“It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness, it was the spring of hope, it was the winter of despair, we had everything before us, we had nothing before us, we were all going direct to Heaven, we were all going direct the other way – in short, the period was so far like the present period, that some of its noisiest authorities insisted on its being received, for good or for evil, in the superlative degree of comparison only.”
A Tale of Two Cities (1859) is a historical novel by Charles Dickens.
Although global inequality seems to be receding since its peak in 2016 we still live in a world of ‘the haves’ and ‘the have nots’. A stark reminder of this is for people living with MS and having to experience global inequality in access to effective MS therapies.
My memory of a relatively wealthy young woman with MS in Banglore, India, who I met back in 2014 when on sabbatical, reminds me that we have so much still to do. This woman was having to raise money from her extended family, and her social network, to purchase her weekly Avonex injection one syringe at a time. If she couldn’t raise the necessary money she would simply miss that week’s injection. Her neurologist informed me that since developing MS her family was facing financial ruin. The question I asked myself later was ‘Why wasn’t her neurologist treating her with an alternative DMT that she could afford?”. Therein lies the problem, i.e. how do we get the neurology community and wider MS community to accept that there are cheaper, effective, alternatives for managing MS in resource-poor environments.
Please note that I prefer using the term resource-poor environments and try to avoid using the term resource-poor country. This is deliberate because even in rich countries there are pockets of disenfranchised people without access to healthcare, for example, refugees, immigrants and the medically uninsured. Britain may soon be included. In the event of a no-deal Brexit, a large number of foreign EU nationals with MS living in this country may have their free-access to the NHS withdrawn. At present, there is no clarity on how the EU and the UK will deal with healthcare coverage in the event of a no-deal Brexit.
As an MSologist with a large number of EU nationals under my care, the prospect of a no-deal Brexit gives me sleepless nights. How will we respond to a scenario of a home office and/or NHS official demanding that we stop prescribing high-cost DMTs to some of our patients? Rebound MS disease activity on withdrawing natalizumab or fingolimod is potentially life-threatening.
It is essential that the MS community seek solutions for treating people with MS in resource-poor environments. This is why we are exploring different solutions including prescribing low-cost off-label DMTs, developing compassionate access schemes, creating low-cost generics and buyers clubs. Another grass-roots solution is to use compounding pharmacies.
In short, compounding refers to the process of creating a pharmaceutical preparation or drug by a licensed pharmacist to meet the needs of a community when a commercially available drug does not meet those needs or is too expensive. When you look at our list of essential off-label DMTs we could add dimethyl fumarate to that list. There will criticism from Pharma that compounded, or home-brew, DMF formulations are inferior. But when it comes down to a choice of either bankrupting your family due to the high-costs of innovative treatments or taking a chance on a compounded formulation of the drug I know which one I would choose.
We have previously covered the topic of a DIY DMF formulation on this blog and you can read how to make your own DMF tablets via this website. I am not advocating that individual pwMS do their own compounding, but this could be done centrally via a licensed compounding pharmacy. The quality of the compounded formulations could then be tested using an international quality control laboratory. The latter could be funded by the global MS community (MSIF) or charities with a vested interest in finding solutions to this problem, for example, the Melinda and Bill Gates Foundation or the Wellcome Trust.
Obviously, Pharma will object and produce papers such as the one below claiming their product is superior and that compounded formulations are inferior, but maybe this will nudge them to do something about the hundreds of thousands of untreated people living with MS in resource-poor environments. To be fair to Biogen they were the only Pharma company who responded to my call-to-arms a few years ago about trying to find a solution to treating MS in resource-poor environments and I note that one of their senior executives has already signed up to our Grass Roots Off-Label DMT Initiative (GROLDI). To do this is bold and I suspect brave, but their action shows you that even Pharma executives are prepared to acknowledge that access to DMTs is a global problem.
Please note our Barts-MS Essential Off-label DMT list has just been expanded to include compounded DMF and the generic version of DMF that is used to treat psoriasis.
- Generic dimethyl fumarate (Skilarence)
- Compounded dimethyl fumarate
*on the 19th WHO Model List of Essential Medicines (April 2015)
Compounding pharmacies could be one way of improving access to DMTs in low-income countries. Do you think compounding pharmacies will address the problem of access to DMTs in resource-poor environments? Let us know your thoughts.
If you are interested in helping address the issue of lack of access to MS DMTs in resource-poor countries and environments post please sign-up to our Grass Roots Off-Label DMT Initiative (GROLDI).
Boulas P (Biogen, Cambridge, MA, USA). Compounded Formulations of Dimethyl Fumarate Show Significant Variability in Product Characteristics. Drug Res (Stuttg). 2016 May;66(5):275-8.
BACKGROUND: Pharmacy compounded products are not regulated to the same standards as commercially available, approved products, increasing potential safety and efficacy risks to patients. This report describes an in vitro study examining consistency of content and release profile of compounded dimethyl fumarates.
METHODS: Samples of compounded dimethyl fumarate (cDMF-A, cDMF-B, cFumaderm) from separate Austrian compounding pharmacies were analyzed for drug content, uniformity of dosage, impurity, and in vitro release.
RESULTS: The average dimethyl fumarate (DMF) content ranged from 102.5 to 96.7% of the 120 mg content listed on the product labels. While the DMF capsule-to-capsule content of cDMF-A was somewhat uniform (~20% difference), there was greater variability amongst cDMF-B and cFumaderm capsules (> 30% difference). Impurity testing revealed 2 and 4 unknown components within cDMF-A and cDMF-B, respectively, with levels ranging from 0.05 to 0.81% of total drug content. In in vitro testing of cDMF-A,>10% (12 mg) of DMF was released after 120 min in simulated gastric fluid and 17% (20 mg) released in simulated intestinal fluid after 60 min. While minimal amount of DMF was released from cDMF-B in simulated gastric fluid, 50% (60 mg) of DMF was released after 60 min in simulated intestinal fluid. Similarly for cFumaderm, a fraction (< 20 mg) of the 120 mg target dose was released after several hours in simulated intestinal fluid. The uniformity of release rates across capsules varied significantly.
CONCLUSION: These results demonstrate that compounded fumarates are not equivalent to licensed products and may present unknown safety, efficacy, or quality risks.