a couple more drug company shenanigans

 the NY Times had another article by Rebecca Robbins on drug company shenanigans, this one on the delayed release of a superior form of tenofovir in the pursuit of profit (see https://www.nytimes.com/2023/07/22/business/gilead-hiv-drug-tenofovir.html?smid=nytcore-ios-share&referringSource=articleShare ).

 

Details:

-- Gilead Sciences developed tenofovir disoproxyl fumarate (TDF), which became available in 2001 and was a game-changer for HIV treatment, the single best med at that time. it also was an excellent treatment for chronic hepatitis B infection

-- unfortunately, there were a few important adverse effects well-known at the time: kidney failure and osteoporosis

-- tenofovir alafenamide (TAF) was initially approved in 2016, as an upgrade, with similar benefits to TDF but significantly fewer renal or bone problems (TAF has much lower plasma concentrations than TDF)

  

But:

-- in 2004, Gilead was developing a "next generation prodrug of tenofovir", noting that this "may provide an additional four years of market exclusivity compared to TDF", with roughly "$325MM in yearly Net Sales", though publicly stating that they had decided to stop pursuing the new HIV drug (TAF) since Gilead "does not [my bold] believe it has a profile that differentiates it to an extent that supports its continued development" (all quotes here are from their internal documents, as referenced by the NY Times, with my clarifications in brackets)

    -- however, another 2004 document from Gilead did show they were in fact pursuing this prodrug (GS-7340, now called TAF)

    -- another internal document revealed their perhaps real fear: GS-7340 (TAF) “would ultimately cannibalize Viread [TDF] regardless of its efficacy and safety profile. One reason for continuing/restarting development [of TAF] would be to obtain patent extension”

    -- and, they noted that "at the doses used, TAF produced lower systemic exposure to tenofovir than Viread [their trade name for TDF] which could translate into reduced potential for long-term toxicity [ie, renal or bone mineral density]"

    -- TDF was set to lose its patent protection in 2017

    -- another internal memo commented about the sale and marketing of TAF: “a 2015 commercial launch in the US and EU simultaneously; generic competition launches [in] 2017”

        -- so, Gilead resurrected TAF in 2010 in anticipation of a 2015 release, then promoting it as being “safer for kidneys and bones than the original” (which is true), despite its initial memo to the contrary

        -- Gilead decided to delay the new TAF since "it risked competing with the company's existing, patent-protected formulation", and ultimately delayed its release until shortly before the existing patent expired, and allowing Gilead another 10 years of a highly-priced tenofovir

        -- the timing of the release of TAF while TDF still had a year of patent-protection allowed the company to promote switching patients to this improved tenofovir before generic TDF became available.

    -- this delay effectively extended the patent for the best tenofovir product until 2031, a "patent extension strategy", though there is also a pharmaceutical industry name for this: “product hopping”

    -- and, of course, this delaying strategy was "potentially worth billions of dollars"

-- the current price for TAF as a single agent is $26,000 annually, vs generic TDF at $400/year

-- and TAF, typically prescribed in combination with other HIV drugs, is in ½ of all HIV treatment regimens (and TAF is often prescribed as a lone agent for chronic hepatitis B)

    -- according to the market research firm Ipsos, nearly half a million HIV patients in the US in 2021 were taking Gilead products containing TAF

 

Commentary:

-- needless to say (but i will still write it): this approach by Gilead utilized strategic timing to maximize their profits, though it was remarkably unethical and put many patients unnecessarily (and unconscionably) at risk for significant kidney and bone disease

-- but perhaps their chickens are coming home to roost: there are now state and federal lawsuits where 26,000 patients are suing Gilead for unnecessarily exposing them to kidney and bone problems

 

The above Gilead example refers to counteracting potential internal competition for important drugs. The following is an example of trying to prevent external competition (thanks to Paul Susman for bringing this to my attention), see https://www.twn.my/title2/health.info/2023/hi230705.htm

 

Details:

-- Palbociclib (trade name “Ibrance”) by Pfizer was approved by the FDA in 2016 to treat HR+,HER2- metastatic breast cancer, expanded in 2017 to be first-line therapy

-- Palbociclib has generated $5.12 billion to Pfizer for its domestic and global sales, and is Pfizer's top selling oncologic med

-- several companies have introduced generic versions of Palbociclib, at a price tag of $54.84 per month, a tad below the $1157/month for the Pfizer drug

-- the patent for this med in India ended in January 2023

 

-- as a background here,

    -- international law regarding Free Trade Agreements (FTAs) internationally are a bit complex:

        -- many provisions go beyond the Trade-related Aspects of Intellectal Property Rights (TRIPS) Agreement administerd by the World Health Organization, most having Patent Term Extension and Data Exclusivity (especially in the US, EU, UK, Iceland, Liechtenstein, Norway and Switzerland)

        -- though India was required to amend or enact its patent laws to conform to TRIPS, they were able to balance these changes to mitigate the health impact of drug patents and improve affordability of the meds: India avoided mirroring the US patent system in order to allow for affordable meds domestically and globally, decreasing drug company patents that limited generics and thereby increased their lucrative global profits

        -- as a result, Indian patients are able to access Palbociclib at the cheap generic prices, though the med did receive a 4 year patent extension in the US until 5March 2027, and Prizer is trying to block generic versions from entering the US market until then

  

Commentary:

-- the big issue here is that the Pfizer pill would have been unaffordable for thousands of breast cancer patients in India. And this is true for many countries internationally, denying many, many people from a potentially life-saving med

-- in India, most of the health care expenses are borne by the government or by the patients themselves: in 2019-20, 52% of health care expenditures were out-of-pocket

-- the table in the document above lists several other similar oncology meds that have been granted patent extensions in the US, along with the huge differences in cost between the generics and brand-named meds (including pertuzumab, atezolizumab, ado-trastuzumab, brentuximab, and ribociclib)

-- the US has the highest pharmaceutical cost per capita ($1443 vs a mean of $749 in other resource-rich countries: http://gmodestmedblogs.blogspot.com/2018/03/health-care-spending-and-outcomes-in-us.html ), particularly an issue since a huge segment of poor Americans (esp in the rural South) are without health insurance and many more without adequate prescription coverage

 

So, the issues here:

-- it seems that drug companies are able to set very high prices for new meds, and they are often quite successful in extending their patents beyond the usual interval

    -- it is also notable that the FDA requires drug studies to be listed in the website clinicaltrials.gov, so that there would be public access to all trials (including those with negative results that might not be published). BUT, there is very poor drug company adherence (see http://gmodestmedblogs.blogspot.com/2013/11/more-drug-company-shenanigans.html ), and almost no regulation at all for most medical devices (http://gmodestmedblogs.blogspot.com/2015/08/regulation-of-medical-devices.html )

-- for a review of drug company price-setting, focusing on the mechanisms they use to inflate the R&D costs, “justifying” the exorbitant prices of meds, see https://www.bmj.com/content/345/bmj.e4348, doi: 10.1136/bmj.e4348

 

-- for the very many blogs over the years about drug company shenanigans/malfeasance/greed, see http://gmodestmedblogs.blogspot.com/search?q=drug+company+shenanigans

-- so, bottom lines for the international issue:

    -- many high-priced drugs get extensions of their patents in the US, leading to:

        -- extraordinary prices and drug company profits, typically for several years

        -- maintaining very high prices in the US, a very large drain on the costs of health care in the US leading to high insurance costs for those with private insurance, and very high public costs for those with government-funded programs (eg Medicare part D: per enrollee spending on prescription meds averages $2700 per year (https://www.cbo.gov/publication/57772 . A 2016 blog noted the huge increase in Medicare part D spending, from $51 billion in 2006 to $137 billion in 2015: http://gmodestmedblogs.blogspot.com/2016/06/drug-company-shenanigans-blogs-continue.html ). and this translates to high taxes on the general population to pay for this (sidestepped as always for the obscenely rich), and, for a large swath of people with no or grossly inadequate health care insurance, making important drugs largely inaccessible

        -- and the high costs for many patented drugs are also quite high in much of the world (some, like the UK, have been able to negotiate better deals with drug companies, one of the benefits of their single-payer system with the ability to negotiate prices….)

 

-- and bottom lines nationally:

    -- the cost of medications is overwhelming our health care system, which is a financial burden on tax payers and leads to some in congress to regularly fight to decrease health care spending (leading to even less access to care)

    -- drug companies, per many of the prior blogs, are “making out like bandits”, “laughing all the way to the bank”, etc etc etc

       -- this is particularly easy in the US, since we do not have a coherent health care system (eg single-payer), or one that allows for significant bargaining with drug companies (esp Medicare: per George W Bush’s establishment of Medicare D, Medicare is legally unable to negotiate drug prices (see https://www.nytimes.com/2023/07/23/us/politics/medicare-drug-price-negotiations-lawsuits.html )

 

geoff

-----------------------------------

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@bidmc.harvard.edu

  

to get access to all of the blogs:

 

 go to http://gmodestmedblogs.blogspot.com/ to see the blogs in reverse chronological order

  -- click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category​

  -- or you can just click on the magnifying glass on top right, then type in a name in the search box and get all the blogs with that name in them

 

if you would like to see the articles in this blog, please email me. 

 

please feel free to circulate this to others. also, if you send me their emails (gmodest@bidmc.harvard.edu), i can add them to the list