How Does an Ingredient in Sour Candy Become a Blockbuster?



Gerald Clarke
11/01/2013

In 1959 W. Schweckendiek used fumaric esters to treat his psoriasis. In 2009, after people were injured by ‘poisoned chairs’, importing products containing dimethyl fumarate was banned in the EU. Now, in Q3 2013 it brought in $286 million for Biogen Idec as a treatment for Multiple Sclerosis. This unlikely success story manages to evoke many of the key themes being discussed in the pharma industry, from drug discovery and screening to pricing and the cost of drug development. It also raises issues that may become more interesting over the coming years such as homemade pharma.

Banned

Available relatively cheaply from chemical companies in bulk, it serves many purposes. One of the uses of fumaric acid, a precursor of dimethyl fumarate, is as a food additive (it even has its own E number: E297) used to make food taste sour, it is used in sour candy. Dimethyl fumarate was also used as a biocide on furniture to stymie fungal growth on sofas in shipping, but it caused hundreds of cases of skin reactions in consumers. Several retailers faced class-action lawsuits and were forced to withdraw the sofas from the market as, in low concentrations, dimethyl fumarate acts as an allergic sensitiser. Following this, the EU Commission banned the sale of consumer products containing more than 0.1ppm dimethyl fumarate.

Cost

One of the many talking points about this widely available chemical’s use as a medicine is its price tag. One year of Biogen Idec’s Tecfidera costs $55,000. With the equivalent of a year’s supply available for only a few hundred dollars if bought directly from chemical companies, critics are questioning Tecfidera’s seemingly inflated price. This, of course, is a somewhat unfair argument, since first Fumapharm AG and their eventual buyer; Biogen Idec invested large amounts of money in undertaking clinical trials to prove the safety and efficacy of Tecfidera as a treatment for multiple sclerosis. Dimethyl fumarate has long been produced (often in Europe) as a treatment for psoriasis, none of the companies who produce it for this purpose took the step of investing in trials into further applications. It is also the case that Biogen Idec states in Tecfidera’s Orange Book entry that it is a delayed release formulation, while the raw chemical on it’s own has a relatively short half-life. Biogen Idec certainly deserve to recoup their investment and have their initiative rewarded, but in an environment that is hostile to the perceived avarice of the pharmaceutical industry, this is certainly going to be a lightening rod for drug-pricing criticism.

Garage Chemists

Something raised in the comments of Derek Lowe’s blog on the topic caught my eye, with the chemical easily and cheaply available from chemical manufacturers, commenter David Borhani wondered whether patients might begin to seek a grey-market source of their drugs. Intellectual property is becoming difficult to control in all industries with even industries thought to be immune, such as manufacturing finding themselves at risk from new technologies such as 3D printing. Could pharma be next in line to find their products chipped away by the home grown peer-to-peer pirates? Of course, a more likely threat to Tecfidera could be hot button topic of off-label prescription. With several companies producing dimethyl fumarate for psoriasis at a much cheaper pricepoint, it will be interesting to see how Biogen Idec makes the case for their product.

Questions Raised

One of the many questions raised in this case is; how could this be a known pharmaceutical with immune modulating effects for almost 55 years before alternative uses were sought? How could half a century go by without anyone considering this as holding more potential? One possibility is that it is an irritant and can cause gi problems, but these problems seem to be reduced in Tecfidera. Could it be the case that there are many more metaphorical babies being thrown out with the bath water?

An interesting aside is that the mechanism of action for the drug’s effects is still not known definitively. Over that past decade or so, pharmaceutical companies had moved increasingly towards a target-based model of drug design and development with recent research pushing the number of known genetic variants associated with MS risk to 110. The results of this more knowledge-based approach weren’t as rich as anticipated given the large investment made into this research. With this in mind, some companies are moving back to a phenotypic based approach and the story of Tecfidera, potentially pharma’s newest blockbuster, will certainly register in the minds of those about to make a decision about what path to choose.