Drug company shenanigans: narcolepsy drug

I have not done a blog for a long time on drug company shenanigans. So it is my great pleasure to bring up a brand-new drug company approach to garner huge amounts of money (see https://www.nytimes.com/2023/02/28/business/jazz-narcolepsy-avadel-patents.html?smid=nytcore-ios-share&referringSource=articleShare ). Based on an article by Rebecca Robbins of the New York Times, who has written several articles on drug company excesses

 

As background, this will be my 42^nd such blog: for the array, see https://bucommunitymed.wpengine.com/page/4/?s=drug+company+shenanigans

 

The drug company approach this time to extending their patents has a few “interesting” angles:

-- this is a medication manufactured by Jazz Pharmaceuticals to treat narcolepsy: there are 2 versions: Xyrem and Xywav (Xywav has less sodium, so is marketed to those who should be on a low sodium diet). These meds are basically derivatives of gammahydroxybutyric acid (GHB)

    -- the drug actually has a pretty “unusual” history: it has been used as a date rape drug!!! As a result, the feds required it to have safety precautions, so it has a single pharmacy nationally that sends the meds directly to the patient

-- these meds produce gigantic profits (>$13B, ie billion, since 2005, 58% of Jazz’s revenue in 2021; Medicare pays Jazz hundreds of millions of dollars annually for it), with the highest dose costing >$200K, ie thousand, per year and is 19 times more expensive now than it was in 2007…)

--BUT, there now is competition:

    -- the new angle to undercut the certification of a competing med: focus on the FDA’s required safety program, which Jazz targeted and patented

    -- and, per Rebecca Robbins, under “an obscure federal rule” (https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/patent-certifications-and-suitability-petitions ), “if a rival contested one of the patents in certain circumstances, federal regulators would be barred for” … “at least 30 months” … “ from approving that competitor’s product” , though the Federal trade commission and 2 federal courts have subsequently ruled that this rather sleazy approach is illegal. The goal of Jazz here is to make it very difficult for competitors to set up a different but acceptable drug monitoring system (REMS: Risk Evaluation and Mitigation Strategy) that would satisfy the feds

        -- and, even a small delay created by Jazz's ploy will lead to lots more money for Jazz (their REMS patent was set to expire June 17, so the delay would actually be for 12 months, still a huge sum of money…)

        -- and the rival drug leading to this whole issue actually is an improvement: the Jazz ones require twice-dosing (yes: a drug for sleeping requires one to wake up 4 hours later to take the second dose…..), but the competitor (Lumryz) is basically the same med but is only a once-a-night dosing. This drug company petitioned the FDA in 2020 for approval of the med (the FDA did rapidly determine that Lumryz was safe and effective and “tentatively approved” it, the usual initial approval step before the final approval)

 

So, this drug company (Jazz) has found yet another angle to reap huge profits. They have bypassed the typical old-fashioned approaches of prolonging their drug monopoly, ie:

    -- by tinkering with the chemicals involved: the vast majority of new drugs, as of 2018,  introduced a small variant of an old drug that usually did not really add anything useful clinically, but had new marketing and higher prices

    -- playing around with the dosages available: as one of many  examples, Prozac, when it became generic fluoxetine, was repackaged/re-patented as a single 90 mg pill, along with lots of fanfare about the new weekly dosing though not even a slight chemical change.

    -- and there have even been lots of sinister drug company plots, like taking a drug like colchicine that was used eons before the FDA existed, doing a very inexpensive small study to show it was effective for gout, then getting an FDA license for a patent, then charging $6 a pill as opposed to a couple of pennies (see below for more info)

    -- or through their study design: studies are typically designed by the drug companies to achieve the results they want, even with FDA oversight. for example, a study comparing semaglutide vs the new tirzepatide for weight loss, found that tirzepatide was better. But they compared it to semaglutide 1mg instead of the 2.4mg dose used in the semaglutide studies....: see http://gmodestmedblogs.blogspot.com/2021/07/diabetes-and-weight-loss-tirzepatide.html

   -- or by suppressing results from negative trials (which is not just unethical but may be illegal): eg JAMA published a trial of gabapentin for neuropathy and chose a very high dose of gabapentin for the study (perhaps to increase the cost if it were to be used in practice....) and finding benefit. but a subsequent and larger study sponsored by the drug company found no benefit but was never published....

    -- or, another recent New York Times article by Rebecca Robbins, where the remarkably lucrative drug Humira ($50,000 per year per patient) was about to be inundated with an array of rival versions, was able to build “a formidable wall of intellectual property protection and suing would-be competitors before settling with them to delay their product launches until this year”, and this was particularly successful at manipulating the issue of US intellectual property (despite the fact that their patent was over): see https://www.nytimes.com/2023/01/28/business/humira-abbvie-monopoly.html

  

but, it is great that there are people/organizations that are popularizing these drug company shenanigans. The NY Times has been in the forefront of this, as well as STATnews. And the BMJ has been a leader in the medical literature, with an article in 2012 detailing the rather remarkably corrupt basis for pricing new drugs (see drug co research devel bmj2012 in dropbox, or doi: 10.1136/bmj.e4348), the vast majority of which are look-alike remakes of older drugs; and Deborah Cohen’s many articles at the BMJ exposing internal drug company documents showing the need for dose-adjustment of dabigatran (the first direct oral anticoagulant), undercutting their major selling point that it did not need dose monitoring, unlike warfarin (see below)

 

For a sampling of the prior blogs on drug company malfeasance: 

-- From a 2018 blog: http://gmodestmedblogs.blogspot.com/2018/12/generic-drug-prices-skyrocketing.html colchicine has been around since at least the 6th century, had cost a few pennies per pill, but URL Pharma won exclusive FDA approval to sell its brand-name drug at $6/pill. this was based on a really inexpensive study they did of 184 patients who got placebo vs colchicine at higher or lower dose levels, finding not-so-shockingly that colchicine worked. and now this really important and useful drug required a prior approval for many years, and in many of my patients, this approval was denied. i have had several patients with recurrent gout being put on allopurinol but needed colchicine both to treat their gout and prevent recurrences with allopurinol uptitration. the insurance company required me to use the much more toxic NSAIDs and prednisone prior to getting that approval. 

 

And others: 

--  http://gmodestmedblogs.blogspot.com/2018/12/generic-drug-prices-skyrocketing.html: price-fixing of generics for albuterol inhalers, doxycycline and glyburide

-- http://gmodestmedblogs.blogspot.com/2022/01/atrial-fib-apixaban-outperforms.html which provides evidence that rivaroxaban is inferior to apixaban.  both agents have similar half-lives, but rivaroxaban has the huge benefit of being accepted as a once-a-day med despite having the same half-life as apixaban, and rivaroxaban (no doubt as a result of this once-a-day dosing) has both increased bleeding and increased clotting (too much med earlier in the day causing the bleeding, early effect wearing off causing the clotting, as well as a more profound problem when even a single dose is missed). As a further background into the malfeasance related to DOAC development (no doubt spurred on by the potential company windfall):

    -- the use of defective point-of-care INR machines in the rivaroxaban trial, which altered the risk-benefit analysis in its comparison with warfarin (see http://gmodestmedblogs.blogspot.com/2016/02/rivaroxaban-is-it-really-better-than.html for a review of the BMJ article that exposed this) 

     -- another series of articles in the BMJ that exposed pretty blatant drug company malfeasance with regard to dabigatran, the first DOAC: see http://gmodestmedblogs.blogspot.com/2014/07/big-pharma-yet-againagaindabigatran.html and http://gmodestmedblogs.blogspot.com/2014/11/dabagratan-again.html ) 

-- http://gmodestmedblogs.blogspot.com/2016/11/generic-drug-price-variation-for-heart.html the huge generic drug price differences for heart failure meds sold in the same geographic area and independent of the type of pharmacy or local income of the neighborhood 

-- http://gmodestmedblogs.blogspot.com/2015/11/drug-company-shenanigans-this-time-with.html the huge increases in generic drug prices, for really old drugs that used to cost pennies and then up to about 8,000-fold increases

-- http://gmodestmedblogs.blogspot.com/2018/12/high-insulin-cost-leads-to-underuse.html the dramatic patient effects of the profound increases in insulin prices

-- and, lots more blogs ….. (see https://bucommunitymed.wpengine.com/?s=shenanigans)

 

geoff

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