From March 29 to 31, the American College of Cardiology (ACC) 2014 Scientific Sessions took place in Washington, DC. Amgen released new Phase III data for its emerging proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor evolocumab, and the results sparked off great enthusiasm among physicians. The results also highlight the race that is on between evolocumab, Pfizer's bococizumab and Sanofi/Regeneron's alirocumab to get to market and win over physicians.
Evolocumab was tested in the LAPLACE-2 trial on top of statin therapy in patients with hypercholesterolemia and mixed dyslipidemia and could achieve reductions in LDL-C of up to 75 percent versus placebo. That is a remarkable result in comparison with ezetimibe, which can achieve reductions in LDL-C on top of statin therapy of only around 30 percent. Four other Phase III studies evaluated evolocumab in different patient populations: as monotherapy in patients with high cholesterol (MENDEL-2); in patients with high cholesterol on risk-based lipid-lowering therapy (DESCARTES); in combination with statins and standard of care in patients with heterozygous familial hypercholesterolemia (RUTHERFORD-2) and in statin-intolerant patients (GAUSS-2). These results give evolocumab a head start on alirocumab and bococizumab. Recently, alirocumab met its primary endpoint in a Phase II study, where it reduced LDL-C about up to 72 percent on top of statin therapy, and bococizumab has lowered LDL-C levels up to 66.9 mg/dL on top of statin therapy, which equates to a 49 percent reduction based on my calculations.
But, with fairly similar reductions of lipid levels, what agent should you back as winner of the race. Evolocumab and alirocumab are likely to have enough data in niche populations to file earlier than bococizumab. However, bococizumab's outcomes trials (SPIRE-1 and SPIRE-2) are due to be completed in 2017, ahead of evolocumab's FOURIER trial, and alirocumab's ODYSSEY trial, whose completion dates are stated to be in 2018. As seen in many drug classes before, first to market advantage can have a huge impact on market share. But will the regulatory authorities need to see the CV outcomes data first.
In my opinion, the PCSK-9 inhibitors will be approved based on their positive influence on lipid levels and without outcomes data backing up mortality and cardiovascular morbidity benefit. These drugs will be very important for the high-risk patient populations, or patients intolerant to statins and those who need additional medications to control lipid levels. So, I'm tipping evolocumab to win the race.
Stefanie Hoffart, M.Sc., is a data analyst in the Cardiovascular, Metabolic and Renal Disorders team at Decision Resources Group.