As with alirocumab, the panel was asked to discuss whether the impact on LDL-C with evolocumab was sufficient to demonstrate an effect on clinical outcomes; historically, the FDA has considered reductions in LDL-C sufficient to establish the effectiveness of a lipid-lowering drug and does not require that benefit be shown in a CV outcomes trial before approval, “provided the reduction is sufficiently robust” and the product does not have any safety issues that raise concerns about the benefit-risk profile, according to the FDA. Although several panelists said that, while the drug targets LDL-C via a mechanism that is fairly close to the statin target, which provided more confidence in using LDL-C as a surrogate for CV benefit, they said this question can only be answered definitely with the CV outcomes trial.
The CV outcomes study, the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), has been fully enrolled, with about 27,500 patients, and is expected to be completed no later than 2017, according to Amgen. The study also will provide safety data in more than 5,000 patients with LDL-C levels below 40 mg/dL.
The FDA usually follows the recommendations of its advisory panels. The FDA panelists had no potential conflicts of interest. A decision is expected by Aug. 27. If approved, Amgen plans to market evolocumab as Repatha.