Date: 2016-11-01
Type of
information: discontinuation of development
phase: 3
Announcement: discontinuation of development
Company: Pfizer (USA - NY)
Product: bococizumab
Action
mechanism:
- monoclonal antibody/PCSK9 inhibitor. Bococizumab is an investigational PCSK9i being studied for its potential to lower LDL cholesterol. It works by blocking the function of the PCSK9 protein, which interferes with the clearance of LDL cholesterol.
Disease: hyperlipidemia
Therapeutic
area: Cardiovascular diseases - Metabolic diseases
Country: Australia, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Denmark, Finland, France, Germany, Hungary, India, Ireland, Israel, Italy, Republic of Korea, Mexico, The Netherlands, New Zealand, Poland, Puerto Rico, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, UK, USA
Trial
details:
- SPIRE (Studies of PCSK9 Inhibition and the Reduction of vascular Events) is an extensive research program to study bococizumab. The SPIRE Phase 3 global clinical development program involves approximately 32,000 patients and consists of six lipid-lowering studies (SPIRE-SI, SPIRE-AI, SPIRE-HR, SPIRE-FH, SPIRE-LL and SPIRE-LDL) as well as two cardiovascular outcomes studies (SPIRE-1 and SPIRE-2).
- The Phase 3 SPIRE-AI study – a 12-week, double-blind, placebo-controlled, randomized, parallel-group, multicenter, clinical trial in 299 patients with hyperlipidemia or mixed dyslipidemia receiving statin therapy and whose LDL-C ?70 mg/dL – assessed the efficacy, safety, tolerability and subcutaneous administration of bococizumab 150mg and 75mg with a pre-filled pen. Co-primary endpoints included the percent change from baseline in fasting LDL-C at week 12 and the delivery system success rate, defined as the percent of patients whose attempts to operate the pre-filled pen met protocol-defined success. (NCT02458287)
- The SPIRE-2 study is one of two cardiovascular outcome trials that are part of the SPIRE Phase 3 global clinical development program that will evaluate the investigational Proprotein Convertase Subtilisin Kexin type 9 inhibitor (PCSK9i) bococizumab in approximately 32,000 patients with high cholesterol. (NCT01975389)
Latest
news:
- • On November 1, 2016, Pfizer announced the discontinuation of the global clinical development program for bococizumab, its investigational Proprotein Convertase Subtilisin Kexin type 9 inhibitor (PCSK9i). 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 has decided to discontinue the development program, 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 cholesterol (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.
- It is estimated that the discontinuation of the bococizumab development program will have a negative impact of approximately $0.04 per share on both a GAAP and adjusted basis. Pfizer will record this as a Research and Development charge in the fourth quarter of 2016 and is incorporating this estimated impact into its updated 2016 financial guidance, which will be provided in conjunction with its third quarter earnings release to be issued this morning.
- 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. 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 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-C at 12 weeks compared to placebo among adults with primary hyperlipidemia or mixed dyslipidemia 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.
- • On April 26, 2016, Pfizer announced patient enrollment completion in the global SPIRE-2 cardiovascular outcome trial for bococizumab. SPIRE-2 is evaluating the efficacy and safety of bococizumab compared to placebo in reducing the risk of major cardiovascular events among approximately 10,600 patients at high risk for cardiovascular disease - including those without a prior history of cardiovascular events – who are on highly-effective statins or with documented statin intolerance. Based on current estimates, the SPIRE-2 study is expected to complete in the second half of 2017. In the multicenter, double-blind SPIRE-2 trial, patients with LDL-C ?100 mg/dL or non-HDL-C ?130 mg/dL were randomized to receive either bococizumab 150mg or placebo every two weeks in addition to highly-effective statins unless patients had documented statin intolerance. The primary endpoint in SPIRE-2 is time to first occurrence of a major cardiovascular event, which includes cardiovascular-related death, non-fatal heart attack, non-fatal stroke, and hospitalization for unstable angina needing urgent revascularization (i.e., heart bypass, angioplasty). The study is evaluating other endpoints as well, including the safety and tolerability of bococizumab.
- • On April 1, 2016, Pfizer announced that the Phase 3 SPIRE-AI (AutoInjector) trial of the investigational Proprotein Convertase Subtilisin Kexin type 9 inhibitor (PCSK9i) bococizumab administered with a pre-filled pen met its co-primary endpoints: percent change from baseline in low-density lipoprotein cholesterol (LDL-C) reduction at 12 weeks compared to placebo and proportion of patients successfully operating the pre-filled pen. The SPIRE-AI trial is the second study completed of the six SPIRE Phase 3 lipid-lowering studies, and Pfizer expects it will be part of the potential regulatory filing for bococizumab. Bococizumab was generally safe and well tolerated in this trial. Overall, the proportion of subjects experiencing treatment-related adverse events was similar among treatment groups. However, the trial was not designed to discern safety event differences among treatment groups. Complete study results of the SPIRE-AI trial will be presented at a future scientific forum.
Is
general: Yes
