” Quart says. “I definitely didn’t see building the company up as a gout company.”
Now he does. Ardea expects to report results from a small pilot study of gout patients this month, Quart says. It ought to be able to move quickly into a Phase II clinical trial of gout patients this year, and then into the final stage of clinical trials in 2010, Quart says. “Unlike a lot of drugs, you can get an answer on this product’s efficacy very quickly,” he says.
Ardea in its current form was started in December 2006. Quart, formerly the president of Napo Pharmaceuticals and an executive vice president of Pfizer’s Global R&D, took over the shell of a dead public company (IntraBiotics). The company had $48.5 million left in cash, and Ardea combined that with about 50 scientific staff and some drug candidates acquired from Valeant Pharmaceuticals, Quart says. The original labs were in Orange County (Costa Mesa, CA), until the company moved to San Diego in March 2008.
Ardea’s gout drug got its start, as mentioned earlier, as a metabolite shed off of its other HIV drug, RDEA806, when that drug gets broken down in the body. Once Ardea figured out that the metabolite was responsible, it made a more potent formulation into a drug called RDEA594. An initial Phase I trial in healthy volunteers showed that the new formulation is much more potent than RDEA806 in its ability to lower uric acid, and the effect is comparable to benzbromarone, another gout drug, which was withdrawn from the market in 2003 by Paris-based Sanofi-Aventis for liver toxicity.
The Ardea drug is thought to work by blocking the ability of kidneys to re-absorb too much uric acid, a different way of working than the standard drug allopurinol, which has been around for decades, Quart says. That means Ardea’s compound and allopurinol ought to be able to work in combination, he says.
Ardea’s candidate has the potential to be given as a once-daily pill to keep patients’ uric acid levels low and to keep patients from getting crystal buildup in joints that can lead to painful flare-ups. FDA approval would likely require a trial in which Ardea shows it can lower uric acid and keep it down at least six months, he says.
One potential snag is that some gout patients on the drug might feel more pain on the Ardea drug before they start feeling better. As their uric acid come down aggressively, the disfiguring bumps in joints, known as tophi, can break down, creating a painful inflammatory response, Quart says. For the first few months on the Ardea drug, until those bumps go away, patients might need to take a combination drug to suppress the inflammation, he says.
These trials don’t look like they will be massive undertakings that will require finding a big pharma partner, so Ardea intends to hold onto 100 percent ownership of the gout drug at least through the final phase of clinical trials, Quart says. There are other biotech companies in early stages of development that also are eyeing gout, including Regeneron Pharmaceuticals. But Quart likes the fact that others seem focused on the inflammatory response to gout, and not the uric acid buildup that his company is tackling. He sounds confident that Ardea can hold its own against whatever comes down the pipeline in the next few years.
“Gout is in a Renaissance,” Quart says. “There’s clearly an unmet medical need. Patients are looking for new therapies.”