Pfizer Discontinues Investigational PCSK9 Inhibitor Bococizumab

In a surprising announcement, Pfizer has said they will no longer continue to develop their investigational PCSK9 inhibitor bococizumab and have halted two ongoing cardiovascular outcomes studies.

In a statement issued today, Pfizer said they have “observed an emerging clinical profile that includes an unanticipated attenuation of LDL-cholesterol lowering over time.” Along with the weak data, the company reported a higher degree of immunogenicity and a greater incidence of injection-site reactions with bococizumab compared with other drugs in the class.

The development program for bococizumab, known as the Studies of PCSK9 Inhibition and the Reduction of Vascular Events (SPIRE), includes six completed trials to date, but the data suggest bococizumab “is not likely to provide value to patients, physicians, or shareholders,” according to Pfizer.

To date, the US Food and Drug Administration and European regulatory agencies have approved two monoclonal antibodies for the treatment of high LDL cholesterol levels: alirocumab (Praluent, Sanofi/Regeneron) and evolocumab (Repatha, Amgen). Pfizer’s drug was expected to compete with alirocumab and evolocumab, potentially driving down the more than $14,000 per year price of the medications. The Medicine Company and Alnylam Pharmaceuticals are currently working on a twice-yearly injectable monoclonal antibody, but development is still in a relatively early stage. 

The SPIRE-1 and SPIRE-2 studies, the large cardiovascular outcomes trials testing whether the reduction of LDL cholesterol with bococizumab reduced hard clinical events, would have included approximately 26,000 patients and have both been stopped. This past April, Pfizer announced that SPIRE-2, a 10,000-patient study in high-risk patients, had completed enrollment.

The company said they will ensure all regulatory authorities are informed of their decision to stop development and physicians given information on appropriate next steps. Importantly, they plan to make the data available to study leaders for analysis and will present these results at future cardiology meetings.

This is the second high-profile flop in the last decade for Pfizer in the cholesterol field. In 2006, the company was forced to abandon torcetrapib after a large phase III study revealed a significantly increased risk of mortality and cardiovascular events among those who received the CETP inhibitor.