Tag: GRAD initiative

Rituximab combination therapy

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

Affordable DMTs

My post on the ‘Damp Squib’ has upset several close colleagues. I need to explain my reasons for doing it; the main one being is that I am very frustrated that change happens so slowly, whereas shit happens so quickly.

The catalyst for our Barts-MS off-label initiative was my sabbatical 5 years ago and kicked-off with a blog post I did on the 3rd October 2014. I am ashamed that it is now 5 years since our first activities in this space and nothing has really changed for people with MS living in resource-poor environments. I can count the number of centres on one hand (excluding rituximab users, which is really a high-cost DMT) that are using off-label DMTs and they are all in high-income countries. As a proponent of ‘Time is Brain’ in MS, and that includes the brains of pwMS living in resource-poor countries, I have to ask myself how many brains have been shredded whilst we procrastinate. We want this campaign to become urgent. 

A good analogy would be the anti-retroviral access campaign that was run to get people with HIV living in low- and middle-income countries onto treatment. Why can’t we do something similar for people with MS?

When I criticise my colleagues I want to make it clear that there is likely to be an unconscious bias against off-label prescribing of generics and biosimilars despite a robust evidence base. This is the invisible elephant in the room. Whenever I have attempted to shift this issue to the top of the agenda it gets watered down and put at the bottom of the list of solutions for treating people with MS in low- and middle-income countries. In addition, the term off-label tends to be avoided and replaced by euphemisms, for example, repurposed. 

I suggest we avoid off-label and use a neutral term that will be all-encompassing and acceptable to all parties. I, therefore, suggest referring to these treatments as “affordable DMTs”, which is counterbalanced by the term “high-cost DMTs”. Affordable captures everything we are trying to do without stating the obvious. The term ‘affordable DMT’ solves the issue as it not only refers to off-label DMTs, but includes generic, biosimilar, and bioequivalent DMTs, and unlicensed and compounded DMTs and any other variation that emerges. In addition, what is affordable may vary from one country to the next.

It is clear that a lot of people in the MS community don’t want to rock the boat when what we really need to do is capsize the boat. Many of my colleagues, including me, are so conflicted that we tend to toe the Pharma-line because we have been indoctrinated by the system, i.e. the only solution to treat and manage MS is with high-cost innovative DMTs. This is clearly not the case and we need to collect and summarise the evidence to make the MS community realise that there are other ways to manage this disease. 

So I want to rebrand this the GRAD Initiative (Grass-Roots Affordable DMT Initiative), which may be more acceptable to the wider community and potentially neutralise our cognitive biases. The plan that I am currently formulating is based on a simple grass-roots movement, starting small and local:

  1. Identifying local MS champions and creating an international network of these champions.
  2. Creating and disseminating an essential affordable DMT list with detailed protocols on how to use each agent.
  3. Modified diagnostic criteria for use in resource-poor environments; these will need to country-specific.
  4. Protocols for derisking and monitoring DMTs in these environments.
  5. Creating a platform to allow neurologists and other HCPs from these countries to share their experience.
  6. Putting in place the suitable infrastructure to collect real-world data to assess the effectiveness of using affordable DMTs in these environments.

We are hoping to try to do something small and local in Africa, India and Pakistan. We plan to visit all these countries/regions in 2020.

Please don’t be shy we need champions and wider engagement from the MS community to make this happen. Please get involved and register your interest.

CoI: multiple

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