Global development of investigational PCSK9 Inhibitor discontinued
01/11/2016
Clinical studies evaluating the third PCSK9 antibody, bococizumab, will be halted, due to an attenuation of LDL-c lowering over time and higher immunogenicity and more injection site reactions.
SourceNews - Nov. 1, 2016
The global clinical development program for bococizumab, an investigational Proprotein Convertase Subtilisin Kexin type 9 inhibitor (PCSK9i), will be discontinued. 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, the company Pfizer has decided to discontinue the development program, including the two ongoing cardiovascular outcome studies.
With the completion of six bococizumab lipid-lowering studies, a clinical profile emerges that includes an unanticipated attenuation of LDL-C 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 goal of treating elevated cholesterol is to reduce the occurrence of cardiovascular events such as heart attacks and stroke, which requires long-term effective and durable cholesterol-lowering.
Pfizer is working to ensure that all regulatory authorities are informed, and that all trial investigators are informed and instructed on next steps. If patients have questions, they should speak with their study physician for more information.
“To honor the altruism of trial participants, and to maximize 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,” stated Paul M. Ridker, MD, Co-chair Executive Committee, SPIRE clinical trials program and director for Cardiovascular Disease Prevention, Brigham and Women’s Hospital.
The bococizumab SPIRE (Studies of PCSK9 Inhibition and the Reduction of vascular Events) Phase 3 global clinical development program included six lipid-lowering studies as well as two cardiovascular outcome studies. Four of the lipid-lowering studies met their primary endpoints (SPIRE-SI, SPIRE-AI, SPIRE-HR, SPIRE-FH). Recent top-line results also showed 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 from baseline in LDL-C 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 PCKS9i 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.
Press release Pfizer November 1, 2016
With the completion of six bococizumab lipid-lowering studies, a clinical profile emerges that includes an unanticipated attenuation of LDL-C 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 goal of treating elevated cholesterol is to reduce the occurrence of cardiovascular events such as heart attacks and stroke, which requires long-term effective and durable cholesterol-lowering.
Pfizer is working to ensure that all regulatory authorities are informed, and that all trial investigators are informed and instructed on next steps. If patients have questions, they should speak with their study physician for more information.
“To honor the altruism of trial participants, and to maximize 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,” stated Paul M. Ridker, MD, Co-chair Executive Committee, SPIRE clinical trials program and director for Cardiovascular Disease Prevention, Brigham and Women’s Hospital.
The bococizumab SPIRE (Studies of PCSK9 Inhibition and the Reduction of vascular Events) Phase 3 global clinical development program included six lipid-lowering studies as well as two cardiovascular outcome studies. Four of the lipid-lowering studies met their primary endpoints (SPIRE-SI, SPIRE-AI, SPIRE-HR, SPIRE-FH). Recent top-line results also showed 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 from baseline in LDL-C 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 PCKS9i 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.
Press release Pfizer November 1, 2016