Pfizer is to discontinue the global clinical development program for bococizumab—its investigational PCSK9 inhibitor. According to a press release, the totality of clinical information now available for bococizumab—taken together with the evolving treatment and market landscape for lipid-lowering agents—indicates that the drug is not likely to provide value to patients, physicians, or shareholders. As a result, Pfizer has decided to discontinue the development programme, including the two ongoing cardiovascular outcome studies.
With the completion of six bococizumab lipid-lowering studies, Pfizer has observed an emerging clinical profile that includes an unanticipated attenuation of low-density lipoprotein (LDL) cholesterol lowering over time, as well as a higher level of immunogenicity and higher rate of injection-site reactions with bococizumab than shown with the other agents in this class.
The bococizumab SPIRE (Studies of PCSK9 inhibition and the reduction of vascular events) Phase 3 global clinical development programme included six lipid-lowering studies as well as two cardiovascular outcome studies. Pfizer previously announced that four of the lipid-lowering studies met their primary endpoints (SPIRE-SI, SPIRE-AI, SPIRE-HR, SPIRE-FH). Recent top-line results also showed that the two remaining Phase 3 bococizumab 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 cholesterol at 12 weeks compared to placebo among adults with primary hyperlipidaemia or mixed dyslipidaemia at high and very high risk for cardiovascular events who were receiving statin therapy. Bococizumab was generally safe and well tolerated in both trials. An evaluation of cross-reactivity to other PCKS9 inhibitor monoclonal antibodies was not suggestive of clinically important concerns. With this decision to discontinue the bococizumab development program, Pfizer will now halt the two ongoing cardiovascular outcome studies, SPIRE-1 and SPIRE-2.
Paul M Ridker, MD, co-chair executive committee, SPIRE clinical trials programme and director for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, says: “To honour the altruism of trial participants, and to maximise the clinical and scientific knowledge derived from the halted trials, Pfizer has committed to ensuring that the data will be made available to study leaders for independent analysis and prompt public presentation. We believe the available data will allow us to test the core scientific questions posed by the overall program which is in the best interest of patients who volunteered in these clinical trials, and for patients worldwide who suffer from heart disease,”
Bococizumab is a PCSK9 inhibitor that was studied for its potential to lower LDL cholesterol and to improve cardiovascular outcomes. It works by blocking the function of the PCSK9 protein, which interferes with the clearance of LDL-C, a leading known risk factor for heart disease. Bococizumab has not received regulatory approval in any country.