James Underberg, MD: The Alirocumab-Evolocumab Race

Since PCSK9 inhibitors alirocumab (Praluent) and evolocumab (Repatha) were approved for cholesterol management by the US Food and Drug Administration (FDA) in 2015, the therapies have been frequently compared.

But what will define a physician’s preference for one or the other? Internist James Underberg, MD, a clinical assistant professor in the Department of Medicine, NYU Langone Health, told MD Magazine® in an interview that the full story for either drug is yet complete.

MD Mag: Could upcoming treatment guidelines dictate clinical preference of alirocumab versus evolocumab?

Underberg: We're a little hampered by the fact that the FOURIER trial has been presented, published, and produced a host of post-hoc analyses and additional publications. The ODYSSEY trial has been presented, but we have not yet seen a peer-reviewed document and a published article, never mind a variety of published post-hoc analyses.

So I think the data is less sparse with alirocumab than evolocumab, so I think it would be very difficult to parse out indications or recommendations when you don't really have the full story from both drugs. I think the drugs work in a very similar mechanism. Cost is always a concern.

I don't know what we're going to see in the next set of guidelines, but potentially at least including cost in the way we think about and understand additional or incremental medication allotment—it might be a key part of that.

So, where cost lays out in the difference between these 2 drugs may play a role in choice down the road. But certainly as of today, that has not weighed, as well as made its way into our current guidelines and thinking.

What is the significance of either drug seeking further cardiovascular comorbid indications?

When you look at indications for medications, I think it's often based on the way trials were designed. And so at least currently, we have 2 trials that were designed in patients with atherosclerotic cardiovascular disease.

Unfortunately, there was a trial going on with a third PSCK9 inhibitor that was looking at high risk primary prevention patients, and was not followed through to completion because of a loss of efficacy over the course of the first year that the patients were studied. The drug wasn't unsafe, it just seemed to lose its benefit to the degeneration of antibodies.

So, the only population that's really been studied in a randomized prospective fashion is the highest risk ASCVD population. We would all love to see an expansion of the indication to what we assume to be equally important to treat: high risk primary prevention patients, the diabetic patient with hypertension, or smoking with a patient with subclinical atherosclerosis, patients with elevated lipoprotein A, etc. I hope as time goes forward, trials like that are designed, that will better inform us as to whom we can additionally use these drugs with an expected benefit.