Professor Gavin Giovannoni (Prof G) and his team of clinicians and researchers at Barts and at the Royal London Hospital — like many of their medical colleagues — are in frequent contact with pwMS (people with multiple sclerosis), many of whom are untreated. The reason that these pwMS are on no treatment is often economic. No treatment due to economic reasons and can occur in both developed as well as in developing countries around the globe. In order to address this problem of poor access to treatment, the team has compiled a list of drugs with scientific evidence supporting their efficacy as MS treatments, which are available at an accessible price — the Barts-MS Essential Off-label DMT List. The drugs on the list have expired patents, which is why they can be purchased at a relatively low price. In addition, these drugs are unlicensed in MS. The reason is they were developed to treat diseases other than MS and their treatment effect upon MS was discovered by clinicians years later.
Prof G and his team made their list available online and continued at the same time to look for other solutions to the issue of patient access. Recently, they have shared some new thoughts on this blog. Below, I will discuss some as this important matter is close to my heart.
My name is Sagit Weiss and I am a physician specialist in internal medicine and a biologist. I worked for many years in the pharmaceutical industry. Recently I have been working on alternative funding models for medical research, where the profit mechanisms do not require or rely on patents. Examples of such research include topics such as the repurposing of generic drugs or physical exercise in diseases management. The chance that such projects will generate patents is very low and hence they will be hard to fund using today’s funding models.
It is noteworthy that such research on generic drugs can still deliver a lot when carried forward such as was the case in MS (dimethyl fumarate, rituximab or alemtuzumab and others). Most of the drugs on the Barts’ list are repurposed generic drugs.
Soon after I started this project, I was diagnosed with Parkinson Disease. In 2018, a neurologist from Jerusalem, Professor David Arkadir shared with me that in his clinic, a fifth of people with Parkinson are treating themselves with mannitol. It was shown in vitro (by Professor Daniel Segal from the University of Tel Aviv, 2013) to interfere with the aggregation of alpha-synuclein (which is believed to be a critical part of the underlying pathology in Parkinson disease) and to cure Parkinson in two animal models. It is a generic drug, also sold online as a food supplement at £20 per kg.
One of the recent posts by Prof G proposed a political campaign targeted at representatives of the World Health Organisation (WHO) and health ministries, to move MS up the WHO agenda and change the way drugs’ regulators work to stimulate generic drugs’ repurposing into un-licensed indications.
The WHO, is a specialised agency of the United Nations, interacts with agencies that specialise in intellectual property and trade agencies among a few others. In 2015, the UN Secretary-General announced the creation of a high-level panel on innovation and access to health technologies (1). The outlined mandate was to “… recommend solutions for remedying the policy incoherence between the justifiable rights of inventors, international human rights law, trade rules and public health …”.
It took me a lot of time to realise that contrary to the UN opinion, the prevailing consensus is there is no incoherence: healthcare innovation is incentivised by pricing, which is protected by intellectual property (and trade) laws. The price of innovative drugs is directly linked to the high costs of drugs’ research and development (R&D). Delinking them for example by favouring the use of off-patent drugs in un-licensed indications would jeopardise healthcare innovation.
According to the UN, there are now numerous new mechanisms to incentive health technology innovation (1). This alone exemplifies the struggle of the WHO in dealing with access in the full context of the various UN stakeholders and related legislations. Taking this into consideration, solving the mentioned incoherences might need to happen before the WHO is in a position to favour generic drugs repurposing.
Coming back to the prevailing belief, I feel that things could be clarified by quantifying on one hand on ‘the need for innovative therapies’, their ’R&D cost’, ‘incentive’ for funders, end-product ‘price’ and on the other hand the ‘lack of access’ and the ‘lack of innovation’. These numbers could be fed into an algorithm that would create a chart representing the trade-off between the need for incentives and the need to care for those who fall between the cracks of innovation.
The trade-off will line would determine distinct but agreed systems, hosting two different R&D funnels, one for patented drugs and one for the others, such as those on the Barts-MS Essential Off-label DMT list. In that new system, where profits won’t require or rely on patents, new profit-making mechanisms will be needed to incentivise investors.
We have just seen how the UN is struggling to align its stakeholders. Although Prof G proposed a political campaign, I would like to suggest we start exactly as he did in his blog, with wide information and engagement campaigns, to feed a grass-root-movement. First, because that movement claiming its due access to healthcare would be the best way to establish the right balance versus potential innovative therapies for the future.
Second, because changes have to be claimed loud and clear by patients and the public to overcome prejudice among prescribers. Education is needed to overcome resistance among patients. We can’t expect any change in practice to take root as long as we believe that no treatment is better than taking an off-patent un-licensed drug.
Transparent information will need to go out there, carried by the campaign both to doctors and the public. An honest description of all aspects of progress in medicine should be given, on what the pharmaceutical industry did for us (we couldn’t be having this discussion without antipsychotics, antiepileptics and many others drugs), the role of academia and clinicians in innovation, and what we need, including when we live in a resource-poor environment. Demystify the differences between on and off-patent drugs, licensed and un-licensed indications.
To empower the emergence of a grass-roots movement via access to information (including this post), sources of information must be stripped of all technical jargon and made easy to understand to everyone, whatever their background. There must be universal access to knowledge spreading vertically and horizontally through outreach programmes to people with influence inside different communities. Too many times I have been told that it is risky to let the public decide. Information and education experiments have shown that with appropriate methods it is possible to inform and activate the general public.
Such a campaign is possible and I dare to say has good chances of success. Indeed, access to medical treatments has been discussed for years in tabloid newspapers and via crowdfunding campaigns. Medical treatment crowdfunding campaigns have reached a very large number of people, via channels such as GoFundMe.com; $5bn has been raised since 2010 (2). An article in Forbes 2018 entitled ‘People Are Raising $650 Million On GoFundMe Each Year To Attack Rising Healthcare Costs’ addresses the issue at the heart of this campaign(3). Another website, Youcaring helped raise roughly $ 400 millions (2). This is not about the money, but the massive potential for public engagement. Even if the vast majority of the fundraisers are from the US, and in spite of the cases of fraud – less than 0.1% according to gofundme.com (4), there is an opportunity to join forces with patients, their families and the public via these portals. Even if this is not a ‘traditional initiative’, this journey might lead us to make a fundamental change in society, as profound as the change the environment movement after 50+ years of work. The environmental activists faced much more resistance than the pharmaceutical industry; environmentalists didn’t have the sympathy people can get with medical problems. In addition, the environmentalists didn’t have the support of a professional community, such as the medical profession, but they managed to reach a universal level of awareness and got buy-in from the general population at a level we can only dream of getting with our #AffordableDMT initiative. The environmental movement has very high public awareness and it has been successful because of public engagement, the creation of new laws, taxation policy and the formation of new industries.
The environmental movement also teaches us that campaigns need to global without borders. The issue at stake is huge and is a universal enterprise, far beyond MS and can’t really be dealt with one disease at a time. We won’t elevate the issue above the noise when next door is a parallel campaign for another disease claiming the same issues. This is the time to pool our resources to maximise public attention.
To get a breakthrough we need to reach out to HCPs from other sectors of medicine, colleagues involved in research that is attempting to repurpose generic drugs, to public health or health policy officials and other stakeholders to counter resistance and scepticism – and join forces to fight a common cause. More importantly, we need to remember that we are just members of the public ourselves. By sharing information with them we would hope to move access to affordable medical treatment up the agenda.
What we also need the regulators to create a new dedicated entity for clinicians &/or academics to submit evidence for approval of off-patent drugs in new indications, with a time & cost-effective pathway and the necessary guidance.
A few thoughts before closing:
- We need to learn from other areas and be street-smart.
- An exemplar is the successful multi-stakeholder campaign that led to global access to antiretrovirals for the treatment of HIV-AIDS.
- A huge amount of community attention and support is converging on gofundme.com. This phenomenon is not passive and has funded treatment for a huge number of patients. Why don’t we work together?
- Partner with generic drugs companies, patient associations (including buyers’ clubs) and medical charities.
- Is it not time to create a health citizenship education program for patients and their families?
- Shall we crowdsource the solution(s) by organising a Hackaton, based on the Unlimited Inclusivity Hackaton?
Sagit Weiss, London November 2019
Essential Grassroots Affordable DMT (GRAD) Initiative List
- Generic dimethyl fumarate (Skilarence)
- Compounded dimethyl fumarate
*on the 19th WHO Model List of Essential Medicines (April 2015)
- Massacesi L et al. Azathioprine versus beta interferons for relapsing-remitting multiple sclerosis: a multicentre randomized non-inferiority trial. PLoS One. 2014 Nov 17; 9(11): e113371. doi:10.1371/journal.pone.0113371.
In the article it mentions “Prof G and his team made their list available online ” can someone point me to where this list can be seen?
Generic dimethyl fumarate (Skilarence)
Compounded dimethyl fumarate
*on the 19th WHO Model List of Essential Medicines (April 2015)
Thanks for the list.
So would I be in my rights to ask my Neuro (East Lancs NHS) if there is a possibility of prescribing me any of these? (I’m supposed to be SPMS and deteriorating) with me paying if necessary?
The pathway to Parkinson’s takes a surprising twist
Thank you, this is interesting and if confirmed, might explain why some Parkinson patients taking mannitol have experienced symptomatic improvement.
Thanks for your eloquent post Sagit.
Some great comments, my favourite:
changes have to be claimed loud and clear by patients and the public to overcome prejudice among prescribers
Sums up grass roots action. Prescribers can be so old-school and stuck in the mud!