News

Posted On: 06/23/2005

Pfizer Begins Production of Novel Heart Drug at Expanded Irish Plant

PharmaManufacturing.com

More than 15 years after Pfizer researchers set out to design a novel medicine that could significantly reduce the risk of heart disease, the company has begun production at a $90 million plant expansion in Ireland.

The facility will manufacture torcetrapib, which Pfizer is combining with Lipitor (atorvastatin calcium) in a new medicine. Torcetrapib was discovered as part of its research efforts to raise HDL, or "good" cholesterol. Researchers believe HDL plays an important role in heart disease.

Pfizer believes torcetrapib/atorvastatin will build on the proven efficacy and safety of Lipitor, the world's most-prescribed medicine to lower LDL, or "bad" cholesterol. Numerous studies with statins have established the critical importance in LDL-lowering for reducing the risk of cardiovascular disease, the world's leading killer of men and women. Pfizer's scientists are testing the hypothesis that simultaneously raising HDL and lowering LDL could provide an even greater reduction in the risk of cardiovascular disease.

The production of the first batch of torcetrapib at Pfizer's Loughbeg, Ireland, facility is the latest in a series of torcetrapib/atorvastatin milestones.

Pfizer has undertaken the largest and most comprehensive clinical trial development program ever. Torcetrapib/atorvastatin's clinical program will involve 25,000 patients at hundreds of medical centers worldwide at a cost of about $800 million.

"If we prove our hypothesis, torcetrapib/atorvastatin has the potential to benefit millions of lives around the world," said Dr. John L. LaMattina, president of Pfizer Global Research and Development. "Nothing is certain except our huge investment. Even if this fails as a new medicine, we will have advanced scientific understanding in this area."

Pfizer researchers began the torcetrapib/atorvastatin program more than 15 years ago, basing their HDL-raising approach on inhibiting CETP, a protein in the liver that transfers cholesterol. In 1990, The New England Journal of Medicine reported that a group of Japanese patients who were lacking the CETP protein had high HDL levels and a low incidence of coronary artery disease.

Pfizer chemists spent years trying to find a compound that could inhibit CETP. Preliminary work led them to their most promising compound -- CP- 529,414, now known as torcetrapib. Other Pfizer researchers then spent several more years improving the compound's physical properties and understanding how torcetrapib worked before it could be administered to people in 1999.

While torcetrapib alone was inadequate in lowering LDL -- with some patients even experiencing slight increases in LDL levels -- consultation with external experts confirmed that the compound should be used with atorvastatin, which has been widely studied and shown to be highly effective at reducing LDL levels.

Pfizer also developed a new dosage form technology called spray-dried dispersion (SDD) in collaboration with Bend Research, which is being used at Loughbeg. The plant in County Cork will use this new technology to manufacture the SDD component that ultimately is combined with Lipitor to formulate the torcetrapib/atorvastatin combination used in the clinical development program.

When the facility expansion is fully operational, it will require 40 employees, said Pfizer Global Manufacturing President Nat Ricciardi. "This is the type of major financial commitment Pfizer is willing to make on an entirely new and yet-to-be-approved medicine because it has potential to improve lives of people around the world," he said. "Having the operation up and running before our regulatory filings should facilitate the review process," Ricciardi said.

In addition to the SDD technology, the Loughbeg facility has the latest in process analytical technology, on-line sensing instruments, and a wide range of novel manufacturing technologies.

An official opening ceremony will be held at the facility on Friday, June 24. The event will be hosted by Nat Ricciardi and Michael Martin, Ireland's minister for enterprise, trade and employment.