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Pr Evan Stein: statin intolerance and hypercholesterolemia

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MD-FM INSIGHT

Statin intolerance and hypercholesterolemia

Gauss trial: PCSK9 antibody reduced LDL in statin-intolerant patients

 

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Clementine:

Hello! You’re on MD-FM INSIGHT, the first web radio for e-Continuing Medical Education.

 

Clementine:

Today, we are offering you a "Question & Answer" program devoted to a new approach to lowering LDL levels in patients who cannot tolerate statins: Researchers are investigating the use of a new agent, a monoclonal antibody called AMG-145.  

 

Clementine:

To find out more about this approach, we interviewed Dr. Evan Stein, from the Metabolic and Atherosclerosis Research Center in Cincinnati, OH. Last November, he presented the results of the GAUSS study at the meeting of the American Heart Association in Los Angeles. In this study, he and he team compared the investigational antibody AMG-145 to the conventional drug, in statin-intolerant patients at high and moderate cardiovascular risk. 

 

Clementine:

Dr. Stein, lets jump right into your study. First of all maybe tell us why you compared AMG-145 to ezetimibe?

 

Stein: If patients can’t tolerate statins or can only tolerate very low doses, mostly because of muscle related side effects, they have very little options. The only real tolerable option is ezetimibe, a drug which blocks cholesterol absorption, and so we used that as a positive control, and one of the 5 arms was on ezetimibe alone and placebo injections of AMG-145. 1 of the 5 arms was on ezetimibe and real AMG-145. The other three arms were on AMG alone at different doses: 280, 350 and 420 mg, and these drugs were given subcutaneously every 4 weeks. To get into the study the patients had to have proven muscle-related side effects on previous statins: 100% of them had been intolerant to at least 1 statin, about 70 to 80% had been tried on 2 statins, and even a third had been brave enough to try a third statin and not been able to tolerate it

 

Clementine:

And so what did you see in terms of LDL reduction?  

Stein: In the ezetimibe arm alone we saw the expected 15%, ezetimibe traditionally gets 15 to 18% LDL reduction. In the AMG alone arms, at the lower dose of 280 going up to the 420, that ranged from an LDL reduction of 41 percent to the highest dose was 51 percent, and in those patients who received both ezetimibe and AMG 145 there was a 63 percent reduction in LDL cholesterol

 

Clementine:

So this is really quite a large jump for this difficult to treat population. What have been your main conclusions? Is this at a stage where we can say lets go ahead?

 

Stein: It certainly meets an unmet medical need for many millions of patients. 10 to 20% of statin takers can’t tolerate the drug, if you figure that in the US alone there are about 20 million people who need statins or who are given statins that’s 1 to 2 million people, and in Europe obviously there’s a large number of people as well. So that if you cannot tolerate a statin your options are very limited of ever getting to optimal LDL reduction, and we know that LDL is probably the single most effective modifiable risk factor for reducing your risk of heart disease, if you’re at high risk of if you’ve got coronary disease, so you need to get to a certain LDL level. And this drug looks like it provides at least a very promising alternative. It’s going to require much larger confirmatory studies and of course long term safety data just as we did when we developed statins

 

Clementine:

That was going to be my next question --How well tolerated was it? 

Stein: This study was a phase 2 study, and that’s really an efficacy study, all phase 2 studies in lipidemia are really to find a dose and to find a patient population that you think will benefit from the drug. And then you have to go into phase 3 and phase 3 is basically safety. LDL is a very robust and validated surrogate and most regulatory agencies in the world, the AMA, the FDA, all accept LDL as a proven surrogate for reducing coronary artery disease. So now it requires 2 to 3 years of large scale safety studies to make these drugs have no adverse effects

Clementine:

What’s the take home message for the practicing community today? 

Stein: “For statin intolerant patients and patients who can’t get to goal on maximum drug therapy, and those are severe hypercholesterolemics or patients with inherited abnormalities, there are not a lot of alternatives, and its certainly the muscle related side effects that drive the average practicing clinician crazy because these patients cant tolerate and yet need medication, that probably in three to four years time they will have a real alternative

 

Clementine:
This show is over. By visiting the MD-FM website, you can check out the themes of the programs we will be offering you regularly.

See you soon on MD-FM.

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