When PCSK9 inhibitors first came on the scene for lipid lowering, interventional cardiologist medical director of the Center for Structural Heart Disease at Detroit's Henry Ford Hospital, jumped right in -- as a patient.
As a participant in an evolocumab (Repatha) clinical trial, O'Neill saw big benefits and predicted substantial use of the new drugs in his own practice when he was profiled on ڴŮ around the time of approval.
However, that hasn't been so easy, as O'Neill told ڴŮ when we caught back up with him. A minimally-edited version of that conversation follows.
O'Neill: I am a practicing interventional cardiologist and I'm also a patient because I have familial hypercholesterolemia and I was a participant in the randomized OSLER study.
Phend: From which long-term results recently came out in JAMA Cardiology.
O'Neill: Yes, then the drug got approved, which is good and bad. It was good because it was commercially available and bad because it was impossible to get insurance to reimburse for it. I was on the study drug until last October, and that was the last study medication that I got. And it took 6 months to get the approval for the insurance company to pay for it. And the kind of stuff that they wanted, the level of detail that they wanted was honestly ridiculous.
They wrote a letter saying that they hadn't seen in a pharmacy prescription that I'd been on three cholesterol-lowering drugs and they wanted proof that I couldn't tolerate three cholesterol lowering drugs. They didn't see that my LDL was high enough but I'd been on a study drug for 4 years so it wasn't high enough. [Laughs] So it was really incredibly difficult. As a believer in the drug, I've been trying to prescribe it to my patients since commercial approval but right now I'm zero for six. I haven't been able to get a single patient on the drug who in my clinical judgment would benefit and it's primarily people who are statin intolerant, who really have terrible side effects of myositis and really physically cannot take the drug, and they haven't been taking statins and their LDLs are way out of whack. It's impossible to get them reimbursed.
Phend: You said you were finally able to get on after 6 months. Do you think that had anything to do with you being a physician and knowing how to work the system?
O'Neill: Absolutely. I got the letter, and it was a detailed letter about what it was they thought made me not qualified. I was previously at the University of Miami and I had to go back and get medical records that were more than 12 years old to try to demonstrate that without treatment what my baseline level of LDL was and I had to demonstrate to them on old records that I'd been statin intolerant and had an elevation of my CK enzyme to show I actually had myositis on statins. So that's for me because I was absolutely damned and determined that I was going to be on the drug, that there's a clear medical indication for it.
But for the average practicing cardiologist who's busy in practice and wants to prescribe the drug ... This is the first time in 40 years that I've been practicing where I couldn't write a prescription and have the patients' insurance company pay for it. And I have one of these Cadillac policies, one of these Blue Cross/Blue Shield policies that are ridiculously expensive on a monthly basis. I've never been sick before. So I've been paying to these guys for 50 years and now when I start to need some coverage, they give me this hard time. I think they're just putting a real firm block at the pricing. They're really doing a price revolt and making it impossible for patients to really get put on appropriate therapy.
And I also think that the company is charging a ridiculous amount. To charge what they're charging for these drugs is just abhorrent.
Phend: Looking at some of the other monoclonal antibodies to see what they cost per year, the PCSK9s aren't as high as some of the others, for example, what you'd use for rheumatoid arthritis. It doesn't seem like they have quite as bad a time getting approved as these.
O'Neill: I think they look at the market size and look at the millions of patients that could theoretically be eligible for the drug and they're having sticker shock.
Phend: Now with the FOURIER results, do you think that's going to make any difference?
O'Neill: I think it's going to help because the one big drawback that was not present before was, although the original ... trials showed a big reduction in cholesterol and their GLAGOV study showed a decrease in plaque size, there wasn't really any proof that hard endpoints were reduced. So the insurance companies could sort of stand under that shield that you haven't really proven that it really helps patients. It drops their cholesterol. There's so much data right now showing that LDL cholesterol has a profound adverse consequence in cardiovascular systems that it's a Flat Earth Society to say that there isn't a benefit from safely lowering LDL cholesterol. So now FOURIER shows that there's hard benefit, so that excuse for not reimbursing is gone.
Phend: But the magnitude of the effect could be an issue.
O'Neill: But it's only a 2-year therapy. If you saw, the curves are splaying and they've only gone out to 2 years. So if you continued the trial for 5 years, you'd see a huge reduction in events.
Phend: With the number needed to treat and the cost per patient per year, it seems like there would be a huge price to prevent one event.
O'Neill: I don't think that's really where the best application is. I think the best application is in people who can't or won't take statins. Because those patients are not taking anything and their LDL is through the roof. And the drug is incredibly safe. Again on a personal basis, it's safe, it's easy to tolerate, and it's easy to use, and the compliance is going to be very high because you have to use it once a month.
As a physician, the patients I'd really like to treat are the people who are having side effects or problems taking statins and who have LDL cholesterols way over 200. In those patients the event rates are very high and the number needed to treat would be much lower. This is a trial where you superimpose high doses of statins and added evolocumab [Repatha] to that. The real true benefit is going to be in patients who can't take statins.