Economics should trump what is actually best for people with MS; i.e. neurologists should prescribe rituximab over the more expensive innovator drugs as it saves their healthcare system money.
“The global Multiple Sclerosis (MS) drugs market generates approximately $22.95 to $29.37 billion annually. This specialized space is heavily dominated by monoclonal antibodies, with Roche’s Ocrevus leading globally at about $7.6 billion in yearly sales.”
Top industry pay packages for recent fiscal years:
- Johnson & Johnson: Joaquin Duato leads the pack, with his compensation jumping to $32.8M.
- Pfizer: Albert Bourla received $27.6M after overseeing recent strategic acquisitions.
- AstraZeneca: Pascal Soriot earned around $23.9M.
C.$30 billion a year revenues from MS therapies, yet not one tackles the real MS (smouldering MS), not one tackles the cause of MS (EBV), and not one reverses damage (remyelination therapy, therapies to promote axonal growth etc.).
As a neurologist who has spent the last 25 years of my life developing new therapies for pwMS, including as GDTL for the ocrelizumab program at Roche, responsible for the design and initiation of the OPERA program, and over the last 12 years, as CMO of 3 biotechnology companies, I can say with confidence that your comments are well considered. Do CEOs of major pharmaceutical companies make too much money? Of course they do. Do their salaries substantially increase the cost of new drugs? No. Not really. I can say with certainty that the funding environment for novel therapies being developed by small, innovative companies has never been worse. This is driven by the chaos in the US government, global economic “interesting times” and loss of willingness to take risk. Drug development (especially in MS) is risky and costly. My current company has an exciting, novel drug with strong, replicated preclinical data demonstrating both remyelinating and synaptic protective properties. Despite having clean Ph1 data, whether we will ever be able to fund even an exploratory Ph2 POC study remains an open question. The bottom line is; if people of the globe want new, innovative therapies for devastating neurodegenerative diseases, at some point they will have to be willing to pay the price.
I agree that pharmaceutical innovation has to be funded and that companies deserve a fair return for genuine breakthroughs. However, I think the issue is more complex than describing countries like the UK as “freeloaders.”
The NHS has a duty to use finite public funds wisely. Every additional pound spent on one medicine is a pound that cannot be spent on cancer care, mental health, community services or other patients. NICE wasn’t created simply to drive down prices, but to ensure that limited NHS resources deliver the greatest overall health benefit.
I also think it’s important to recognise that the current imbalance isn’t solely the result of countries like the UK negotiating lower prices. It is also a consequence of the way the US healthcare system operates and the pricing strategies adopted by pharmaceutical companies, which have historically been able to command much higher prices there. That is a feature of the market, not something imposed by the NHS.
Finally, I don’t think the UK is simply a “freeloader”. British taxpayers already contribute significantly to medical innovation through publicly funded research, universities, the NIHR, clinical trials and the NHS itself. If the global model for funding pharmaceutical innovation is becoming unsustainable, perhaps the answer is a fairer international approach to sharing those costs, rather than expecting publicly funded health systems to pay more at the expense of other essential NHS services.
Something I haven't discussed is that Big Pharma are generally considered a blue-chip investment and is part of almost all private pension fund portfolios. Therefore, reducing their profits and dividends is like cutting your nose off to spite your face. Not to mention that the pharmaceutical industry punches above its weight in terms of its contribution to GDP. The exodus of big pharma from the UK has had a significant macroeconomic impact. The current government, with Patrick Vallance, is trying to row back against the tide. In my opinion, this is too little and probably too late; hence AstraZeneca's and Merck's (US) decisions to scale back or stop their UK investments, respectively.
Its interesting Gavin, I came across a video recently where this very knowledgeable person said Australia is a top destination for big pharma to do trials. I think is was due to favourable regulations, financial incentives and world class hospitals and medical professionals that encourages them to start their phase 1 trials in Australia.
What "global model" for funding pharmaceutical innovation? All I can see is a mish-mash of funding sources, some more reliable than others. It's not like there is some body that is designing fair funding strategies. Private equity is showing its rot at the core, and certainly philanthropy is not anything approaching a panacea, since individual philanthropists are notoriously fickle and can be their own weather systems that can end up wasting brainpower by driving their pet projects down unproductive roads (think Bill Gates and American education)
And at the end of the day, pharmaceutical companies are simply concerned with THEIR bottom line. If pressed hard enough (probably requiring thumb screws), their leadership would drop their already-gossamer fig leaves and admit that money is their ultimate driver and all the rest be damned. They are beholden to their shareholders first and always, and any public good is secondary. They will chase the money, and in a capitalist system, there is no amount of money that is ever, ever enough, meaning people/governments will always come to near-fisticuffs defining what a "fair return" means. And meanwhile our brains are melting.
And here I will simply comment on what the pharmaceutical companies' being able to command higher prices here in the US actually looks like from a vantage point on the ground.
Back in 2018? After being forced out of work by our monster, I had to be on my husband's insurance for a while before my own Medicare disability insurance kicked in (there is an 18 month waiting period - during which you've lost any employer-provided health insurance you may have had, which means if you don't have other sources of health coverage, you are potentially well and truly screwed). His insurance, in an extremely rare - in my experience - incidence of transparency for an insurance company, gave us an end-of-year accounting of all the monies they spent for our care. That year I was on dimethyl fumarate. My husband's insurance, for 12 months, paid $62,000 for that single medication. I can't recall what co-pay I paid per month, I THINK it was in the $60-100 range, but pay monthly I did.
I think as well as the complexities of economics that you have described, there is also the ongoing cost of using a cheaper drug off label if it is less effective. That would suggest that the patient is going to need more support, in the future, to live with their illness because they are more affected by it than if they had been treated with the licensed more effective medication. At some point the lifetime costs as a result of prescribing the cheaper alternative will become more than the lifetime costs of the licensed drug, assuming that the patient lives beyond that switchover point.
At some point, all innovator drugs come off patent and become cheaper. The relatively short patent life on medical innovation is the deal we, the population, make with pharma. We grant them exclusivity for a short period to recoup their investment and make a profit, and then the innovation becomes open for all to use. Allowing off-label prescribing when licensed options exist is reneging on this deal. Governments know this, but as the Americans are paying, who cares? The current US Government cares.
Prof G was discussing using Rituximab rather than ocrelizumab, ofatumumab, and ublituximab. I.e. a cheaper, less effective drug. It wasn't my assumption, it was based on his evidence from Norway and Sweden.
Not that small when you look at the end organ. Brain volume loss on rituximab is probably worse than with interferon beta, compared to ocrelizumab being superior. Don't let relapses and MRI activity blind you.
Not that small if you measure it by brain volume loss or atrophy. It depends on how much you value the neuronal reserve or resilience required for healthy ageing.
It may be very small, but if considered more generally it is another example of hidden future cost to whom? The health system involved? Patients who later realise they didn't get the best treatment. I don't know about you, but I would be cross. I'm lucky, I am fine on Siponimod, the only treatment licensed for SPMS, unlike
In Australia where I live and I've got PPMS there was news in the last few days about Ocrevus, kesimpta and something else not being on the PBS anymore but the PBS folded and it kept those drugs on the PBS. It's A$17000 a bag for the infusion so I can understand the push to not have it on the PBS if another drug like rituximab does a similar result.
Good discussion. Welcome to the states, which are in chaos, as tout le monde knows. The last thing concerning the crazies here is spending money to maintain people with chronic illnesses. Regarding those evergreen patents, interferon beta now has a co-pay of +/- $800. And with Medicare privatized, (which it is, with horrible rules which most citizens do not understand), we are being forced to the cheapest drugs from the worst laboratories (you can look up the labs), even with the most expensive Medicare D policy, which solely covers drugs. The price of drugs has been driven down, however, there is no “donut hole“ relief after paying a ceiling amount. This is pure profit in the pockets of insurance companies from the extortionate policies.. don’t even get me started. I used to represent them.
Roger that, Goldweave. I often pictured two people in a room, each with a phone, just saying no, no and no. What insane country has a clause in medical policies stating “the approval of this blah blah drug/procedure etc. doesn’t mean we will pay for it.” Huh? And it’s so much worse now. I was amazed at the issues insurance companies and self-insureds would fight in the old days. Oh, by all means, let’s take this dog to trial just because you hate the claimant! And quite a few of these cases involved taxpayer dollars. It is gallows humor indeed! Thanks for the link. I need all the humor I can get!
Since you used to represent them, you probably know all this. However, I will put this here for you or anyone, especially the Brits here, who won't shy from a bit of a dive into the labyrinthine hell that is American Medicare, and private insurance. It all sucks.
This is a few years old now, but it's a good primer on what is done with many meds I'm sure, not just Tecfidera. It's LONG, however, the first part is bitingly funny, so even if you don't read the whole thing, which is painstakingly documented and explained, you will get a good dose of gallows humor at least. Sadly, gallows humor is about the only type any of us can muster up about healthcare these days.
Wreck-fidera: How Medicare Part D has hidden the benefits of generic competition for a blockbuster Multiple Sclerosis treatment
I just started reading it, and they got me with “let’s get into the full informational colonoscopy” (paraphrasing..) Time for sleep. Will finish tomorrow. Thanks again!
Thank you Dr G for making us realize how the medicine industry actually works. I could never understand why Ocrevus without insurance is ~80k USD per dose in USA, but with this background it makes sense.
If Roche spend 5 billions getting Ocrevus ready and certrified they need to reclaim that cost somehow. UK as usual losing out because of its government managed health care.
As an aside it is quite stressful in US with the state of insurance in this country , as they can deny claims randomly and destroy you financially and medically, but if you are covered , the upside is all the medical innovations are happening in the US, and you can get first access to it .
I completely agree with Giovannoni's analysis. As an American and British citizen and having MS while living in both countries I've seen the differences in the systems as a patient and I've observed as a scientist how the lack of research funds has particularly hampered care here in the UK. As an American, I am annoyed that the rest of the (western and wealthy) world has subsidized treatments by our higher costs. As a Brit, I am annoyed that only 40% of people with MS are deemed worthy of treatment as persons with SPMS and PPMS are not commonly offered care here. In the US despite all its problems, 80-90% of MSers are given care and those numbers broadly hold through the rest of Western Europe too. The UK doesn't have perfect access like Americans think, they just triage care at a different point. However, I've been immensely grateful to have been offered alemtuzumab here in the UK and that I don't need to worry about high copays or other barriers to access given that I still have RRMS. I've also been utterly baffled by a lot of UK MSers seemingly justifying or being resigned to substandard care that exists here compared to other Western countries, often with the reasoning here that we have to shield our MS - no, you need to get the best treatment you can and expect treatment at the level of Germany/France/the Netherlands/US etc.
So can you tell me as an MSer who can not take the standard treatment for SpMS, due to side effects how I break through the NHS / Nice guidelines to get an alternative. I’m not resigned, I’m frustrated and have a sense of being on a scrap heap of disabled SPMSers. Otherwise I don’t consider my care substandard from my NHS caregivers.
I can't say of course as I am not a neurologist nor in your situation. I did however read the NICE guidelines before seeing my neurologist to advocate for myself.
I’m in the same boat ( no Siponimod for me) but I don’t think of myself as being in anyway ‘on a scrap heap’ . MS sucks but there are tens of thousands of people in the UK with worse conditions- cancer being the big one - and suffer or die because of a lack of suitable drugs/treatments
I try not to compare conditions. My sister died because of MS, not lack of treatment, side effects leading to sepsis. Each person is different. Each disease and drug comes with a risk. Scrap heap meaning no options of meds to prevent it, not that no one cares. Personally, despite advancing disability I live an active life with my off rd chair.
My point was that in the context of rising costs of treatments and drugs for all conditions and with people living for more years in old age all of us will probably have to face being on the ‘scrap heap’ - probably with cancer but could be for any of a whole range of conditions.
I my case I do compare conditions - with friends and relatives having died from cancer , strokes and in one case complications from Alzheimers. My view is very much that we are all in the same boat and equally deserving of treatment but sooner or later will have to appreciate the costs and limits, and at the end of the day I’m no more deserving than people with life limiting cancers etc etc
Yet somehow most Western nations would not have put either of you on the scrap heap. I think rather than comparing conditions in the NHS we should be comparing health systems - the NHS with other health systems like France, Germany, the Netherlands etc where you both would be offered more aggressive disease modifying treatment.
To me , it’s one of our misfortunes that the UK is totally wedded to the NHS. So much so that its ’change It at your peril’ although Reform UK make noises about private healthcare and insurance. The worry is that they don’t talk about hybrid systems (and certainly not about anything that smacks of arrangements in EU countries!)
I'm doing great. No disease progression after 2 rounds of alemtuzumab. I did a derisking protocol to reduce the incidence of secondary autoimmune disease by having a small 100mg rituxumab pulse after the B-cells rebounded each time. That also went great and *knock on wood* it's been since 2021. Before doing AHSCT I would do a 3rd or 4th round of alemtuzumab first if I have breakthrough activity. I would of course consider AHSCT if things were going badly. I'm of the mind to hit harder, younger. Though that was not my neurologist's attitude so I did have to fail 2 other drugs (copaxone and tecfidera) before alemtuzumab which took 10 years.
If you compared the cost of the Welfare bill for people with MS, against the bill for early diagnosis and quality treatment, I wonder how this balances the scales ? Investment in research and paying more for the drugs early on may well save on welfare.
As a person not on treatment, my EDSS has crept up. With that is a cost. To society and family and I’m one of far too many. Thinking of all the working years that are lost to MS just blows my mind.
Not simple though . In my case the ‘welfare bill’ is zero - my costs to the public purse are my DMT , annual MRIs and periodic blood tests. My early retirement was a personal choice - I could have carried on
You are right it’s never simple. There are many MSers who can’t carry on and get pushed out of work. Some have DMTs too. I wonder if we were given better, earlier treatments our ability to work would have reduced the welfare cost. Therefore allowing more money into meds and research.
I think the proposed question from Prof G has so many variables.
Gavin, I think there's some nuance here that you may just have missed (for once).
First, we should note that (despite their protestations) pharmaceutical companies overall are some of the most consistently profitable companies---and their main interest is now delivering profits to their shareholders. Keeping this short, there is ample evidence that they have repeatedly done this at the expense of patients; with incomes greater than the GDP of many countries, they can often do this with impunity. When I say expense, I'm talking tens or even hundreds of thousands of deaths and injuries. To quantify this financially, look at the fines imposed in the past by the FDA for off-label promotion, and the litigation related to (for example) rofecoxib.
A lot of the initial investment in time and money and researcher effort has historically been state-funded. (This is now collapsing in the USA, and innovation there will die). There has also been a large amount of frank meddling from drug companies, notably recently with the practically useless (and damaging) "anti-Alzheimers" monoclonals. https://drjo.substack.com/p/procrustean-water-torture
Next, we need to look in more detail at economics. The issue here is the madness that is the USA, which deforms world economics like a giant weight on a rubber sheet. Effectively, what is happening is *vast waste*, that in perspective makes comments like 'freeloading' diminutive and irrelevant! A tiny proportion of people in the US governs pretty much everything that happens, driving the extreme inefficiencies in the US healthcare system, where $12k is spent per person per year (over 17% of GDP) on outcomes that are manifestly inferior to those of pretty much every other developed country. If you "pay your fair share" then you are effectively subsidising this waste, and putting money in the pockets of people who are grossly disadvantaging their own citizens.
Jo, the UK Government has pushed against the analysis. The £45bn cost figure projected by the analysis is "not recognised by the department". The analysis also assumes that the billions needed for the trade deal will be diverted directly from existing frontline NHS services, which leads to the projected 229,000 excess deaths. The government countered this by stating that the deal will be funded by "allocations made at the spending review," so not necessarily from existing NHS budgets. While the analysis focuses heavily on the negative impacts of reduced service spending, ministers defended the agreement by arguing that it will allow NHS patients to access new, life-changing medicines they would previously have been denied. Let’s see how this pans out. Ministers also argue that the deal is a necessary measure to protect British-made drug exports, preventing them from facing tariffs of up to 100% threatened by the US; i.e., the UK Government's response to bullying.
The issues around bad apples are mainly regulatory, stemming from misaligned incentives and weak regulation and compliance within companies. This happens in almost all industries, e.g. the emissions fiasco with diesel cars. Bad apples do not mean the innovation system doesn’t work; it clearly works when you look at how we have transformed the management of most diseases over the last 50 years, including MS.
The problem the UK has had is that since NICE was created Pfizer, GSK, Novartis. Merck and, more recently, AstraZeneca (partially) have closed their UK-based research hubs. This has messed up a thriving research ecosystem and is an enormous cost to the UK.
My frustration is that I want a licensed EBV vaccine to prevent mono. Given the way the companies view the UK, we are unlikely to see action on phase 1 and 2 trials. Phase 3 may come to the UK because of our infrastructure for post-vaccine monitoring, but will we adopt the vaccine at a population level? That is another question.
Being selfish as an MS clinician, swapping out licensed anti-CD20 therapies for biosimilar rituximab is really preventing pwMS getting access to the superior treatments. This comes at a cost to individual patients and patient groups, which is why I use the rituximab vs obinutuzumab data in SLE and lupus nephritis. There really are differences between rituximab and ocrelizumab; why should my patients be forced to be treated with an inferior mAb? In 3-5 years' time, the argument will be moot as ocrelizumab biosimilars will be available at competitive prices.
Lots of talk about treatment drugs here but Professor G does refer to what is going to / likely to happen with the trials of EBV vaccines which , if successful could be an absolute god send and prevent millions of cases of MS . Freeloading backfiring on the UK?
Well you know my answer to all of the drug costs for pwMS. As soon as diagnosed, treat them with HSCT which is a one-off NHS cost in the region of £30,000. Don’t wait until smouldering MS sets in; treat at diagnosis. No one ever asks cancer patients to wait. One-off cost, £30k, done and dusted.
Professor John Snowden at Sheffield Hallamshire highlighted the frankly MASSIVE potential savings to the NHS when he presented a cost analysis to the EBMT in 2011. Imagine the savings that could have been made in the last 15 years…
The mortality rate is now so low it is hardly worth mentioning and the success rates if treated as soon as diagnosed are over 95% successful. I am regularly in touch with over 3,000 post HSCT for MS patients, many of whom are now +10 years or more since transplant and we are still relapse and progression free. I am at +11 years and my EDSS is still continuing to improve.
Very pleased for you and long may your improvement continue. I do find it difficult to understand all the reported success of HSCT so much of which seems to depend on age at treatment and I guess also on the number of lesions which develop before any significant symptoms and diagnosis. I’m not totally sure but some reports suggest that we can start accumulating lesions up to around 15 years before any noticeable symptoms and diagnosis .
Again , I’m not totally sure but some research reports that something like 40% of those treated go on to develop new lesions , relapses etc.
In my case my age at diagnosis ( early 50s) excluded me from HSCT .
On the more positive side and slightly to my surprise, 19 years of Avonex has resulted in just 1 new lesion . Walking can be difficult/ challenging but I am able to walk upstairs 2 steps at a time ( part of my exercise routine).
I would like to see the NHS ‘prescribing’ lifestyle changes ( diet, exercise and stress management) for all MS patients
It is nothing like 40% who go on to develop new lesions or disease progression! Even HIGHLY active RRMS are only 5% likely to progress. If you are in the UK search for the following Facebook Group where I can direct you to our files section which has details of all the published results. 40% “fail” is really so wrong and sounds suspiciously like something you may have been told by your neurologist. 😳
I see that there are a couple of trial to compare HSCT with 3 (4?) high efficacy DMTs . Results from one of them ( a UK one) to be reported some time 2027-28. So something or another in the use of HSCT should change in the following years.
Incidentally, in the back of my mind is something you said about one of my comments sounding ‘suspiciously like something a neurologist would say ‘ . the back of my mind has been wondering what on earth did that comment mean ? Not that it’s of any significance but are you doubtful of neurologists
The StarMS trial out of Sheffield Hallamshire will be reporting next year. The charity AIMS was involved in Round Table discussions with those running StarMS and have already posted that the results are expected to be a game changer. However, we as the UK, were already part of the MIST trial that fully reported already, showing that HSCT is significantly superior to any DMD. Sheffield already knew what StarMS would prove, but had to run their own trial to get NICE to listen! The NHS loves reinventing the wheel; StarMS cost £2.9 million.
Regarding Neurologists and with the exception of the few that have embraced HSCT, then yes I am doubtful of anything they say regarding HSCT for MS. I have lived and breathed HSCT for MS since 2014 and could write a book with all the incorrect info given to fellow MS patients about HSCT. I was UK accepted by haematology in 2014, but my neurologist refused to sign off on the procedure, despite the haematologist’s approval. So I went to Moscow and it cost me £35,000 and the rest as they say is now history. But that Neurologist will never be forgiven; if I hadn’t had the ability to research for myself, I am fairly certain by now I would be either permanently bed bound, or more likely dead.
For me it’s all academic ( too old for HSCT) I have seen many reports on success rates but to me, the big flaw in many of them is that there is no comparison with ‘success rates resulting from DMTs . For example, in my case my 10 year success rate on one of very first and now classed as low effectiveness was : no new lesions, no signs at all of any disability, and similarly no relapses . Even at 8 years I had zero, zero zero and that was in my mid 60s and on one of the DMTs with low efficacy. I don’t know for sure or rather I don’t know the details but the more recent high efficacy DMTs must have much better ‘success’ rates than Avonex. All academic to me
The whole system stinks.
“The global Multiple Sclerosis (MS) drugs market generates approximately $22.95 to $29.37 billion annually. This specialized space is heavily dominated by monoclonal antibodies, with Roche’s Ocrevus leading globally at about $7.6 billion in yearly sales.”
Top industry pay packages for recent fiscal years:
- Johnson & Johnson: Joaquin Duato leads the pack, with his compensation jumping to $32.8M.
- Novartis: Vasant (Vas) Narasimhan earns roughly $32M.
- Pfizer: Albert Bourla received $27.6M after overseeing recent strategic acquisitions.
- AstraZeneca: Pascal Soriot earned around $23.9M.
C.$30 billion a year revenues from MS therapies, yet not one tackles the real MS (smouldering MS), not one tackles the cause of MS (EBV), and not one reverses damage (remyelination therapy, therapies to promote axonal growth etc.).
Blaming "overpaid CEOs" and "evil pharma" is not helpful. At least we have Ocrevus thanks to them. What choices do we have if any ?
has China managed to do any better here ? They have been quite the hotbed of medical innovation off late, any updates ?
I hope you can bring this desperately needed argument for discussion at government level.
As a neurologist who has spent the last 25 years of my life developing new therapies for pwMS, including as GDTL for the ocrelizumab program at Roche, responsible for the design and initiation of the OPERA program, and over the last 12 years, as CMO of 3 biotechnology companies, I can say with confidence that your comments are well considered. Do CEOs of major pharmaceutical companies make too much money? Of course they do. Do their salaries substantially increase the cost of new drugs? No. Not really. I can say with certainty that the funding environment for novel therapies being developed by small, innovative companies has never been worse. This is driven by the chaos in the US government, global economic “interesting times” and loss of willingness to take risk. Drug development (especially in MS) is risky and costly. My current company has an exciting, novel drug with strong, replicated preclinical data demonstrating both remyelinating and synaptic protective properties. Despite having clean Ph1 data, whether we will ever be able to fund even an exploratory Ph2 POC study remains an open question. The bottom line is; if people of the globe want new, innovative therapies for devastating neurodegenerative diseases, at some point they will have to be willing to pay the price.
Quite agree and the same applies to drugs for all conditions. Everyone wants more and better treatments without fully appreciating the costs
I dont want your remyelinating drug. I want a cure.
Its all sickcare, job security, chasing VC for parallel drug development for more addictive chronic palliative care. Barn door, horse. $$
I agree that pharmaceutical innovation has to be funded and that companies deserve a fair return for genuine breakthroughs. However, I think the issue is more complex than describing countries like the UK as “freeloaders.”
The NHS has a duty to use finite public funds wisely. Every additional pound spent on one medicine is a pound that cannot be spent on cancer care, mental health, community services or other patients. NICE wasn’t created simply to drive down prices, but to ensure that limited NHS resources deliver the greatest overall health benefit.
I also think it’s important to recognise that the current imbalance isn’t solely the result of countries like the UK negotiating lower prices. It is also a consequence of the way the US healthcare system operates and the pricing strategies adopted by pharmaceutical companies, which have historically been able to command much higher prices there. That is a feature of the market, not something imposed by the NHS.
Finally, I don’t think the UK is simply a “freeloader”. British taxpayers already contribute significantly to medical innovation through publicly funded research, universities, the NIHR, clinical trials and the NHS itself. If the global model for funding pharmaceutical innovation is becoming unsustainable, perhaps the answer is a fairer international approach to sharing those costs, rather than expecting publicly funded health systems to pay more at the expense of other essential NHS services.
Something I haven't discussed is that Big Pharma are generally considered a blue-chip investment and is part of almost all private pension fund portfolios. Therefore, reducing their profits and dividends is like cutting your nose off to spite your face. Not to mention that the pharmaceutical industry punches above its weight in terms of its contribution to GDP. The exodus of big pharma from the UK has had a significant macroeconomic impact. The current government, with Patrick Vallance, is trying to row back against the tide. In my opinion, this is too little and probably too late; hence AstraZeneca's and Merck's (US) decisions to scale back or stop their UK investments, respectively.
Its interesting Gavin, I came across a video recently where this very knowledgeable person said Australia is a top destination for big pharma to do trials. I think is was due to favourable regulations, financial incentives and world class hospitals and medical professionals that encourages them to start their phase 1 trials in Australia.
Just a stream of consciousness post here.
What "global model" for funding pharmaceutical innovation? All I can see is a mish-mash of funding sources, some more reliable than others. It's not like there is some body that is designing fair funding strategies. Private equity is showing its rot at the core, and certainly philanthropy is not anything approaching a panacea, since individual philanthropists are notoriously fickle and can be their own weather systems that can end up wasting brainpower by driving their pet projects down unproductive roads (think Bill Gates and American education)
And at the end of the day, pharmaceutical companies are simply concerned with THEIR bottom line. If pressed hard enough (probably requiring thumb screws), their leadership would drop their already-gossamer fig leaves and admit that money is their ultimate driver and all the rest be damned. They are beholden to their shareholders first and always, and any public good is secondary. They will chase the money, and in a capitalist system, there is no amount of money that is ever, ever enough, meaning people/governments will always come to near-fisticuffs defining what a "fair return" means. And meanwhile our brains are melting.
And here I will simply comment on what the pharmaceutical companies' being able to command higher prices here in the US actually looks like from a vantage point on the ground.
Back in 2018? After being forced out of work by our monster, I had to be on my husband's insurance for a while before my own Medicare disability insurance kicked in (there is an 18 month waiting period - during which you've lost any employer-provided health insurance you may have had, which means if you don't have other sources of health coverage, you are potentially well and truly screwed). His insurance, in an extremely rare - in my experience - incidence of transparency for an insurance company, gave us an end-of-year accounting of all the monies they spent for our care. That year I was on dimethyl fumarate. My husband's insurance, for 12 months, paid $62,000 for that single medication. I can't recall what co-pay I paid per month, I THINK it was in the $60-100 range, but pay monthly I did.
I think as well as the complexities of economics that you have described, there is also the ongoing cost of using a cheaper drug off label if it is less effective. That would suggest that the patient is going to need more support, in the future, to live with their illness because they are more affected by it than if they had been treated with the licensed more effective medication. At some point the lifetime costs as a result of prescribing the cheaper alternative will become more than the lifetime costs of the licensed drug, assuming that the patient lives beyond that switchover point.
At some point, all innovator drugs come off patent and become cheaper. The relatively short patent life on medical innovation is the deal we, the population, make with pharma. We grant them exclusivity for a short period to recoup their investment and make a profit, and then the innovation becomes open for all to use. Allowing off-label prescribing when licensed options exist is reneging on this deal. Governments know this, but as the Americans are paying, who cares? The current US Government cares.
Yes, I understand that. I just think there is more to this than just economics, if we are talking about saving money by choosing what to prescribe.
Isnt that a bit of an assumption I.e that off label drugs are less effective?
The sad reality is that everything does come down to cost . The UK could provide the best drugs possible to treat every condition but ……… who pays?
Prof G was discussing using Rituximab rather than ocrelizumab, ofatumumab, and ublituximab. I.e. a cheaper, less effective drug. It wasn't my assumption, it was based on his evidence from Norway and Sweden.
The difference is small, if it exists. There's some debate about that.
Not that small when you look at the end organ. Brain volume loss on rituximab is probably worse than with interferon beta, compared to ocrelizumab being superior. Don't let relapses and MRI activity blind you.
Well said.
I'm going to go with Prof G on that one If he thinks there's a difference, that is good enough for me!
The difference is very small
Not that small if you measure it by brain volume loss or atrophy. It depends on how much you value the neuronal reserve or resilience required for healthy ageing.
It may be very small, but if considered more generally it is another example of hidden future cost to whom? The health system involved? Patients who later realise they didn't get the best treatment. I don't know about you, but I would be cross. I'm lucky, I am fine on Siponimod, the only treatment licensed for SPMS, unlike
unlike Helen!
In Australia where I live and I've got PPMS there was news in the last few days about Ocrevus, kesimpta and something else not being on the PBS anymore but the PBS folded and it kept those drugs on the PBS. It's A$17000 a bag for the infusion so I can understand the push to not have it on the PBS if another drug like rituximab does a similar result.
Good discussion. Welcome to the states, which are in chaos, as tout le monde knows. The last thing concerning the crazies here is spending money to maintain people with chronic illnesses. Regarding those evergreen patents, interferon beta now has a co-pay of +/- $800. And with Medicare privatized, (which it is, with horrible rules which most citizens do not understand), we are being forced to the cheapest drugs from the worst laboratories (you can look up the labs), even with the most expensive Medicare D policy, which solely covers drugs. The price of drugs has been driven down, however, there is no “donut hole“ relief after paying a ceiling amount. This is pure profit in the pockets of insurance companies from the extortionate policies.. don’t even get me started. I used to represent them.
Roger that, Goldweave. I often pictured two people in a room, each with a phone, just saying no, no and no. What insane country has a clause in medical policies stating “the approval of this blah blah drug/procedure etc. doesn’t mean we will pay for it.” Huh? And it’s so much worse now. I was amazed at the issues insurance companies and self-insureds would fight in the old days. Oh, by all means, let’s take this dog to trial just because you hate the claimant! And quite a few of these cases involved taxpayer dollars. It is gallows humor indeed! Thanks for the link. I need all the humor I can get!
Since you used to represent them, you probably know all this. However, I will put this here for you or anyone, especially the Brits here, who won't shy from a bit of a dive into the labyrinthine hell that is American Medicare, and private insurance. It all sucks.
This is a few years old now, but it's a good primer on what is done with many meds I'm sure, not just Tecfidera. It's LONG, however, the first part is bitingly funny, so even if you don't read the whole thing, which is painstakingly documented and explained, you will get a good dose of gallows humor at least. Sadly, gallows humor is about the only type any of us can muster up about healthcare these days.
Wreck-fidera: How Medicare Part D has hidden the benefits of generic competition for a blockbuster Multiple Sclerosis treatment
https://www.46brooklyn.com/research/2021/12/1/tecfidera
I just started reading it, and they got me with “let’s get into the full informational colonoscopy” (paraphrasing..) Time for sleep. Will finish tomorrow. Thanks again!
Thank you Dr G for making us realize how the medicine industry actually works. I could never understand why Ocrevus without insurance is ~80k USD per dose in USA, but with this background it makes sense.
If Roche spend 5 billions getting Ocrevus ready and certrified they need to reclaim that cost somehow. UK as usual losing out because of its government managed health care.
As an aside it is quite stressful in US with the state of insurance in this country , as they can deny claims randomly and destroy you financially and medically, but if you are covered , the upside is all the medical innovations are happening in the US, and you can get first access to it .
I completely agree with Giovannoni's analysis. As an American and British citizen and having MS while living in both countries I've seen the differences in the systems as a patient and I've observed as a scientist how the lack of research funds has particularly hampered care here in the UK. As an American, I am annoyed that the rest of the (western and wealthy) world has subsidized treatments by our higher costs. As a Brit, I am annoyed that only 40% of people with MS are deemed worthy of treatment as persons with SPMS and PPMS are not commonly offered care here. In the US despite all its problems, 80-90% of MSers are given care and those numbers broadly hold through the rest of Western Europe too. The UK doesn't have perfect access like Americans think, they just triage care at a different point. However, I've been immensely grateful to have been offered alemtuzumab here in the UK and that I don't need to worry about high copays or other barriers to access given that I still have RRMS. I've also been utterly baffled by a lot of UK MSers seemingly justifying or being resigned to substandard care that exists here compared to other Western countries, often with the reasoning here that we have to shield our MS - no, you need to get the best treatment you can and expect treatment at the level of Germany/France/the Netherlands/US etc.
So can you tell me as an MSer who can not take the standard treatment for SpMS, due to side effects how I break through the NHS / Nice guidelines to get an alternative. I’m not resigned, I’m frustrated and have a sense of being on a scrap heap of disabled SPMSers. Otherwise I don’t consider my care substandard from my NHS caregivers.
I can't say of course as I am not a neurologist nor in your situation. I did however read the NICE guidelines before seeing my neurologist to advocate for myself.
I’m in the same boat ( no Siponimod for me) but I don’t think of myself as being in anyway ‘on a scrap heap’ . MS sucks but there are tens of thousands of people in the UK with worse conditions- cancer being the big one - and suffer or die because of a lack of suitable drugs/treatments
I try not to compare conditions. My sister died because of MS, not lack of treatment, side effects leading to sepsis. Each person is different. Each disease and drug comes with a risk. Scrap heap meaning no options of meds to prevent it, not that no one cares. Personally, despite advancing disability I live an active life with my off rd chair.
My point was that in the context of rising costs of treatments and drugs for all conditions and with people living for more years in old age all of us will probably have to face being on the ‘scrap heap’ - probably with cancer but could be for any of a whole range of conditions.
I my case I do compare conditions - with friends and relatives having died from cancer , strokes and in one case complications from Alzheimers. My view is very much that we are all in the same boat and equally deserving of treatment but sooner or later will have to appreciate the costs and limits, and at the end of the day I’m no more deserving than people with life limiting cancers etc etc
Yet somehow most Western nations would not have put either of you on the scrap heap. I think rather than comparing conditions in the NHS we should be comparing health systems - the NHS with other health systems like France, Germany, the Netherlands etc where you both would be offered more aggressive disease modifying treatment.
To me , it’s one of our misfortunes that the UK is totally wedded to the NHS. So much so that its ’change It at your peril’ although Reform UK make noises about private healthcare and insurance. The worry is that they don’t talk about hybrid systems (and certainly not about anything that smacks of arrangements in EU countries!)
May i ask Prof Sarah how you are doing post Alemtuzumab? Have you ever considered AHSCT?
I'm doing great. No disease progression after 2 rounds of alemtuzumab. I did a derisking protocol to reduce the incidence of secondary autoimmune disease by having a small 100mg rituxumab pulse after the B-cells rebounded each time. That also went great and *knock on wood* it's been since 2021. Before doing AHSCT I would do a 3rd or 4th round of alemtuzumab first if I have breakthrough activity. I would of course consider AHSCT if things were going badly. I'm of the mind to hit harder, younger. Though that was not my neurologist's attitude so I did have to fail 2 other drugs (copaxone and tecfidera) before alemtuzumab which took 10 years.
If you compared the cost of the Welfare bill for people with MS, against the bill for early diagnosis and quality treatment, I wonder how this balances the scales ? Investment in research and paying more for the drugs early on may well save on welfare.
As a person not on treatment, my EDSS has crept up. With that is a cost. To society and family and I’m one of far too many. Thinking of all the working years that are lost to MS just blows my mind.
Not simple though . In my case the ‘welfare bill’ is zero - my costs to the public purse are my DMT , annual MRIs and periodic blood tests. My early retirement was a personal choice - I could have carried on
You are right it’s never simple. There are many MSers who can’t carry on and get pushed out of work. Some have DMTs too. I wonder if we were given better, earlier treatments our ability to work would have reduced the welfare cost. Therefore allowing more money into meds and research.
I think the proposed question from Prof G has so many variables.
Gavin, I think there's some nuance here that you may just have missed (for once).
First, we should note that (despite their protestations) pharmaceutical companies overall are some of the most consistently profitable companies---and their main interest is now delivering profits to their shareholders. Keeping this short, there is ample evidence that they have repeatedly done this at the expense of patients; with incomes greater than the GDP of many countries, they can often do this with impunity. When I say expense, I'm talking tens or even hundreds of thousands of deaths and injuries. To quantify this financially, look at the fines imposed in the past by the FDA for off-label promotion, and the litigation related to (for example) rofecoxib.
A lot of the initial investment in time and money and researcher effort has historically been state-funded. (This is now collapsing in the USA, and innovation there will die). There has also been a large amount of frank meddling from drug companies, notably recently with the practically useless (and damaging) "anti-Alzheimers" monoclonals. https://drjo.substack.com/p/procrustean-water-torture
Next, we need to look in more detail at economics. The issue here is the madness that is the USA, which deforms world economics like a giant weight on a rubber sheet. Effectively, what is happening is *vast waste*, that in perspective makes comments like 'freeloading' diminutive and irrelevant! A tiny proportion of people in the US governs pretty much everything that happens, driving the extreme inefficiencies in the US healthcare system, where $12k is spent per person per year (over 17% of GDP) on outcomes that are manifestly inferior to those of pretty much every other developed country. If you "pay your fair share" then you are effectively subsidising this waste, and putting money in the pockets of people who are grossly disadvantaging their own citizens.
I'll need to wrap up (although there's a lot more badness I might explore). The 'rebalancing' that has just happened is predicted to kill 229,000 people in the UK by 2036: https://www.theguardian.com/society/2026/jul/01/us-uk-drug-deal-could-result-in-229000-excess-deaths-in-england-analysis-suggests
My 2c, Dr Jo
Jo, the UK Government has pushed against the analysis. The £45bn cost figure projected by the analysis is "not recognised by the department". The analysis also assumes that the billions needed for the trade deal will be diverted directly from existing frontline NHS services, which leads to the projected 229,000 excess deaths. The government countered this by stating that the deal will be funded by "allocations made at the spending review," so not necessarily from existing NHS budgets. While the analysis focuses heavily on the negative impacts of reduced service spending, ministers defended the agreement by arguing that it will allow NHS patients to access new, life-changing medicines they would previously have been denied. Let’s see how this pans out. Ministers also argue that the deal is a necessary measure to protect British-made drug exports, preventing them from facing tariffs of up to 100% threatened by the US; i.e., the UK Government's response to bullying.
The issues around bad apples are mainly regulatory, stemming from misaligned incentives and weak regulation and compliance within companies. This happens in almost all industries, e.g. the emissions fiasco with diesel cars. Bad apples do not mean the innovation system doesn’t work; it clearly works when you look at how we have transformed the management of most diseases over the last 50 years, including MS.
The problem the UK has had is that since NICE was created Pfizer, GSK, Novartis. Merck and, more recently, AstraZeneca (partially) have closed their UK-based research hubs. This has messed up a thriving research ecosystem and is an enormous cost to the UK.
My frustration is that I want a licensed EBV vaccine to prevent mono. Given the way the companies view the UK, we are unlikely to see action on phase 1 and 2 trials. Phase 3 may come to the UK because of our infrastructure for post-vaccine monitoring, but will we adopt the vaccine at a population level? That is another question.
Being selfish as an MS clinician, swapping out licensed anti-CD20 therapies for biosimilar rituximab is really preventing pwMS getting access to the superior treatments. This comes at a cost to individual patients and patient groups, which is why I use the rituximab vs obinutuzumab data in SLE and lupus nephritis. There really are differences between rituximab and ocrelizumab; why should my patients be forced to be treated with an inferior mAb? In 3-5 years' time, the argument will be moot as ocrelizumab biosimilars will be available at competitive prices.
Very thoughtful piece.
https://www.science.org/doi/10.1126/scitranslmed.adz6566
Lots of talk about treatment drugs here but Professor G does refer to what is going to / likely to happen with the trials of EBV vaccines which , if successful could be an absolute god send and prevent millions of cases of MS . Freeloading backfiring on the UK?
Well you know my answer to all of the drug costs for pwMS. As soon as diagnosed, treat them with HSCT which is a one-off NHS cost in the region of £30,000. Don’t wait until smouldering MS sets in; treat at diagnosis. No one ever asks cancer patients to wait. One-off cost, £30k, done and dusted.
Professor John Snowden at Sheffield Hallamshire highlighted the frankly MASSIVE potential savings to the NHS when he presented a cost analysis to the EBMT in 2011. Imagine the savings that could have been made in the last 15 years…
But not safe for many. And it sometimes has only short terms benefits
The mortality rate is now so low it is hardly worth mentioning and the success rates if treated as soon as diagnosed are over 95% successful. I am regularly in touch with over 3,000 post HSCT for MS patients, many of whom are now +10 years or more since transplant and we are still relapse and progression free. I am at +11 years and my EDSS is still continuing to improve.
Very pleased for you and long may your improvement continue. I do find it difficult to understand all the reported success of HSCT so much of which seems to depend on age at treatment and I guess also on the number of lesions which develop before any significant symptoms and diagnosis. I’m not totally sure but some reports suggest that we can start accumulating lesions up to around 15 years before any noticeable symptoms and diagnosis .
Again , I’m not totally sure but some research reports that something like 40% of those treated go on to develop new lesions , relapses etc.
In my case my age at diagnosis ( early 50s) excluded me from HSCT .
On the more positive side and slightly to my surprise, 19 years of Avonex has resulted in just 1 new lesion . Walking can be difficult/ challenging but I am able to walk upstairs 2 steps at a time ( part of my exercise routine).
I would like to see the NHS ‘prescribing’ lifestyle changes ( diet, exercise and stress management) for all MS patients
HSCT UK
https://m.facebook.com/groups/ukhsct/
It is nothing like 40% who go on to develop new lesions or disease progression! Even HIGHLY active RRMS are only 5% likely to progress. If you are in the UK search for the following Facebook Group where I can direct you to our files section which has details of all the published results. 40% “fail” is really so wrong and sounds suspiciously like something you may have been told by your neurologist. 😳
I see that there are a couple of trial to compare HSCT with 3 (4?) high efficacy DMTs . Results from one of them ( a UK one) to be reported some time 2027-28. So something or another in the use of HSCT should change in the following years.
Incidentally, in the back of my mind is something you said about one of my comments sounding ‘suspiciously like something a neurologist would say ‘ . the back of my mind has been wondering what on earth did that comment mean ? Not that it’s of any significance but are you doubtful of neurologists
The StarMS trial out of Sheffield Hallamshire will be reporting next year. The charity AIMS was involved in Round Table discussions with those running StarMS and have already posted that the results are expected to be a game changer. However, we as the UK, were already part of the MIST trial that fully reported already, showing that HSCT is significantly superior to any DMD. Sheffield already knew what StarMS would prove, but had to run their own trial to get NICE to listen! The NHS loves reinventing the wheel; StarMS cost £2.9 million.
Regarding Neurologists and with the exception of the few that have embraced HSCT, then yes I am doubtful of anything they say regarding HSCT for MS. I have lived and breathed HSCT for MS since 2014 and could write a book with all the incorrect info given to fellow MS patients about HSCT. I was UK accepted by haematology in 2014, but my neurologist refused to sign off on the procedure, despite the haematologist’s approval. So I went to Moscow and it cost me £35,000 and the rest as they say is now history. But that Neurologist will never be forgiven; if I hadn’t had the ability to research for myself, I am fairly certain by now I would be either permanently bed bound, or more likely dead.
For me it’s all academic ( too old for HSCT) I have seen many reports on success rates but to me, the big flaw in many of them is that there is no comparison with ‘success rates resulting from DMTs . For example, in my case my 10 year success rate on one of very first and now classed as low effectiveness was : no new lesions, no signs at all of any disability, and similarly no relapses . Even at 8 years I had zero, zero zero and that was in my mid 60s and on one of the DMTs with low efficacy. I don’t know for sure or rather I don’t know the details but the more recent high efficacy DMTs must have much better ‘success’ rates than Avonex. All academic to me
It's a torturous business. Are there any wealthy countries who have struck the right sort of balance?