Pfizer Inc. announced patient enrollment completion in the global SPIRE-2 cardiovascular outcome trial for its investigational agent 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.

The SPIRE-2 study is one of two cardiovascular outcome trials that are part of the SPIRE phase 3 global clinical development programme that will evaluate the investigational Proprotein Convertase Subtilisin Kexin type 9 inhibitor (PCSK9i) bococizumab in approximately 32,000 patients with high cholesterol. Many factors impact the duration of cardiovascular outcome studies, including that they are time-to-event trials, which can make it difficult to predict when the studies will accrue the required number of events. Based on current estimates, the SPIRE-2 study is expected to complete in the second half of 2017.

“Pfizer has been a leader in redefining the management of cardiovascular risk for decades, and we are applying our deep understanding of cardiovascular disease to the SPIRE phase 3 programme,” said James M. Rusnak, MD, PhD, Therapeutic Area Clinical Head for Cardiovascular and Metabolic Disease, Global Product Development. ”We have designed our cardiovascular outcome trials differently from other PCSK9i outcome trials to include both primary and secondary prevention patients at high risk for a cardiovascular event.”

The SPIRE programme for bococizumab is the only PCSK9i research program explicitly assessing cardiovascular outcomes in a broad range of high-risk primary and secondary prevention patients - including those with diabetes, chronic kidney disease, peripheral vascular disease, familial hypercholesterolemia, and history of heart attack or stroke or cardiovascular revascularization procedures – with low-density lipoprotein cholesterol (LDL-C)=100mg/dL, despite the use of highly effective statins or with documented statin intolerance.

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.

Cardiovascular disease remains the leading cause of death worldwide. High LDL-C is a known modifiable risk factor for cardiovascular events such as heart attack and stroke. Despite the availability of highly effective lipid-lowering therapies, such as statins, many patients remain at high risk for cardiovascular events. Of note, in the US, more than 70 per cent of heart attacks occur in patients without a previous cardiovascular event.

Pfizer has created SPIRE (Studies of PCSK9 Inhibition and the Reduction of vascular Events), an extensive research program to study bococizumab, its investigational PCSK9i. The SPIRE Phase 3 global clinical development program will include 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 outcome studies (SPIRE-1 and SPIRE-2).

The lipid-lowering studies are evaluating the LDL-C lowering efficacy, safety, and tolerability of bococizumab in adult patients at risk of cardiovascular events, while the two cardiovascular outcome studies are investigating the ability of bococizumab to reduce the risk of cardiovascular events in a broad range of high-risk primary and secondary prevention patients, including those with diabetes, chronic kidney disease, peripheral vascular disease or familial hypercholesterolemia, in addition to those with previous cardiovascular events such as heart attack, stroke, or cardiovascular revascularization procedures.

Pfizer’s cardiovascular outcome programme for bococizumab is the only PCSK9i research program explicitly assessing cardiovascular outcomes in high-risk primary and secondary prevention patients with an LDL-C =100mg/dL, despite the use of highly-effective statins or with documented partial or complete statin intolerance.

Bococizumab is an investigational compound and has not received regulatory approval in any country.

Bococizumab is a PCSK9i being studied for its potential to lower LDL-C and improve cardiovascular outcomes in a broad range of high-risk primary and secondary prevention patients. 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.