National Editor

The winter solstice, once celebrated for its promise of steadily longer days, brought sunny news for Esperion Therapeutics Inc. this year in the form of a $1.3 billion buyout by Pfizer Inc. - at $35 per share, a 54 percent premium to the company's average closing share price during the previous 20 days.

"We thought it would be much better to link up with the global leader in cardiovascular medicines than go it alone," said Roger Newton, president and CEO of Ann Arbor, Mich.-based Esperion, which has two Phase II drug candidates.

Wall Street agreed. Esperion's stock (NASDAQ:ESPR) soared more than 52 percent on the news, closing Monday at $34.52, up $11.82.

New York-based Pfizer said it will commence a cash tender offer to acquire the shares of Esperion stock, thereby gaining the firm's technology for raising high-density lipoprotein (HDL), the "good cholesterol."

The deal is expected to close at the end of next year's first quarter, and Esperion will operate as a division of the Pfizer Global Research and Development organization, remaining in Ann Arbor.

Recently finishing a Phase II trial was Esperion's lead product, ETC-216 (ApoA-I Milano/phospholipid complex, also known as AIM), a variant of ApolipoproteinA-I (ApoA-I), which is the major protein component of HDL.

ApoA-I Milano is prevalent in a small population of northern Italians with paradoxically low levels of HDL cholesterol. Though that normally would correlate with high risk for cardiovascular disease, carriers of the ApoA-I Milano gene show a reduced risk, an effect believed to be due to enhanced reverse lipid transport (RLT), which is the body's process of removing excess cholesterol and other lipids and transporting them to the liver for elimination.

ETC-216 is the human recombinant version of ApoA-I Milano combined with a phospholipid to form a complex that imitates the structure and function of HDL, therefore intended to mimic HDL's beneficial properties and enhance RLT.

Last month, the Journal of the American Medical Association published results from the 47-patient Phase II trial. (See BioWorld Today, Nov. 6, 2003.)

The drug looks like a near-perfect fit with Pfizer's marketed product Lipitor (atorvastatin calcium), which is the world's most prescribed agent for reducing low-density lipoprotein (LDL), the "bad cholesterol." And Esperion - founded by the scientists who helped discover and develop Lipitor - looks like a perfect fit with Pfizer.

Pfizer also is developing as a regularly dosed oral drug Lipitor in combination with torcetrapib, an agent that inhibits the action of cholesterol ester transfer protein. Phase II data have shown the pair enhances the LDL-lowering effect of Lipitor while boosting HDL. Esperion's drugs are to be used intravenously in a hospital setting.

"We look at this as a complementary therapy," Newton said. "Initially, the biopharmaceuticals we're developing and that are in the clinic would be used in combination with existing treatments for [acute coronary syndrome] standard of care. Our feeling is that this therapy focuses on attacking the disease at its source, the arterial wall."

Before leaving the hospital, the patient would get an infusion of Esperion's drug and "come back weekly for four to eight infusions, which take no more than half an hour," he said.

Because of an intellectual property agreement between Esperion and Peapack, N.J.-based Pharmacia Corp., Pfizer had right of first refusal to market ETC-216. Pfizer and Pharmacia merged in a $60 billion deal disclosed in the summer of 2002.

Esperion also has in Phase II trials ETC-588, a liposome said to act as a cholesterol sponge. Data from a Phase II study with acute coronary syndrome patients are expected in the first half of next year.

A third compound in the clinic, ETC-642, has completed two Phase I trials in patients with stable atherosclerosis. Like ETC-216, the drug is a protein/phospholipid complex that mimics HDL. Another Phase I trial is under way, with data expected in the first quarter of next year.

ETC-1001 (formerly known as ESP-31015) is Esperion's oral small-molecule drug for boosting HDL and reducing triglycerides as well as LDL. A Phase I dose-finding trial is complete, with a Phase I multidose trial expected in the first half of next year.

The lipid-lowering market is estimated at about $20 billion, and Esperion now has a much better chance of taking a share with one or more of its HDL-focused drugs, Newton said.

"That's been our mission all along," he said, noting that Esperion explored several options with Pfizer: "a single-product partnership, a more strategic alliance, and the one that trumps all of those - the [merger or acquisition] offer. Certainly our board lived up to its responsibility to shareholders."

Lehman Brothers in New York and Morgan, Lewis & Bockius in Philadelphia advised Esperion in the transaction. Counsel for Pfizer was Lazard, of New York, and Cadwalader, Wickersham & Taft, also of New York.