March 5 (Bloomberg) -- Resverlogix Corp., without a marketed product, may accomplish what Pfizer Inc., the world’s biggest drugmaker, couldn’t: Creating a new medicine that fights heart disease by raising so-called good cholesterol.

If the treatment, dubbed RVX-208, shows it can reverse the build-up of artery-clogging plaque, it may grab a “substantial” portion of the $35 billion cholesterol-fighting market, said Simos Simeonidis, an analyst with Rodman & Renshaw Inc. in New York. Resverlogix is in “detailed discussions” with several companies seeking to partner or license the drug, said Chief Executive Officer Donald McCaffrey, 51, in an interview. He declined to identify the potential partners.

New York-based Pfizer spent more than $2 billion on two similar treatments without success. The drugs were tested by Steven Nissen, 61, the Cleveland Clinic cardiology chief who is leading the Resverlogix trials. Nissen said RVX-208 works differently than the Pfizer drugs, switching on a protein that helps spur the production of HDL, or good cholesterol.

“There is definitely a lot of interest from big pharma” in Resverlogix’s drug candidate, said Simeonidis. “If this drug works, it could be as big as Lipitor.” Pfizer’s Lipitor, the world’s best-selling drug, generated $11.4 billion in revenue last year, according to data compiled by Bloomberg.

Pfizer, Merck & Co. of Whitehouse Station, New Jersey, and Swiss drugmakers Novartis AG and Roche Holding AG “would potentially be interested” in co-developing RVX-208, Simeonidis said. He doesn’t have any specific knowledge of the companies’ interest, and all four declined to comment.

Rising Shares

Resverlogix rose C$1.52, or 34 percent, to C$6.02 at 4:00 p.m. in Toronto Stock Exchange trading, after earlier touching C$7.37. The shares have more than doubled this year. The company, which has a market value of about C$237 million ($230 million), has no revenue.

“What would make a good fit is a pharmaceutical company that has a strong cardiovascular position and an established sales network,” said McCaffrey, who co-founded the nine-year- old, Calgary-based drug developer.

Prospective partners “may want to wait to see more data,” said analyst Simeonidis. “Then again, there’s such a huge potential they may be willing to take a flyer.”

Best-selling heart drugs Lipitor and London-based AstraZeneca Plc’s Crestor lower production of so-called bad cholesterol, or LDL, by blocking an enzyme in the liver. These drugs belong to a class of medicines known as statins.

New Approach

Resverlogix’s product would increase the levels of a protein called ApoA-1 that helps produce HDL, which removes bad cholesterol from arterial plaque and ferries it to the liver where it can be disposed. People with naturally high levels of HDL are less likely to develop heart attacks or die from cardiovascular disease, studies show.

Resverlogix is banking that artificially raising HDL will have the same effect.

Only one treatment now commercially available is marketed to increase good cholesterol. Niacin, a B vitamin, elevates HDL “but it’s not clear whether it lowers cardiac events,” according to Stephen Kopecky, a cardiologist at the Mayo Clinic in Rochester, Minnesota.

High doses of niacin are available in prescription form. Abbott Laboratories, based in Abbott Park, Illinois, makes Niaspan, the top-selling non-generic form of niacin. The drug generated $990 million in U.S. sales last year, according to Norwalk, Connecticut-based research firm IMS Health Inc.

Facial Flushing

Use of Niaspan has been limited because it can cause elevated blood sugar and facial flushing. In a 2009 study, one- third of patients newly treated with niacin reported severe to extreme flushing.

Heart disease is the leading cause of mortality in the U.S., resulting in 632,000 deaths a year, according to the Centers for Disease Control and Prevention in Atlanta. In coronary artery disease, fat, cholesterol, calcium and other substances -- collectively known as plaque -- build up in the blood vessels that supply oxygen to the heart, a condition that can lead to a heart attack.

A new class of medicines for combating the disease is “overdue,” according to the Cleveland Clinic’s Nissen, who said he doesn’t own Resverlogix stock and isn’t being paid for his RVX-208 research. Statins only reduce the risk of heart attack and stroke by 25 to 35 percent, he said.

Water Supply

“We could put statins in the water supply and heart disease would still be the leading cause of death in the developed world,” Nissen said in a telephone interview.

Over the past decade, Nissen tested both of the experimental HDL medicines that passed through Pfizer’s pipeline.

Pfizer acquired ApoA-1 Milano, a naturally occurring variant of the protein, through its $1.3 billion acquisition of Esperion Therapeutics Inc. in 2004.

Once hailed as “Drano for the heart,” ApoA-1 Milano showed a reduction of plaque in early testing, according to a Nissen- written report published in the November 2003 issue of the Journal of the American Medical Association. The protein, mined from bacteria, turned out to be too difficult to produce.

After conducting “extensive research into the large-scale manufacturing of ApoA-1 Milano,” Pfizer decided “to focus on other drug candidates in its portfolio,” company spokeswoman Anne Wilson said in an e-mail. The drugmaker sold the compound to Parsippany, New Jersey-based Medicines Company in December for $10 million and milestone payments if advances are made.

Commercial Potential

Nikhil Mehta, the director of cardiovascular portfolio at Decision Resources, a biopharmaceutical research firm based in Waltham, Massachusetts, said the commercial potential of RVX-208 is “much greater” than the failed Pfizer drug.

“One of the main attractions of Resverlogix’s drug is that it is oral, unlike Milano, which was given as an infusion,” he said in a telephone interview.

Pfizer also spent $1 billion attempting to develop the compound torcetrapib, a type of experimental medicine called a CETP inhibitor. CETP inhibitors aim to raise good cholesterol levels by blocking an enzyme that metabolizes HDL.

The company at one point projected $13 billion in annual sales for torcetrapib as the successor to Lipitor, which faces generic competition in 2011. Development of the drug was halted in December 2006 when a study found that deaths among those on the medicine were 60 percent higher than among people who didn’t get it.

Market Value Plunges

Pfizer shares fell 11 percent on the first trading day after the announcement, wiping out $21 billion in market value, and the drugmaker later dropped most of its early heart-disease research.

“Nissen kind of got burned” on torcetrapib, said the Mayo Clinic’s Kopecky. “He was sure the CETP inhibitors were going to be great. Torcetrapib wasn’t, and it blew his hypothesis of saying, ‘I know what’s going to work and what’s not going to work.’”

An early trial of RVX-208, concluded in August, met primary endpoints by safely increasing ApoA-1 levels by 5 to 10 percent in all 72 participants, Resverlogix said. The company finished enrolling patients in the next phase of testing on Feb. 8.

In this study, about 280 patients with coronary artery disease will be dosed with Resverlogix’s experimental drug for 13 weeks to see how it affects their cholesterol levels. The company may present data from the study at the American Heart Association meeting in Chicago in November, CEO McCaffrey said.

The company also is conducting a second mid-stage study involving 120 patients who suffered a heart attack in the four weeks before the trial began. The study will use ultrasound to measure plaque volume.

Resverlogix obtained $30 million in financing in the past year, enough cash to pay for the current trials, McCaffrey said.

If these studies are successful, Resverlogix plans to start the third and final round of testing needed for regulatory approval in mid-2011, McCaffrey said. Assuming all goes well, the company plans to file for approval with the U.S. Food and Drug Administration in 2015, he said.

“Hope springs eternal,” Nissen said. “We need to keep trying to find an HDL-raising strategy that works.”

To contact the reporters on this story: Ellen Gibson in New York at egibson9@bloomberg.net;