Whitehouse Station, NJ - The FDA has issued a "not-approvable" letter to Merck with regard to its new combination of niacin and laropiprant, an agent to prevent flushing. The product is being developed as a cholesterol treatment while minimizing the flushing side effect of using niacin alone.
The reasons behind the rejection are not being made public by either the FDA or Merck. Merck commented to heartwire that it was not in a position to discuss the contents of the letter, but the company is keen to meet with the FDA as soon as possible to submit additional information to help the agency further assess the benefits and risks of the product. "We are trying to understand from the FDA what will be needed to respond to the issues raised," company spokesperson Ron Rogers said.
He also noted that the FDA had also rejected the US trade name of Cordaptive for the product, which will now again be known as MK-524A for the time being. "We still believe MK-524A provides an important option to manage cholesterol, and we will continue to pursue approval," Rogers stated.
Approval recommended in Europe
He added that the product last week did receive a positive opinion from the European Committee for Medicinal Products, which advises the European Medical Agency (EMEA) on drug approvals. "We therefore expect EMEA to approval the drug by July, and we will begin launches throughout Europe after that," Rogers said. In Europe, the combination drug will be known as Tredaptive. Analysts have been predicting sales of up to $2 billion per year for the combination product.
Merck stock is down approximately 10% midday today.
heartwire will be publishing a more detailed story with analysis and commentary shortly.
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| April 29, 2008 01:19 PM (EDT) |
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Big Pharma Struggles to Profit from Niacin
Big Pharma is now trying to capitalize on niacin.
Apparently, niacin, which is available without prescription for pennies, is more effective than anything else for controlling & improving lipid/blood ratios (and more).
Statin drugs, even though less effective and more dangerous than niacin, have been the most profitable drugs in history. Big Pharma’s “education” of physicians has, until recently, discouraged the use of niacin for obvious, bottom-line reasons.
The fact is that niacin’s side-effects are not at all as bad as suggested by Big Pharma. Ask anyone who’s been using niacin to control cholesterol for a few months.
See www.cholesterolscore.com for many articles and studies on this subject.
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| April 29, 2008 01:41 PM (EDT) |
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please disclose any conflict of interest
Mitch, what is your relationship to the website you mention, and what is your expertise in this area? This is a website for cardiovascular healthcare professionals only.
Larry Husten
News & Features Editor
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| April 29, 2008 02:14 PM (EDT) |
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niacin vs statins
"niacin, which is available without prescription for pennies, is more effective than anything else for controlling & improving lipid/blood ratios (and more)"
OTC niacin is not safe whereas this drug requires monitoring. It is also not the most effective therapy for patients with isolated LDL issues (statins are).
"Statin drugs, even though less effective and more dangerous than niacin, have been the most profitable drugs in history."
That's because billions of dollars have been poured into studying statins, whereas only millions into studying niacin. Double standard? Perhaps, but they are certainly not "more dangerous" or "less effective" than niacin. In fact, probably you could flip those terms and be much more accurate.
Disclosures: None |
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| April 29, 2008 07:40 PM (EDT) |
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Big Pharma?
Mitch,
believe it or not, big pharma has rarely if ever mentioned niacin in my office. I NEVER heard a thing about Niacin from anyone but the Niacin folks.
It's not Big pharma that has taught us about the tolerability profile of this patient, but rather a BIG patient population who has discontinued it. We have to listen and acknowledge this as a significant factor in the compliance issue or we do our patients a disservice. Now, I agree with you, niacin is underutilized and the fear of dealing with side effects cheats many a patient out of an opportunity for a better HDL.
Melissa |
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| April 30, 2008 07:58 AM (EDT) |
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From Taiwan
Niacin in slow released or extended released form is well tolerated as I have encouraged my patients try getting them from US. Not only their HDL profile rose appreciably but also Lp(a) improved as well. It is still a mystery to me why such an effective drug, in large dose and proven long ago, has not been on any atherosclerosis prevention( Primary or seconday) guidelines. Those who talked about "side-effects" probably never prescribed it, I suspected. Easy pointing fingers to "Big Pharma", but I put my blame on "leaders" in the field of cardiology. |
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| April 30, 2008 04:54 PM (EDT) |
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Melissa
With cordaptive rejection, what do you think about prasugrel (lilly/sankyo) rejection in the near term? I noted the FDA needs make commentary on this by June with 6 month speed review.
Any thoughts from you as an interventional cardiologist?
mc |
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| April 30, 2008 05:36 PM (EDT) |
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I believe it will be approvable but NOT a "one size fits all".
Mike,
Just to clarify, I'm invasive but non-interventional.
I believe that prasugrel will win approval for a subset of patients, but it like LMWH will likely require doseage adjustment or avoidance altogether in the elderly, renal failure patient. At some point, we have to ask ourselves the question, "when is enough enough?" We may find ourselves with a much lower acute and short term thrombosis rate at the expense of a couple of units of packed cells that no one wants us to tranfuse. So, we'll see!
Melissa |
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| April 30, 2008 09:46 PM (EDT) |
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Overstating statins v niacin?
(niacin) "is also not the most effective therapy for patients with isolated LDL issues (statins are)."
Is this based upon a study comparing outcomes of statin vs niacin or simply expected results on LDL cholesterol based on unrelated studies? If the endpoint we are looking at is LDL reduction, remember the follies of surrogate endpoints.
"billions of dollars have been poured into studying statins".... does this not create a conflict of interest between the "experts" who financially benefit from the statin studies' billions and who also author the guidelines?
I think if we look at the real DATA, there are significant interventions that are poorly studied but arguably as effective or more effective than statins which get little or no ink from the experts. The conflict of interests among "medical leaders" is often staggering, eg Hs-CRP and IVUS.
Interesting that with the expectation of Pfizer launching of Torcetrapib, Steve Cannon promised a CME on treating residual risk beyond LDL. When Pfizer got the bad news that Torcetrapib killed people, the CME was presented as measuring risk beyond LDL, the use of HS-CRP. No way for me to know but I would bet money the original intent was to promote increasing HDL and therefore Torcetrapib. If so, shame on you Dr. Cannon, we need our leaders to be responsible to the truth, not to the dollar.
With the expectation of Merck launching laropiprant, Peter Libby finally put on a CME for Medscape on HDL cholesterol and the use of niacin. Disclosure demonstrated that he had a consulting agreement with MERK. This reality makes me sad. The value of HDL has been known for decades but the experts from Harvard to my knowledge did not discuss HDL or niacin until there was a financial link between them and HDL! Dr. Libby, are you not the person I should look up to for ultimate guidance or do I need to simply read your disclosures to predict the content of your “CMEs”?
I am waiting for a CME on triglycerides. PROVE IT-TIMI 22 Trial showed us that triglycerides below 150 may be more predictive of non-events than LDL cholesterol below 70. Adding high dose omega-3 (1700 mg epa ...Yokoyama M et al. Lancet 2007; 369:1090-1098) to low dose statins provides more incremental benefit than Ideal (Pederson et al JAMA 2005; 294:2437-2445) deomonstrated with moving from low dose to high dose statins. No heroes for triglycerides? Good news, GSK purchased Lovaza the only prescription omega-3 fatty acid, maybe we can now afford to pay the experts to talk about triglycerides.
If we want to regain the respect of the healthcare consumers, we need to have some way to fund studies on non prescription omega-3 fatty acids, vit D-3, non-prescription niacin, and other inexpensive, promising interventions that are essentially ignored by big pharma and therefore also ignored by big research and "experts".
Pardon my rant, I am recovering from the flu and my filters are down.
By the way, I visited the website referenced in the first post and I fail to see any commercial aspect to it. Maybe I am just oblivious.
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| May 01, 2008 06:54 AM (EDT) |
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Triglycerides, the best indicator of what lies beneath
William B,
Glad you are feeling better.
In America, triglyceride elevation is often the best indicator of undiagnosed insulin resistant diabetes, therefore, ANY elevation in triglycerides should begat a GTT/Hbaic/insulin level. One CAN NOT practice adequate lipidology upon ANY patient without making that distinction or diagnosis.
Meissa |
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| May 01, 2008 12:31 PM (EDT) |
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Insulin levels
Melissa. The diabetologist I deal with and respect likes to use C-peptide levels because they are not affected by reduced hepatic clearance as insulin is in insulin resistant states. Have you looked into this?
Regards
Hisham |
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| May 01, 2008 05:49 PM (EDT) |
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Hmm......
Hisham,
I admit that endocrinology is the weakest link in my knowledge base so I'll take your advice and look into it! Sounds logical and I'll ask our prevention clinic physician what he likes to do and why.
Thanks for your post Hisham. Good to hear from you.
Melissa |
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| May 01, 2008 07:04 PM (EDT) |
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C-peptide
I agree with Hisham |
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| May 01, 2008 09:19 PM (EDT) |
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niacin, my favorite subject,....
Laropiprant may be a salvation for some patients,.. and prescribers. However, niacin has a longer list of positive pleiotropic effects vs statins. see Rosenberg et al 1998[?]. It actually even stimulates PPAR-gamma[?] via prostaglandin, which might shed light on some of the effects not yet fully characterized/understood: adiponectin increases 90-100%, phosphate reduced in dialysis patients ~30%, etc. Prostaglandin: "Turn that off",.. maybe not all the benefits would still be there.
SR is a bit better on Lp(a),.. and Apo(B),.. in general. Weak on HDL, especially HDL2,.. actually drops it sometimes. Reference Castelli, Am J Card 9/2004 [?], "Interview with the Editor", the "niacin 1st pass effect": The most profound effcets on HDL/HDL2 occur in up/dowm regulation of the newly characterized niacin receptor[s]. When Dr. Castelli skipped niacin every other day,.. his tot-HDL went from 70`s,.. to 90`s. Other lipid effects are somewhat reduced,.. but HDL really moves with an extended 'trough' between doses & Lp(a) seems to be the reverse. SR is real good for Lp(a). Some understanding of these issues helps explain SR`s poor HDL effects,.. and some of the safety legacy that niacin has carried on its back for 20+ years. I have seen this real-world with lipid fraction testing. A colleague of mine, an Endo, NEVER used niacin: Victim of all the mythology. Finally came back to the table as he is IR, obese and carries an HDL < 20. 1 year on 2000 mg,.. 45. Mine was 45 1/04,.. 86 now with #X increase in HDL2,.. still increasing on ecery lab: Niacin is funny like that. NO FLUSH = placebo Except on non-lipid parameters. Example: intestinal phosphate absorption.
ER / IR nearly identical on all lipid fractions, sodium/phosphate transporter, adiponectin increases, ADMA decreases, pattern B to A conversion etc.
50% of all pattern B carriers have trigs < 150,.. 20% of all patterb`s have trigs < 90. That last phenotype one is my dad. Insulin resistance lurks everywhere,.. even with low trigs and 'reasonable' BMI`s. dr. bale has a lot of insight there: Thank you Dr. Brad ! A 2 hr post-prandial > 140.
high trigs, IR, yes. Trigs , 150 "in the clear",.. NO.
Best tutorial on RRR I ever heard was the 'tear a sheet of paper in half' demo. Tear off a third,.. that`s 33% RRR. Tear a third of that piece off, again 33%. But the total RRR form baseline is 33% + [33% X 33%]= 33% + 11% = 44%. that is not 66%,.. and the ARR is quite small. Dr. Superko really puts that in perspective. % still having events in placebo vs treatment arm,.. lifetime risk of an eent vs. 3-5 years in RCT.
As to CKD & especially ESRD, 3 of my mentors warned me, repeatedly, about statins & Lp(a), apo(a) fragments and LMW vs. HMW Lp(a).
wanner et al 2005 FATAL ischemic stroke doubled in the statin arm. Just an observation. If I were stage 5 CKD, I`d avoid that statin. Simva seems to be Lp(a)-neutral based on non-industry funded data. That is a mysterious effect, for sure. Rosuva as well. Want to make the rep nervous, ask them for their MSL letter on Lp(a).
Just waxing provocatuer here,.. not making any claims as to what/who is right or wrong.
No disclosures worth mentioning,..
All friends & family on 1-2 gms/d niacin. Some take Carlson Labs some take Rx.
PS There exists no true OTC niacin,.. they are all supplements. carlson is very reliable. No ties,.. I just like Carlson Labs. the 50 mg IR is a real 'nifty' starter for sensitive patients,.. til they tachy down to not flushing. Look @ any CIMT @ baseline on any patient, then again after 2-3 years of 1-2 g/d niacin: Echolucent vs echogenic: Tromso.
[Speaker steps off soap-box: Niacin defended] |
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| May 01, 2008 09:28 PM (EDT) |
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Cool tip
I was reviewing ADA abstracts awhile back and I uncovered a 'gem/rough-diamond'. Reference not in hand @ the moment,.. but, I promise to get back on that.
FFTT vs. OGTT.
Simple glucose meter/finger-sticks & some 'practice'. Amazingly good correlation. No insurance, no $$. A few testing strips is all. Sometimes they even remember to bring back the monitor for someone else to use. Direct patient to "misbehave",.. have a high-carb/high-trans-fat "happy meal". 2 hours later do a finger stick. Compare to baseline fasting. Repeat both readings a few times and bring back 'log' into office.
FFTT = Fast Food Tolerance Test. No $$ burden to patient. Cheap screening tool. Nothing is perfect in this world,..but for a cash patient who my "gut" is worried about,..? |
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| May 01, 2008 09:44 PM (EDT) |
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This is your HDL........this is your HDL on drugs:
My HDL 1990's - 25
My HDL on exercise 50
My HDL on exercise + Rosuvistatin 64
Reduction in plaque burden..priceless.
oops, that was another commercial.
No industry ties.
Melissa |
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| May 02, 2008 07:12 AM (EDT) |
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| May 02, 2008 08:34 AM (EDT) |
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:)
Thanks Dan. Glad you didn't mean "little ole lady!".
Melissa |
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