If this all feels like déjà vu, recall that the original Esperion was a spin-out, too—from Warner-Lambert in 1998. It was founded by Lipitor (atorvastatin calcium) codiscoverer Roger Newton, after his ideas for using synthetic high-density lipoprotein (HDL) derivatives as biopharmaceuticals were rejected by company management. Warner-Lambert pursued small-molecule cardiovascular therapies instead, while Esperion 1.0 moved forward with HDL derivatives for acute atherosclerosis and began to build a portfolio of biologics and small molecules to address chronic cardiovascular disease by elevating HDL through the reverse lipid transport pathway.
When Pfizer, of New York, bought Warner-Lambert in 2000, however, the pharmaceutical company's attitude to HDL and reverse lipid transport did a turnabout. Pfizer opened its wallet for Esperion, with a view to using Esperion's lead HDL drug candidate, ETC 216 (phospholipid/recombinant apolipoprotein A-I (Apo A-I) Milano), as a potential adjunct for Lipitor and its lead small-molecule therapy, torcetrapib, which at the time was in late-stage trials and thought to be nearing commercialization. The Esperion purchase also brought on board a 22-amino acid peptidomimetic of Apo A-I (ETC 642), a large unilamellar vesicle comprising egg phosphatidylcholine (ETC 588), and two small-molecule plasma-lipid regulating agents (ETC 1001 and ETC 1002) designed to regulate triglycerides and cholesterol. Interest centered on ETC 216, though, which had performed well in a clinical study at the Cleveland Clinic under Steve Nissen (JAMA 290, 2292–2300, 2003), showing regression of atherosclerosis after five infusions one week apart. That helped create a buzz around Apo A-I Milano and Esperion. Thus, when Pfizer decided to buy, the $1.3 billion price tag was a 54% premium over the preceding 20-day average stock price.
This is a preview of subscription content, access via your institution