Pfizer, which has struggled to find a follow-up to its blockbuster anticholesterol drug Lipitor, has stopped work on bococizumab, a cholesterol-lowering agent in Phase III clinical trials. The firm cites efficacy and safety concerns as well as a “market landscape” unfavorable to new drugs in the category.
The company says its earnings will be clipped by 4 cents per share, or about $300 million, following the decision to discontinue trials of the drug, an antibody-based PCSK9 inhibitor.
Bococizumab’s demise marks Pfizer’s second misfire in producing a cholesterol drug to succeed Lipitor, which lost patent exclusivity in 2012. Pfizer pulled the drug candidate it hoped would follow on immediately, torcetrapib, in 2006 after an increase in deaths in patients taking it along with Lipitor in clinical trials. Pfizer began work on bococizumab at about the same time.
Drugs in the PCSK9 class work by blocking the cholesterol regulator proprotein convertase subtilisin/kexin type 9. They can reduce levels of low-density lipoprotein cholesterol (LDL), sometimes called “bad” cholesterol, by as much as 60%.
Pfizer’s bococizumab tests, however, showed that the drug’s cholesterol-lowering capacity declines over time. The tests also uncovered higher levels of immunogenicity and injection-site reactions than occur with other drugs in the class.
The company’s decision was also influenced by the difficulty that PCSK9 drugs already on the market—Amgen’s Repatha and Sanofi and Regeneron’s Praluent—have met as insurers direct patients to lower-priced statins available as generics, such as Lipitor. Both brand-name PCSK9 inhibitors carry a list price of about $14,000 a year.
John LaMattina, a senior partner at PureTech Ventures and former head of R&D at Pfizer, says Pfizer’s decision comes as many of the firm’s peers are stepping back from cholesterol drug research.
“Because current therapies for cardiovascular disease are pretty good,” he says, “distinguishing a new agent so that you can justify payers reimbursing it, and doctors prescribing it, requires you to do a lot of work preparing a new drug application.”
Pfizer, he notes, reported 94 ongoing research programs in its third-quarter earnings report last week, of which 39 are in oncology, 10 in rare disease, and seven in cardiovascular disease.