#PoliticalSpeak: the not so BigPharma Alternative – sorry we have let you down

We do not have enough hours, or energy, to reignite our BigPharma Alternative. #PoliticalSpeak #MSBlog

Impact when you don’t expect, or deserve, to have one. I received the following email from a PhD researcher earlier this week:

Dear Prof. Giovannoni,

Your article about repurposing in ‘Multiple Sclerosis and Related Disorders’ has caught my attention.

I am a ….. researcher at the ……. and I am doing research about drug repurposing in oncology. More specifically, I am focusing on the regulation, the intellectual property right strategies, and the economic implications of drug repurposing.

I am working in close collaboration with the Anticancer Fund, a Belgian non-profit organization that is currently funding several clinical trials investigating off-patent repurposed drugs in cancer patients.

Similar as to what is described in your article, we have encountered several hurdles in getting the repurposed drugs to the patients. Please find attached our policy brief listing these hurdles and proposed action items for regulators and policy makers.

I think the proposed movement to support the “Big Pharma Alternative” as described in your article is inspiring and I was wondering whether there is any progress in the field of multiple sclerosis with regard to drug repurposing?

Thank you for your time, I look forward to hearing from you….

Sadly, I have to respond to him that the BigPharma Alternative has floundered. We have only so many hours in a day and when the repurposing, or off-patent, drug bill was filibustered out of the house of commons and we we received a stern response from George Freeman, the then Parliamentary Undersecretary of State for Life Sciences, stating that there were no hurdles for prescribing off-label we lost steam. What George Freeman was saying that Pharma, in particular Big Pharma, is such a big part of or knowledge economy that we don’t want to kill the goose that lays the golden eggs. In other words let Pharma innovate and make money, we will pay them, tax them and we will all live happily ever after. What this attitude doesn’t address is the difficulty people have when they live in resource-poor environments, or are part of healthcare systems that require individuals to co-pay. Two thirds of personal bankruptcies in the US are triggered by ill-health. The article below from an American lawyer highlights the other side of the story, or the underbelly of Big Pharma; i.e. their predatory behaviour to milk the system. This is something we can’t ignore and it is very prevalent in the MS space. 

Can we revive our BigPharma Alternative? I am not so sure. We will continue to promote our Barts-MS Essential Off-Label DMT list for use in resource-poor environments and will provide our off-label treatment protocols to anybody who wants to use them. However, we don’t have the energy or resources to take these big issue on by ourselves; the sad thing is the politicians and lobbyists seem to have won. Just may be if the health policy unit at our University had supported us we would have had a chance of building some momentum, but Professor Allyson Pollock, who has now left our University, was adamant that she thought what we were doing was wrong. The good news is that the MS International Federation, or MSIF, has agreed to carry the baton when it comes to promoting off-label DMTs in resource poor environments; at least we have some help on this front. This is the battle we are prepared to fight, with a little, or a lot of, help from our friends. 

Giovannoni et al. The problem with repurposing: Is there really an alternative to Big Pharma for developing new drugs for multiple sclerosis? Mult Scler Relat Disord. 2015 Jan;4(1):3-5.

If it is not feasible to develop licensed drugs to the stage that they can actually be prescribed for a new indication, can we justify, either ethically or economically, the undertaking of proof-of-concept studies using off-patent medications? Without a financial incentive it is very difficult to repurpose off patent drugs for a new indication. Therefore, we need a political solution to allow the repurposing of off-patent drugs by other stakeholders or Big Pharma.

Levy MS. Big Pharma Monopoly: Why Consumers Keep Landing on “Park Place” and How the Game is Rigged. Am Univ Law Rev. 2016;66(1):247-303.

Now, more than ever before, pharmacologists are contributing medical advances to confront ravaging disease. They are developing drugs to mitigate the effects of Alzheimer’s, HIV, multiple sclerosis, and various forms of cancer. To capitalize on the opportunity, brand-name pharmaceutical firms are patenting these drugs, consequently guarding formulas and, with it, profits. Patents grant brand-name firms market exclusivity, which essentially allows them to set their own prices. Even though brand-name firms are investing some of their capital to cultivate new drugs, they also are enjoying gigantic revenue streams, absurd profit margins, and seemingly unfettered control of their respective markets. Consequently, sick patients are unable to afford their medication; high prices are bankrupting consumers in the absence of reasonably-priced generic alternatives. Despite the fact that generic drugs contain identical ingredients, cure the same symptoms, and cost 70% less, brand-name drugs persistently dominate their generic counterparts. Indeed, brand-name firms are improperly preventing generic market entry. Without generic competition, no watchdog exists to curb big pharma’s prohibitive prices. Despite the Supreme Court’s fleeting fix in FTC v. Actavis, which condemned reverse payment settlements that precluded competition, brand-name firms are employing other tactics predatorily to extend their market exclusivity and charge consumers unaffordable prices. To prevent brand-name abuse and help infirm patients afford their medication, this Comment proposes that courts apply federal antitrust law to brand-name firms that attempt to monopolize a pharmaceutical market through anticompetitive means, particularly by abusing Risk Evaluation & Mitigation Strategies (REMS) and by “product hopping.” To combat exclusionary conduct, courts should mirror the “rule of reason” framework set forth in Actavis and apply an “enhanced” version specifically tailored to the pharmaceutical industry, giving stronger credence to generic challengers. In addition to finding brand-name tactics exclusionary, this Comment also proposes that courts adopt a bright-line rule prohibiting brand-name firms from exploiting the “legitimate business” defense to immunize their destructive conduct. The current framework perpetuates abuse and grants brand-name firms ostensibly indefinite monopolies. Analyzing brand-name defensive tactics under federal antitrust law would facilitate generic market entry and consequently moderate drug prices. Even after sacrificing their entire financial portfolios, patients are still unable to afford their medication. This Comment interprets Actavis as prohibiting the “legitimate business” defense and provides a remedy to deserving consumers by preventing REMS abuse and product hopping, fostering generic competition, and tempering excessive drug prices.

27 thoughts on “#PoliticalSpeak: the not so BigPharma Alternative – sorry we have let you down”

  1. I am afraid that in the end public-funded healthcare systems are going to end up in the "Park Place", paying those prices is not sustainable in the long run. Cancer drugs can cost £100,000 a per patient/year, Lemtrada costs something like $100,000 for the first year in the US. Oh, wasn't it the same as Campath? 🙂 Any guesses how much Ocrevus is going to be when it becomes available? In the end even the rich countries will not be able to afford those treatments.

  2. or maybe it is a self-regulating mechanism – the drugs cost as much as they do because it is the public healthcare systems and insurance companies that have to pick up the bill. Nobody(except maybe a few Trumps 🙂 could afford to pay those prices as an out-of-pocket expense. Then the drugs would have to be priced more accessibly – like they were before : people went to the pharmacy and you paid for their prescriptions. Not in hundreds of thousands of pounds/dollars etc.

  3. There is no appetite for repurposing drugs for RRMS, this is the sorry of state of affairs as far as the MSIF and MS Societies goes. Can they do it for PP/SPMS?

  4. I have a really silly question to MD … does experimental MS in rodents get worse if you feed them cow's milk? Or even better … feed them cheese made from cow's milk( high in milk protein and in salt). That would be a blockbuster experiment ( I suggest using cheddar, it would certainly make headlines in the pop media like Nature :-).It may even explain the paradox of why there is more MS in Europe and America and less in countries that are further from the Equator (less milk consumed).(however, the Japanese do use a lot of salt in soy sauces, so the salt is a red herring here 🙂

    1. If my memory serves me well, we did once feed milk to mice when were were seeing if we could prevent weight loss and dehydration and it had no effect.However, we can't feed them cheese as it is not designed for mice in terms of nutrients…the block buster experiment would perhaps end in the papers but because the RSPCA has got us busted for animal abuse:-(Maybe we should report on the observation that a certain drug given to spastic EAE mice made them ejaculate. If MD2 had taken pictures it would have gone straight into Mouse Pawn (spelt wrong) weekly. As you say does autoimmunity occur more often in regions with alot of salt in the diet.

    2. Ok, so cheese is a good enough food for me, but is not a suitable food for mice :-). But wait a minute, why is prevalence of MS in Japan 2 to 7 per 100,000 and over 200 per 100,000 where I live? What do the Japanese do right that I do wrong?

    3. Cats eat catfood and it's good for them but I wouldn't recommend it as a diet for you. A well balanced diet for all.What do Japanese do?They have Japanese parents and live in Japan. They have different climates, lifestyles and genetics. The risk factors that we know about have small influences on risk, so when we do trials with vitamin D and salt should we expect big influences? I doubt it

    4. Re: "…are the rates of EBV infection different in Japan?"Unlikely. What this study shows is that vertical transmission n childhood is reduced and that you are more likely to acquire EBV later in life and get infectious mono. This is the real change.

    5. Is EBV early in life somehow protecting against clinical MS? if the Japanese get EBV earlier and have much lower prevalence of MS than the caucasians. Assuming, of course, that EBV has some role to play in the development of MS.

  5. The climate in Japan is mostly temperate so it does not explain a thing…When people move from low-endemic areas for MS to high endemic areas they get higher risk of MS ( so it is not all about the Japanese parents/genetics). What if your memory cells are cells reacting to something in the diet, for example milk proteins ( after all, has anybody ever seen an ape sucking on a cow (how ridiculous!!!) – so how natural and balanced is our European diet???)

    1. 36 degrees North Japan, 55 degrees North UK, Spain 40 degrees North. Florida 31N. Sunlight the same?As we have said numerous times the environment has a major impact.A yes the next MS risk paper Cows Milk and MS:-(Or have we been there alreadyAntibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis.Guggenmos J, Schubart AS, Ogg S, Andersson M, Olsson T, Mather IH, Linington C.J Immunol. 2004 Jan 1;172(1):661-8.

  6. And it is not salt because soy sauce is 16,9 g salt /100 ml (just checked 🙂 – the Japs would be at high risk 🙂

    1. wouldn't you think this aspect would be addressed in the papers?Did you read DrK on Twitter this weekend talking about Dr. Hagler this weeekend.

    1. I love this paper :-D. The most important thing – the dose/or the magnitude of intervention is not easy to find in the codswallop. Where did you find how much the mice fed "ad libitum" actually consumed of water/chow laced with salt? I can't easily see it, only the salt concentrations in chow/fluid.

    2. I work with humans, not mice… so I probably would not think of the micro dinner portion sizes and adjusting of the dose for mouse. But then again people in the mouse lab should know better."All Experimentation was performed according to the German animal protection law". I do not know what that law states, but it certainly must say something about not conducting meaningless experiments on animals?

    3. Anon 11.02 (I wish people would use a name or pseudonym if you prefer).How I did it was I got the figures for how much on average food and drink a mouse consumes (for the mouse strain C57bl/6 in this case)from a research publication. Given the salt concentrations used in the experiment, I calculated how much salt the mice would be taking on a mg/kg basis, then scaled up to how much salt an "average" human would have to consume. I guess my figures are correct (we checked a few times as I was stunned at what it works out to) as they haven't been challenged by the authors.

    4. BTW the paper has an Altmetric score of 421, which tells you all you need to know about this measure of a paper's worth.

    5. @MD2, I could not believe it so I calculated it from your "daily portion sizes", and yes it is 0,6 kg salt/day if I wanted to try this experiment in patients of average weight. Which make this experiment totally meaningless. And then one can wonder if the whole thing is fabricated because what animal could possibly eat that amount of salt and survive? (or maybe the mice went anorectic in the end as they could not face yet another salty dinner?)And the worst thing is… if you did not point the problem out I would not blink twice reading the paper, good journal and all that :-). Goes to show. :-)))))) Not the first piece of … ever published and not the last either.

    6. I couldn't believe it either, I went back and redid the calculations several times and asked MD to independently check my workings. As you say, most readers would not be aware of this, more disturbingly neither were the referees, who should hang their heads in shame. Nature don't care, they got lots of impact/publicity. This paper is merely the tip of a very large iceberg and people wonder why we're cynical.

    7. It is Nature's editor who sent it to wrong reviewers. If you ask somebody who does not work with mice than it is all very pretty and scientific looking data. But the problem actually started in Germany – somebody blinked and approved totally silly animal study to go ahead (shame, blame, shame on university authorities there!). Unethical torturing of animals that does not give any meaningful result, because it is nonsense already in the planning phase. MD2 could you poke 2 studies and find their fatal flaws (that I do not see because I am not a lab scientist): https://www.ncbi.nlm.nih.gov/pubmed/14688379https://www.ncbi.nlm.nih.gov/pubmed/11254737

    8. I suspect, once the Nature referees saw who the senior author was, it was nodded through. Happens again and again with the big names in the field.

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