Pfizer Inc. announced two additional phase 3 bococizumab trials, SPIRE-HR (HighRisk) and SPIRE-FH (Familial Hypercholesterolemia), met their primary endpoint, demonstrating a significant reduction in the percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at 12 weeks compared to placebo among adults at high and very high risk for cardiovascular events who were receiving a maximally tolerated dose of a highly effective statin.

SPIRE-HR and SPIRE-FH are the third and fourth of six SPIRE lipid-lowering phase 3 studies to complete and show positive results. The two remaining SPIRE lipid-lowering studies are anticipated to complete later in 2016. Both SPIRE-HR and SPIRE-FH continued for 52 weeks to assess the longer-term efficacy and safety of bococizumab, an investigational Proprotein Convertase Subtilisin Kexin type 9 inhibitor (PCSK9i), in patients at high and very high risk for cardiovascular events.

“These positive results add to the growing body of scientific evidence in support of bococizumab for lowering LDL-cholesterol in patients at high risk for cardiovascular events,” said James M Rusnak, MD, PhD, chief development officer, cardiovascular & metabolic disease, Pfizer Global Product Development. “The high burden of cardiovascular disease suggests that more treatment options are needed to help lower cholesterol and reduce cardiovascular risk in these patients. Our goal with the extensive SPIRE clinical program is to evaluate whether bococizumab not only reduces cholesterol, but also reduces the risk of cardiovascular events in a broad range of high-risk patients, including those without a history of heart disease.”

The double-blind, randomized, placebo-controlled, parallel-group, multicenter, 52-week study evaluated the efficacy, safety and tolerability of bococizumab to lower LDL-C compared to placebo. The study included 711 adults with primary hyperlipidemia or mixed dyslipidemia at high and very high risk for cardiovascular events receiving a maximally tolerated dose of statin therapy whose LDL-C =70 mg/dL.

Patients in the SPIRE-HR study were considered at high and very high risk for a future cardiovascular event if they had a known history of cardiovascular disease, including coronary heart disease or atherosclerotic diseases, diabetes or chronic kidney disease.

The SPIRE-FH double-blind, randomized, placebo-controlled, parallel-group, multicenter, 52-week study evaluated the efficacy, safety and tolerability of bococizumab to lower LDL-C compared to placebo. The study included 370 adults with heterozygous familial hypercholesterolemia (HeFH) and at high and very high risk of cardiovascular events receiving a maximally tolerated dose of statin.

HeFH is a difficult-to-treat genetic condition that causes high LDL-C at birth putting patients at high risk for cardiovascular events at an early age.

Patients with HeFH in the SPIRE-FH study were considered at high and very high risk for a future cardiovascular event if they had a known history of cardiovascular disease, diabetes or chronic kidney disease and an LDL-C = 70 mg/dL or without a known history of cardiovascular disease, diabetes or chronic kidney disease with an LDL-C =100 mg/dL; patients were required to be on the highest locally approved dose of an eligible statin or on the maximally tolerated dose.

Bococizumab was generally safe and well tolerated in both trials. Overall, the proportion of patients experiencing adverse events was similar among treatment groups, with one exception of a higher incidence of injection site reactions seen for patients on bococizumab compared to those on placebo in both trials. The majority of reported injection site reactions were mild.

Complete study results from the SPIRE-HR and SPIRE-FH trials will be presented at a future scientific forum and will be part of the potential future regulatory filing for bococizumab.

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 programme 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 high risk for future 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 phase 3 programme for bococizumab is the only PCSK9i research programme with a dedicated CV outcomes study explicitly assessing cardiovascular outcomes in high-risk primary and secondary prevention patients with an LDL-C =100 mg/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.