Thursday, January 21, 2010

Drug Industry Innovation: GSK's LOVAZA Vs. OTC Omega-3 Fatty Acid Supplements

The pharmaceutical industry is often criticized for developing new Rx drugs having little value over current medications. Such drugs are called "me-too" drugs because of their similarity to existing Rx drugs. Glaxo has now taken this to a completely NEW level: developing an Rx drug that is a "me-too" of existing over-the-counter dietary supplements. I am talking about LOVAZA, aka omega-3-acid esters approved by the FDA for the treatment of high triglycerides. Here's the ad for LOVAZA, which I cut out of this week's Newsweek Magazine (click on it for an enlarged view):


LOVAZA seems identical to the Member's Mark brand of Omega 3 Fish Oil that I can buy at my SAM's Club store for about $18 a bottle. This bottle includes 400 Softgels and will last me 3-4 months if I take the recommended 4 1000mg softgels per day -- that works out to be about $5-6 per month.

Is LOVAZA different than the OTC (over-the-counter) product I have in my kitchen cabinet? Here's how they compare (check out the LOVAZA package insert here):

Dosage Form: MM, 1000 mg softgel; LOVAZA, 1000 mg softgel

Dosage: MM, 4 softgels per day; LOVAZA, 4 softgels per da

Active Ingredients: MM, 300 mg of 3 Fatty Acids (EPA and DHA); LOVAZA:  Each 1-gram capsule of LOVAZA contains at least 900 mg of the ethyl esters of omega-3 fatty acids sourced from fish oils. These are predominantly a combination of ethyl esters of eicosapentaenoic acid (EPA - approximately 465 mg) and docosahexaenoic acid (DHA - approximately 375 mg).

Hmmm... the major difference is that LOVAZA contains more EPA and DHA than does the Member's Mark OTC version (465 mg of EPA and 375 mg of DHA vs 300 mg of EPA+DHA, respectively).  That's about 2.8X more, which means I would have to take 11 MM softgels per day to equal 4 LOVAZA sofgels (the LOVAZA Web site says "It could take up to 14 capsules per day of an omega-3 supplement to provide the same amount of active ingredients proven to lower very high triglycerides"). My 400 MM softgels would then last me only 1 month or so. That raises my monthly cost to about $18. Bummer!

But wait! What if I were prescribed LOVAZA? How much would it cost me? I'm willing to bet that my insurance company might balk and make the co-pay very high -- say $25 -- or insist on substituting an OTC equivalent, even it means I have to take more pills per day.

So, LOVAZA is likely to cost me about 38% more than Member's Mark Omega-3, but be more convenient because I only have to take 4 of them per day. Note: GSK offers a savings card that allows me to save up to $20† off each of my next 12 refills of LOVAZA. I've tried to find the footnote referenced by that (†) symbol, but can't seem to find it on the Web site. My old eyes may not be good enough. Besides, I probably don't qualify for the full $20 discount -- I never win anything!

My prediction is that LOVAZA is not going to be popular with people like me -- older men with high triglycerides. First, I hate refilling prescriptions and if you think I am going to carry around ANOTHER card in my wallet, you're crazy! Secondly, I am already pissed off that as soon as Abbott came out with its industrial-strength Rx version of NIACIN in combination with something else (I forget exactly what), I can no longer find the right kind of OTC niacin in CVS as I used to. I suspect that CVS took it off the shelf in order to sell Abbott's Rx version (previously, the CVS pharmacist recommended the OTC version, now he is silent about it).

I would love to have been part of the focus group that GSK studied before it began marketing LOVAZA. You did have a focus group, didn't you?

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Afterthought:


Why Did the FDA Approve LOVAZA In the First Place?

Nevermind that this is a "me-too" product that has no business being an Rx drug because there are so many OTC equivalents out there. It is also of dubious value because the data supporting its effectiveness (vs. placebo) is questionable. Here's a table from the prescribing information relating to adverse events:


Note the N values: 226 and 228! If these are the number of patients in the clinical trial, as I suspect they are, then the trial did not include enough patients to prove anything, let alone effectiveness! I am certain you cannot get from 228 data points any significant results that rise above the level of pure chance!

21 comments:

  1. Anonymous10:41 AM

    The focus group was people who love to get prescriptions and talk about how many pills they have to take. These are the same people who will tell you fish oil would never help them, because they are too sick and/or "complicated". Or they don't believe in snake oil/alternative med/woo. Lovaza, on the other hand, will be a miracle drug for them. Because, after all, it is a drug, right? It has to be, if their doctor prescribed it for them.

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  2. Lovaza exists as the most highly concentrated ethyl ester form of Omega-3. In that regard, it is highly toxic (see side effect profile) and thus needs a prescription. This is a great business model but a poor therapy. The side effects result from the release of alcohol which happens when the ethyl ester is converted back to a triglyceride form in the body which is the ONLY way Omega-3s can get into the bloodstream. Remember THERE ARE NO ETHYL ESTER FISH IN THE SEAS. The best way to get Omega-3s safely and therapeuticly is in triglyceride form.

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    Replies
    1. How much ethanol do you think enters the bloodstream when the ester is hydrolysed, and how quickly? Are we talking a drop or two over the course of 90 minutes? Less?

      Think about it - if the body can naturally metabolize the triglyceride, then microbes can too. The ethyl ester is there to keep you from administering a drug with a few live C. botulinum spores in it.

      I'm totally sure taking 11 grams of low density (high volume!) fish oil per day for the rest of your life isn't a disgusting proposition. Patients will TOTALLY comply 100%. And that extra mercury?

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  3. According to the Lovaza package insert, in a clinical study (of only 42 patients in each of the Lovaza and placebo groups) the drug lowered serum triglycerides by about 45% in the Lovaza group from a baseline of 816 mg/dL, meaning that the TG was still quite elevated even on drug (450 mg/dL). Even more concerning is that it raised LDL cholesterol by almost 45% from a baseline of 89 mg/dL, presumably up to about 129 mg/dL. It did increase HDL by 9% - from a very terrible 22 mg/dL. Fortunately, when combined with 40 mg of simvastatin, the drug did not affect LDL levels, and HDL went up a little bit.

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  4. Anonymous1:16 PM

    There is a difference in how Lovaza is manufactured compared to dietary supplements. The latter is a food product with little control on pesticides, PCBs & dioxins, mercury and all the other wonderful stuff which is in the ocean. If one takes 11 fish oil capsules per day, the fishy smell will limit the duration of administration which is probably good news since otherwise the toxic contaminants may accumulate too much.

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  5. Manufacturing and eliminating "fishy smell" is not part of my definition of drug industry innovation.

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  6. Anonymous8:09 PM

    These comments are ridiculous. How many long-term, prospective, randomized, multi-center, placebo-controlled trials have been conducted with fish oil in the form of triglycerides? The short answer is zero. Lovaza has been extensively studied in more trials than are included in the prescribing label.

    Secondly to Dr. Michael Gross, I have no clue why you would consider Lovaza to be "toxic." Any side effects that occured were obviously not serious. The profile listed above is an adverse event profile which reports what the patient experienced, which may or may not be caused by the product. This is different from side effects.

    Thirdly to Daniel, when you mention the increase in LDL-C is concerning it is clear you understand very little about lipoprotien metabolism. Patients with very high triglycerides have an altered distribution of triglycerides and cholesterol within the lipoprotein particle. This means patients with very high triglycerides will almost always have a low LDL-C value to begin with. However, this is a reading that provides very little value because many of the cholesterol esters are actually hiding in elevated VLDL-C. When the very high triglycerides are lowered (by any product), lipid metabolism is restored to a more normal level and the distribution of cholesterol and triglycerides is redistributed, thus VLDL-C will drop and LDL-C may or may not increase. If it does increase it is irrelevent because the atherogenic particles were there to begin with, just not reported under LDL-C. A better predictor of risk is non-HDL-C or even apoB which comprises all of the atherogenic (bad) particles. If you read the prescribing information Lovaza decreases non-HDL-C.

    Lastly to John: There are zero, yes ZERO over-the-counter omega-3 products. Over-the-counter (OTC) infers the FDA has approved the product and can be sold over-the-counter without a prescription. On the contrary, all fish oil products besides Lovaza are actually regulated as dietary supplements and therefore they must contain a food label. Physicians treat patients with very high triglycerides more and more these days and having another option besides fibrates (which have not proven to reduce death) is a positive thing for patients.

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  7. Anonymous12:18 PM

    I like the latest counter to all statements. In particular the response to Dr. Gross. It seems a lot of doctors are being brain-washed to the "it must be the triglyceride form" train of thought even though the only Omega3 studies I found published through PubMed- the National Institutes of Health- were completed using ethyl esters. That being said, then the only proven, acceptable pharmaceutical form would have to be ethyl esters.
    As a side note, it is a shame that the general public really does not know how to read a label. If they see 1000mg fish oil, they think that they have it covered. The key is, what amount of that oil is EPA/DHA? You may have 1000mg fish oil but less than 500mg EPA/DHA combined per dosage.
    One thing I do need to point out is that there are some high quality, molecular distilled, concentrated, pharmaceutical grade Omega3's on the market. You may not be able to pick them up at your local Wal-Mart but I know that they are out there. I take one but I have to call the company to order. Remember, whatever product you are looking at-do your homework.

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  8. I don't see any logic to produce a drug with little improvements, mee-too drug as you said.

    That drug has to get FDA approval and after that will be considered as brand drug which, ostensibly, will be of high cost. Further more it will need prescription to buy.

    Where as drug, little inferior, is available at much lower price and without prescription.

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  9. Anonymous4:28 PM

    Having read all your comments, I'm still in the dark. I questioned the doctor when he prescribed it, my question was, "What is the difference between Lovaza @ 1 gram dose and fish oil gel-caps @ 1000 milligrams?", he blurted out some nonsense about purity and suggested I talk to the pharmacist. I did as he suggested and the pharmacist said, "talk to your doctor". What gives? I don't have insurance and the retail price for this fish oil drug is going to run me $205.99 (120 caps @ 4 per day) There should be a law against this kind of theft!

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  10. My doctor prescribed Lovazafor me. With my insurance the copay was $25.00 per month. I found a website, if I find it again I'll post the link, where someone compared Lovaza to other brands. It turns out that the Rite Aid brand of Fish Oil, which can be purchased for $20.00+ a bottle of 500 capsules provides 360 EPA and 240 DHA per two capsules as opposed to 465 EPA and 375 DHA per one capsule of Lovaza. Even if you took five or six capsules per day of the Rite Aid Brand you come out ahead. I think its a no brainer.

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  11. Anonymous2:51 PM

    @ Dr. Michael Gross - yes, TG forms are initially better absorbed, but research shows that after a couple of days, there is no difference between TG and EE. And 'toxic'? Really? This might be the wrong crowd to scare.

    @condundrum - cost-wise, supplements are clearly a bargain, assuming you've checked out the quality (not sure how one does that.) I'm a nutritionist and the problem with retail fish oil is that you have to tell people to take half dozen or more pills a day. At that kind of dosage, the compliance is ridiculously low. If you find the website you mention, please post. I've only seen this so far: http://www.omegavia.com/lovaza-vs-pharmaceutical-grade-fish-oil/

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  12. Hmmm, if Mr. Anonymous who thinks these comments are stupid is so sure of him/herself, then why be anonymous? The truth is, there are other omega-3 products on the market that do go through a purifying process similar to LOVAZA. Also, many have EPA/DHA counts almost as high per capsule as LOVAZA, so you will only need to take 2-4 capsules per day. "Carlson Elite" fish oil capsules contain 400 mg of EPA and 300 mg of DHA per capsule and it can be ordered on many sites on the internet for $30/180 capsules. Another thought, one liquid form of fish oil I looked at stated it had 825 mg of EPA and 550 mg of DHA per tablespoon - so if you can drink that down you really don't need several capsules per day. It all comes down to your health insurance, really. If you have a really low co-pay, then LOVAZA may be cheaper for you to purchase then regular fish oil supplements. But if your insurance doesn't cover LOVAZA - and many companies don't - than finding an affordable fish oil supplement may make more sense. Either way, by taking fish oil supplements and following a low-fat/low-carb diet, your triglycerides will go down.

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  13. Anonymous10:00 PM

    My doc told me about it when I tested high for total triglycerides too. I told him that I'd rather just try the fish oil supplements first. After some research I settled on GNC triple strength fish oil. it has 647 mg of EPA and 253 mg of DHA in a 1200 mg pill. I take 3 a day for a total of 2700 mg of omega 3's. I've only been taking it for about a month, so I haven't had my triglycerides tested again yet, but I think I'm still ahead in the cash department.

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  14. Anonymous2:58 AM

    FYI re: niacin. The form of niacin on store shelves is one of two types, either "immediate release," which can cause extreme flushing reactions and disrupted levels of things like uric acid; or "sustained-release," which has no medical benefit and is toxic to the liver. The prescription drug by Abbott (through acquisition of inventor Kos) is a sophisticated delivery system that maintains medical benefit while minimizing the side effects of original IR niacin. It has been available for years in combination with the original statin drug, lovastatin (formerly Mevacor) and recently was also combined with simvastatin (Zocor) once it, too, lost patent protection and went generic.

    Many forms of non-prescription niacin are actually health hazards, and you should applaud drug stores for taking them off the shelves. FYI, it's distressing to see you inappropriately use the term "OTC" for non-prescription niacin. "Over the Counter" is a term for FDA-approved medications that previously used to require a prescription but have now been cleared for sale without a prescription. OTC products have data demonstrating efficacy and safety. There is *NO* such form of niacin, and someone offering a blog on pharmaceutical medications should make it his business to research, understand, and properly utilize such terminology.

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  15. Anonymous3:07 AM

    After considerable research and examination of the label for LOVAZA, I also selected the GNC brand. It actually has slightly more active ingredients (EPA/DHA), and in what some experts describe as a more favorable ratio: the body can convert EPA to DHA more easily; DHA does not easily convert to EPA. So these experts advise a 2-to-1 ratio, providing more "spare" EPA in case the body's needs fluctuate, so that the bio-conversion can take place if necessary. (I was always curious why LOVAZA didn't offer this ratio.) Now, unfortunately, I'm concerned about publicized claims (and a lawsuit in California) raising concerns about PCBs and dioxin. When I examined the published results, however, the GNC product named was a "Cod Liver Oil" formulation, and not the "Triple-Strength" product. My understanding is that the same "molecular distillation" process that makes the active ingredients more concentrated also removes impurities. Passing the oil through three times is more expensive but produces a more-pure product, according to what I've been told. Now I'm not sure whom to believe. I'd like to see test results specifically on GNC Triple-Strength. If it passes muster, it would seem to be the best product on the market in terms of bang for the buck. Thanks for the great discussion.

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  16. Anonymous3:17 PM

    I take 4 grams of lovasa a day and im now nearly ready to quit it ...why??? because Id rather die from high triglicerides than smell like and smell fish all the time!

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  17. Yes, be careful using Lovaza if you're concerned about your LDL cholesterol and one would be better off with a niacin tablet; niacinaminde doesn't cause the flushing.

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  18. Anonymous8:32 PM

    My doctor prescribed lovaza for my husband, but my Naturopath ordered me a fish oil with 1050mg of EPA and 150mg of DHA/ teaspoon! :-D

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  19. Mr. Q.3:50 AM

    My doctor prescribed lovaza for my wife, but our insurance will not pay for it.Therefore I paid full price $222.34 only one time in 6mo.s because with only one income now i can't buy all of my wife's meds. I feel bad about it and upset for her health.I got on the computa to fix it or help me with the prob. now i see this is a prob.not just for me but i need help.

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  20. Just eat a can of sardines every day. Problem over.

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