Pfizer has discontinued the clinical development program for bococizumab, its investigational proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor. In its announcement, the company said that “the totality of clinical information now available for bococizumab, taken together with the evolving treatment and market landscape for lipid-lowering agents, indicates that bococizumab is not likely to provide value to patients, physicians, or shareholders.” As a result, Pfizer decided to halt the development program, including two ongoing cardiovascular outcome studies (SPIRE-1 and SPIRE-2).
Bococizumab was studied for its potential to lower low-density lipoprotein-cholesterol (LDL-C) and to improve cardiovascular outcomes. The drug is believed to work by blocking the function of the PCSK9 protein, which interferes with the clearance of LDL-C, a leading risk factor for heart disease. Bococizumab has not received regulatory approval in any country.
With the completion of six lipid-lowering studies of bococizumab, Pfizer observed an emerging clinical profile that included an unanticipated attenuation of LDL-C lowering over time, as well as a higher level of immunogenicity and a higher rate of injection-site reactions with bococizumab than with other agents in that class.
The phase 3 SPIRE (Studies of PCSK9 Inhibition and the Reduction of Vascular Events) clinical development program for bococizumab included the six lipid-lowering studies as well as two cardiovascular-outcome studies. Pfizer previously announced that four of the lipid-lowering trials (SPIRE-SI, SPIRE-AI, SPIRE-HR, and SPIRE-FH) met their primary endpoints. Recent top-line results also showed that the two remaining lipid-lowering trials, SPIRE-LDL (Low-Density Lipoproteins) and SPIRE-LL (Lipid Lowering), met their primary endpoints, demonstrating a significant reduction in the percent change from baseline in LDL-C at 12 weeks compared with placebo in adults with primary hyperlipidemia or mixed dyslipidemia at high or very high risk for cardiovascular events who were receiving statin therapy. Bococizumab was generally safe and well tolerated in both studies.
Source: Pfizer; November 1, 2016.