Merck Expands Study For Failed Cholesterol Drug
31 CommentsBy Ed Silverman // October 18th, 2008 // 9:56 am
Desperate to regain its edge in the cholesterol market, Merck is adding another 5,000 patients to a key clinical trial for its Cordaptive drug in hopes obtaining regulatory approval as soon as possible. The pill contains an extended-release form of niacin, which is a vitamin, and a chemical called laropiprant to stop flushing, a common reaction to niacin.
You may recall that FDA approval was delayed last June because the agency wants to see more data. For Merck, the hitch is that results of its cardiovascular outcomes study called THRIVE (Treatment of HDL to Reduce the Incidence of Vascular Events) won’t be complete until January 2013 (back story). This meant the drugmaker couldn’t file a complete response until 2010. Now, though, Merck is expanding the trial to include 25,000 patients between ages 50 and 80.
“Recruitment to THRIVE is going well, but the expansion of this project is very good news. In terms of numbers, bigger is very much better,” says Jane Armitage, one of the principal investigators, at University of Oxford Clinical Trial Service Unit, in a statement. “This enhancement will give us a more powerful tool with which to assess this intervention for the benefit of heart patients everywhere. The study is scheduled to end in 2013, but with these additional patients, we hope that it will be able to report sooner.”
The trial is recruiting in the UK, Scandinavia and China, and 3,000 additional participants will be sought in China, and 1,000 in Scandinavia and the UK.
Gianna
why in hell would someone pay hundreds for a pharmaceutical when you can buy supplements of niacin (no-flush as well as the ordinary kind) for pennies a day…
and it works really well…
this is sickening.
Steve
I completely agree. I use Niacin, and it has done very well in controlling my cholesterol. But you do have to have blood tests every 3 months or so, to make sure you have no liver problems. In RX strength, this MUST be checked.
Nathan
As Ed pointed out above, Cordaptive is more than just Niacin. Niacin along causes itching, redness, flushing, and hot flashes. Cordaptive combines Niacin with a molecule that prostaglandin-D2 receptors (Laropiprant). This has the effect of blocking the above side effects.
The recommended daily allowance of Niacin is 16 mg. In contract, Cordaptive is a dose of 1000 mg — which would easily cause the above side effects were it not for the addition of the Laropiprant.
See this link for more info:
http://cholesterol.about.com/od/prescriptionmeds/a/cordaptive.htm
Justice in MI
Thanks, Nathan. I don’t intend to put you in the role of spokesperson, but I was struck by this paragraph:
‘The major side effect noted in the study so far was the flushing effect experienced with nicotinic acid. Roughly 4.8% of individuals participating in the study had to discontinue the Zocor/Cordaptive combination due to flushing, whereas the 8.7% of participants only taking Cordaptive stopped taking the drug due to the niacin-induced side effects. However, it is important to note that while flushing was still present in these patients, the incidence of experiencing flushing while on niacin alone would likely be much higher.’
re: the 8.7 % who discontinued - the phrase, ‘due to the niacin-induced side effects’ is ambiguous. I understand it is probably intended to be read as flushing. But it is the kind of vague and all-inclusive language that raises questions in those who know how carefully releases of this sort are worded.
Former pharma Marketing Exec
To the point of the first two posters here.
You can and should use Niacin supplements rather than pay an arm and a leg for this drug. However, you should also alter your diet.
So, niacin, diet and exercise. If you do it right, and do not have a genetic component to your HDL, you can be healthy and off medications in a couple of years….
It is your body - good choice, bad choice, YOUR choice!
Lilli
Merck and all Pharmaceutical Companies. are not really interested in preventing and really protecting the health of the people. Zocor has silently killed many individuals—because the medical profession does not tell the truth about adverse events. Merck is only interested in making money. The federal and State Legislature has for ages allowed this to happen—elected and appointed officals are greedy and corrupt—look no further Henry Paulson. Expect the same unethical issues with the medical profession
Nathan
Former pharma Marketing Exec seems to be a man of many talents. Now he is offering medical advice! I guess he must have earned his MD shortly after loosing his past marketing job…
You do realize that you couldn’t POSSIBLY pay “an arm and a leg” for this drug, right? It isn’t on the market!!
Justice in MI
Anyone know who the flushing rate of this drug compares with ‘no flush’ niacin?
Steve
Nathan,
You write a lot, fill up a lot of space, pretend to be an expert in everything, yet, you have time for jibes. Please send us another demeaning remark, right away! That seems to be your forte.
Don’t change, you are a breath of stale air.
Nathan
Justice,
I was looking for that and couldn’t find it. If you happen to find it, please post. That seems to be the entire premise of this drug.
Steve,
Please call me on the carpet next time I offer medical advice. (I don’t believe I have) My expertise is drug mechanisms. That’s my 8-5 job. FPME has never claimed to have any medical training yet he clearly is offering medical advice. Read his post again: “You can and should use Niacin supplements rather than pay an arm and a leg for this drug. However, you should also alter your diet. So, niacin, diet and exercise. If you do it right, and do not have a genetic component to your HDL, you can be healthy and off medications in a couple of years….”
Steve
Nathan,
Okay, I just thought you sometimes get over assertive.
As I stated in an earlier post, I use Niacin, (three grams a day). If not tested regularly and under the supervison of a doctor, it could very well cause permanent damage to the liver.
I recall my doctor telling me if everyone could use Niacin without those temporary side effects, (flushing, hot flashes, etc) it would always be his choice. Niacin is a natural vitamin (B family).
If patients were to give the Niacin a chance, it really does work. The side effects do diminish and eventually disappear. The other benefit, it really is cheap.
By the way, I am very involved in the biotech field (21 years). Just the money end of it. I am well aware of what is going on (drugs), as I need to know who the competitors are and how they stack up against one another. That’s why I read different web sites and blogs.
laura
Nathan,
Just because your screen name is “Nathan”, I don’t assume that you sell hotdogs for a living. It’s probably not a good idea to make assumptions based upon screen names.
Salmon
25,000 subjects!
What everyone seems to be missing is that the only reason you would need this many people is because the effect is so small that you can’t detect as significant difference otherwise.
For example if half are on niacin and half Merck’s drug and 15 people have events on Niacin and 10 on Merck’s drug that’s a 1/3 improvement but it’s only 5 people and many many times that would have side effects. Plus if there isn’t a placebo arm you can’t even determine what the true side effect rate is. Maybe there are more deaths on both drugs as compared to placebo.
The devil’s in the details but a study of this size is clearly a red flag.
Salmon
Nathan
Salmon,
That’s a good point — but I think you are also missing two major points.
1) Heart attacks are (relatively) rare. If you are measuring reduction in cholesterol, that would require much smaller trial. But pharma has been criticized again and again for going after “secondary endpoints” such as cholesterol and blood pressure. Instead, Merck is going all-the-way for this study: they are looking for efficacy in a PRIMARY endpoint. This requires a much larger clinical trial because the actual rate of heart attacks in the general population is relatively low. (everyone has a blood pressure and cholesterol level — but only a small fraction of those 25,000 people will have a heart attack - a few hundred maybe?)
2) Cardiovascular drugs are held to a much higher standard by the FDA than other classes of drugs. (because they are used by so many otherwise healthy people) Therefore, Merck needs to have a VERY good understanding of the side effects of this drug — even the very minor side effects that will only affect a small percentage of those taking the drug. Trying to find side effects that may occur in only 1-2% of patients requires very large clinical trials.
The scope of this trial is exactly why many companies are pulling out of cardiovascular research. The rewards are huge — but the investment required to get a drug to market is absolutely through the roof.
Nathan
One thing that I think is interesting (and worrysome) about this study is Ed’s final sentence: “The trial is recruiting in the UK, Scandinavia and China, and 3,000 additional participants will be sought in China, and 1,000 in Scandinavia and the UK.”
Presumably this drug will be marketed (largely) to “westerners” who have a very different diet and lifestyle from those in China and Scandanavia. Does anyone worry that the results observed in those countries won’t necessarily translate to the US and Western Europe?
The Caped Crusader
More patients will allow a tiny difference to be detected in their study. When you see trials of this magnitude you can pretty much be assured they know they have a pretty ineffective drug or a drug that for most patients has little benefit for its relative cost. Just saying.
Justice in MI
“Does anyone worry that the results observed in those countries won’t necessarily translate to the US and Western Europe?”
Yes, I was wondering about that.
Otherwise, tried to get the flush percentage for inositol niacina..whatever (’flush-free niacin’), but couldn’t find it. Of ocurse, this stuff is essentially unregulated.
Salmon
Nathan,
I think you made my point for me.
Heart attacks are rare events so is it really worth it to treat 20,000 people with drugs long term so as to get a benefit in 50 more people? That’s a lot of money and a lot of side effects for a most people who will get no benefit whatsoever.
As for rare side effect 1% is a common side effect not rare, and you only need 300 people to detect a 1% side effect with 1% incidence.
Regulatory requirements are 500 people for 6 months and 100 for 1 year so there is really no interest in finding those rare side effects that you need to study thousands of people for. In fact one FDA representative John Senior said at a meeting in Italy that we can’t call a drug that kills 1 in 10,000 people toxic. Plus if it’s killing 1 in 10,000 it may be maiming anywhere from 1 in 100 to 1 in 1000.
As for cardiac patients being otherwise healthy I don’t think so. What about all the diabetics and psych patients who have cardiac problems because these illnesses run together. In fact most chronic drugs are sold to people who have multiple different illnesses not just one. This seems to be because what ever is causing one problem may also be involved in the others.
No the standards in CV meds are high because there’s so much already available that has a long safety history and it’s difficult to show a benefit.
Former pharma Marketing Exec
Nathan,
Just for the record I do have MANY talents.
Secondly, the drug “will” cost way much more than niacin supplements and good exercise and diet costs. There is no reason for it not to, it is a business - we all get that!
Like I mentioned, as long as there is no genetic component to the HDL (which then must be treated by a doctor, and probably drugs), then good diet, exercise and regular niacin supplements should just do the trick.
Sorry Nathan, I don’t think people should go see the doctor you have paid to sell me a drug that I do not need. The very same doctor who will not point out the obvious to the “patient” i.e. - diet and exercise…
Oh, and let me just say the diet should include wholesome foods, mostly organic, low in trans fats. Lots of fruits and veggies (showing off my talent as a nutritionist….)
Nathan
Salmon - I completely agree with your last sentence: “the standards in CV meds are high because there’s so much already available that has a long safety history and it’s difficult to show a benefit.”
In a nutshell, that’s exactly why this clinical trial is so large! In the current FDA environment, Cordaptive will have to be shown to be as safe (or safer) than existing medications and it will also have to show real benefit (not just in surrogate endpoints). That is a very high bar since this is an area that pharma companies have largely succeeded at over the last decade. Are you arguing that they shouldn’t even TRY to show a benefit over existing treatments? Or are you arguing that the marginal benefit of this drug isn’t likely to be worth the cost to patients? I guess I’m not sure what your criticism of this trial is. It seems that Merck is in a corner: Either do a huge clinical trial or just give up. Neither scenario is appetizing – they had to choose one or the other.
harpy
Geography people! Last I checked, Scandanavia is in western Europe. And as to China - get used to it white man. People of color, women, and children have been taking drugs tested on white males for years and years - if there are side effects for you, you’ll find out the same way we do - by taking it.
And where do you think Americans come from anyway, Nathan?
Justice in MI
Yikes. Dare I provoke the harpy?
Although I did know where Scandinavia was, my own thought had to do with genetics as that may impact efficacy. Of course, everyone is talking about genetic ‘customizing’ of meds. So it seemed conceivable to me that gene pole ‘nodes’ might lead to different results for different drugs. Yes, ultimately one goes by one’s own experience. But if large claims are being made, it might become relevant; just as we know much of the statin claims do not apply to women.
Where do Americans come from? Ellis Island.
CV MD
Gee, I wonder if Merck had an administrative analysis performed to assess population size. Such an analysis would hav been reviewed by a data Monitoring Committee, who then provides recommendations to Merck. If this was done, then Merck is not being “transparent” with their increase in the size of the study. They could be doing it for the potential to pick up very small differences between the groups. Or because there are not enough events happening during the trial, meaning that both regimens are effective.
Justice in MI
…and slave ships, rio grande, bering straits, small towns Sarah Palin likes, comet dust, and the like…
harpy
I had a chance to fact check myself and must confess I was thinking along old Cold War lines. Current thinking has Scandinavia in Northern Europe now that it is convenient to speak of Europe as having four corners.
And I think we were thinking along the same lines, JiM, except that I, as a woman of Scandinavian descent, was looking at it from the other side of the fence as I am already at a disadvantage as far as whether or not medications will “work” for me since the majority of research is aimed at white men. I think it was the ethnocentric and, seeming to me, callous nature of Nathan’s question that peeved me. China is the big bonanza for pharma now and I wouldn’t be surprised that more clinical testing and medications will focus on Asian types. I mean, ~360 million Americans vs. ~1 billion Chinese = tough luck whitey (not to mention that a lot of those Americans aren’t white or male either).
Nathan
harpy,
First, I wasn’t trying to be zenophobic. It seems to me that you and I can both agree that the BEST scenario is to run clinical trials in the intended market population. This isn’t always feasable, obviously. But it should be at least considered.
Second, I don’t where you get the notion that previous clinical trials have been primarily on “white males”. Do you have data to back this up? I have read that it is difficult to recruit minorities into clinical trials. But I’ve never heard of gender bias in clinical trials.
Finally, why do you assume that I am a white male? You seem to have some biases yourself…
Nathan
harpy,
One other point: In my perspective, the shift of clinical trials overseas has more to do with cost and regulation of clinical trials than it does with marketing. While China and India are viewed as a huge potential market, the more luctrative aspect is that it is cheaper to conduct clinical trials in China/India than in the US.
To be fair, I also should say that Ed’s last sentence is a little ambiguous. It’s not clear whether the entire 25,000 person clinical trial is being conducted in China/Scandanavia/UK, or if the current recruiting is going on in those countries. For all I know, they could have already recruited 15,000 people in the US and now the last group of people needed are from these other places.
Laurita
Hi All;
Nice to see all this discussion, except for some topics not related to the main issue. Is good to know, and I believe Merck could take some good points to discuss internally.
Salmon
Nathan,
In essence I am “arguing that the marginal benefit of this drug isn’t likely to be worth the cost to patients”.
That’s not to say that I don’t think similar trials for other CV drugs in the future shouldn’t be done. My point is that even if the trial is done and efficacy is shown the marginal benefit in comparison to the adverse events and cost to so many people may not justify prescribing it.
One study has already failed. If it had been a positive study the equation at this point would look much different. Instead it didn’t work and so they have to racket up to study to have huge numbers of people to chase a statistical difference that is not likely a clinical improvement in treatment. Thus it looks like a therapy based on marketing and sales and not on a therapeutic or societal benefit.
Justice in MI
I would stay away from Scandinavians.
BTW, xenophobia is the fear of strangers.
Zenophobia is the fear of one hand clapping.
harpy
“One thing that I think is interesting (and worrysome) about this study is Ed’s final sentence: “The trial is recruiting in the UK, Scandinavia and China, and 3,000 additional participants will be sought in China, and 1,000 in Scandinavia and the UK.”
Presumably this drug will be marketed (largely) to “westerners” who have a very different diet and lifestyle from those in China and Scandanavia. Does anyone worry that the results observed in those countries won’t necessarily translate to the US and Western Europe?”
“It seems to me that you and I can both agree that the BEST scenario is to run clinical trials in the intended market population.”
Ok - if people from the UK, Scandinavia, and China don’t fit your idea of the “market population” in the US then where does? I would think that European and Asian would hit a pretty broad range here in the US. Moreso than say, Peru or Micronesia.
“…the shift of clinical trials overseas has more to do with cost and regulation of clinical trials than it does with marketing. While China and India are viewed as a huge potential market, the more luctrative aspect is that it is cheaper to conduct clinical trials in China/India than in the US.”
You were bemoaning the fact that the results may not translate to - you(?) - the market population? I think, and my point was, in the near future you and I will slowly cease to be the target market. So, combining your point of cost and regulation with my point of a HUGE potential market - why do you still think Americans (which we still haven’t defined) are the target audience?
“In the past, most drug testing had been done on white men. This means that some groups, such as African Americans, Hispanics/Latinos, American Indians, Asians, Pacific Islanders and women,(not to mention children - my addition) had not always been included in the tests done on drugs. But sometimes drugs work differently in these people than on white men. So FDA wants people from many different groups included in these studies.” FDA website
Finally, am I wrong that you’re a white male? You didn’t exactly say. And if you think I’m not biased, you haven’t been reading my posts.