Rituximab combination therapy

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A dark age is when society regresses; it goes backwards in time. The shocking revelations in last week’s New England of Journal of Medicine on the dire situation of some type 1 diabetics upset me and indicates we may be entering a dark age. An age when we are forcing our patients to turn their backs on innovation because they, or society, can’t afford to purchase the necessary medications to allow them to treat their disease. 

“The price of insulin has risen to a level where some patients have reported rationing their medication, which has resulted in worsening glycemic control and, in some cases, diabetic ketoacidosis and death. Approximately 90% of insulin sold in the U.S. is manufactured by one of three companies (Eli Lilly, Novo Nordisk, and Sanofi). The rising cost of insulin in the United States can be attributed primarily to two phenomena. First, U.S. law allows pharmaceutical manufacturers to price their products at whatever level they believe the market will bear and to raise prices over time without limit. Second, direct competition in the insulin market is lacking.” 

Excerpt from Michael Fralick & Kesselheim. The U.S. Insulin Crisis — Rationing a Lifesaving Medication Discovered in the 1920s. N Engl J Med 2019; 381:1793-1795.

I can only conclude that the politicians, with their neoliberal agenda, are failing these patients and society in general. The plight of type 1 diabetics is just the tip of the iceberg in a healthcare system that is being ripped apart by raw and unbridled capitalism. This is why the Labour party in Britain are warning us about the potential consequences for the NHS when we lose the protection of the EU post-Brexit.  

Is the rationing of DMTs happening to people with MS? Several pwMS have commented on this blog how unaffordable DMTs are in the U.S. if you don’t have medical insurance and/or are covered by one of the socialist healthcare systems you are being forced to forego treatment. For me, as an academic working in MS, this is worrying because as we move into an era of combination therapies we are going to have to make combinations of treatments affordable. If one company controls all the components of the combination they can then price the therapy at an affordable price. However, if the components of the combination are controlled via different companies then the price of the individual components may make combination therapies too expensive.  

We have been making the case of building a sandwich with a potent anti-inflammatory at the base and superimposing on top centrally acting anti-inflammatories, neuroprotective and remyelination therapies, neurorestorative treatments and anti-ageing agents. In addition to this, we may need a cocktail of drugs targeting comorbidities, either treating them or preventing them. As you can see the cost of treating MS will rapidly become prohibitively expensive. 

In HIV Gilead tackled this problem by in-licensing different drugs from other companies to create their polypills. I envisage this happening in MS. If it doesn’t happen then the price of treating MS will beyond most people. 

At the moment anti-CD20 therapies are rapidly becoming the base of the treatment pyramid, but the innovator anti-CD20 compounds are simply too expensive at present for competitors to use them as part of a combination therapy strategy. Even when ofatumumab and ublituximab get licensed for treating MS the cost of anti-CD20 therapies, in general, is unlikely to fall significantly. Maybe as part of our #AffordableDMT initiative, we can get wide adoption of rituximab biosimilars and use these more affordable anti-CD20 biosimilars at the base of the pyramid? 

The problem we have is that rituximab is not licensed to treat MS. Outside of Sweden and the Kaiser Permanente in the U.S.  systematic rituximab prescribing is patchy. Most HCPs are not confident enough to take on the risks of prescribing rituximab off-label. Even in Sweden the medical insurance company that covers Swedish neurologists in relation to their practice has said they won’t be able to cover their rituximab prescribing because of the extent of its use in Sweden. I am told that the Swedish government is having to create a bespoke medical insurance policy to cover system-wide off-label prescribing. Surely a better solution would be for the Swedish government to license rituximab as a treatment for relapsing MS and then this issue will go away? 

If rituximab is licensed as a treatment for MS in Sweden then under reciprocal recognition rules in Europe we may be able to start using rituximab in the UK and other EU countries. This is assuming it happens before Brexit-related divorce laws disconnect us from Sweden and the EU. Another option would be for the NHS to license rituximab in the UK. I am not sure of the NHS has the will and/or the mechanisms for licensing a therapy for a specific disease, but it is something worth exploring. This would be a real game-changer both in the UK and internationally. This will allow us academics to at least build a combination therapy strategy with an affordable anti-CD20 at the base of the pyramid. This will allow us to test our induction-maintenance therapy hypothesis using generic drugs; for example, induction with rituximab followed by leflunomide as maintenance therapy. 

Getting rituximab licensed to treat MS could be another strategic objective of our GRAD Initiative (Grass-Roots Affordable DMT Initiative). What do you think? This may appeal to low- and middle-income countries, particularly a country such as India that has a large and burgeoning biosimilars industry. 

Please don’t be shy we need #AffordableDMT champions and wider engagement from the MS community. If you would like to get involved please get involved and register your interest. I would also like ideas from the wider community about how we get rituximab licensed as a treatment for MS. If you can’t beat Pharma you might as well join them 😉

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

5 comments

  • “We have been making the case of building a sandwich with a potent anti-inflammatory at the base and superimposing on top centrally acting anti-inflammatories, neuroprotective and remyelination therapies, neurorestorative treatments and anti-ageing agents.”

    Unfortunately, having MS has made me very cynical. The scenario painted above is science fiction. I don’t see any trials looking into such combinations of therapies. Where are we with “centrally acting anti-inflammatories….neurorestorative treatments….”? Can you put a timeframe on when a pollypill encompassing these various therapies will be available? Given that some neuros are still prescribing Copaxone, I think the combination therapy approach will come too late for current MSers (I reckon I’ve got c.15 years left).

  • https://youtu.be/Ow8lCYPPzNY
    This -very interesting- 14 min. report shows what US Diabetes 1 patients do to have access to lifesaving insulin. A patient from the clip moved from US to UK just for this reason…

    As for Rituxan, it is included in the recent ICER list for unessecary price rise

    https://www.fiercepharma.com/pharma/icer-lambasts-abbvie-s-humira-genentech-s-rituxan-and-more-for-unsupported-price-hikes

    Pharma prices are spiraling out of control it seems…

  • I believe I’ve read a 25mg intrathecal injection of rituxan leads to complete peripheral cd20 cell depletion. I wonder if this is as effective as 1000mg intravenous for managing MS. If so, rituxan can be incredibly affordable.

    Considering disease location, med costs, and ease of testing csf to monitor disease activity, I really wonder if Omaya reservoirs or something similar aren’t the keystone of MS management in the future.

    If MSers are losing brain because effective meds are too expensive…it might make the risks associated w Omaya reservoir combined w benefit of effective treatment worth it. Right now, the vast majority of MSers are just losing brain on ineffective or no meds.

  • So glad profG is glass half full, but having sent about 3 years looking into licencing cladribine, the government is NHS cannot be the licence holder and the purchaser without a change in regulation. So hold a licence costs a company thousands and thousands of pounds, and they have responsibilities. The regulators are virtually paid for by pharma and turkeys don’t vote for Christmas, even if I wish they did. The needs to be a political will and how many politicians are in the back pocket of pharma. Let the US near the NHS and is is dead if it is not there already as it is being privatised by the back door.

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