FDA Panel Endorses Second PCSK9 Inhibitor for LDL Cholesterol
The FDA has recommended approval of another PCSK9 inhibitor as an effective and relatively safe means of lowering bad LDL cholesterol.
The Endocrinological and Metabolic Drugs Advisory Committee voted 11-4 to recommend Amgen’s Repatha (evolocumab) as a treatment for patients with high cholesterol and a high risk of cardiovascular events.
The vote followed last week’s 13-3 recommendation for Sanofi/Regeneron’s Praluent (alirocumab) for the same patient population, as well as for patients with familial hypercholesterolemia, a rare genetic disorder that causes elevated LDL-C.
For Repatha, the panel voted separately on the FH indication, giving it unanimous thumbs up. In both cases, the panelists overwhelmingly said that the benefits of lowering LDL-C outweighed any potential risks, particularly in this group of patients.
In discussion leading up to the votes, panelists focused mainly on Repatha’s efficacy and whether there was a danger if levels fell too low.
Harvard Medical School’s Marc Sabatine, who represented Amgen, pointed out that the company doesn’t have any data showing a downside for low LDL levels. Some committee members agreed with Sabatine’s assessment. Kenneth Burman, with Georgetown University, said there is no compelling data that low LDL cholesterol is detrimental, but committee Chairman Robert J. Smith, with Brown University, called it an open question.
Scott Wasserman, vice president of Amgen, said patients should undergo statin treatment before being prescribed Repatha. Amgen is proposing that the drug be given at either 140 mg every two weeks or 420 mg monthly along with statins, another cholesterol drug or to patients who can’t tolerate statins.
The committee also expressed concerns that physicians would not be able to titrate the drug to change the dosage and might drop statins despite their benefit to patients.
In background materials released ahead of the meeting, the FDA said Repatha effectively lowers LDL cholesterol. Patients taking Repatha (evolocumab) in one study saw their LDL-C drop 23 percent at 12 weeks, versus an 8 percent rise in patients receiving a placebo.
But the agency questioned the long-term safety of the drug, saying the safety data is based almost entirely on patients at 12 weeks duration. Amgen conducted one 52-week placebo-controlled trial in which 599 patients received Repatha, but many of those weren’t at high risk for cardiovascular events. — John Bechtel