Dimethyl fumarate

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid and is named after the earth smoke plant (Fumaria officinalis). DMF combined with three other fumaric acid esters (FAEs) is solely licensed in Germany as an oral therapy for psoriasis (trade name Fumaderm®). Since 2013, it has been used to treat adults with relapsing multiple sclerosis (trade name Tecfidera®). In 2017, a new oral formulation of DMF (trade name Skilarence®) was approved by the European Medicines Agency (EMA) for use in Europe as a treatment for moderate-to-severe plaque psoriasis. DMF is thought to have immunomodulatory properties without causing significant immunosuppression. Dimethyl fumarate (DMF) is the methyl ester of fumaric acid and is named after the earth smoke plant (Fumaria officinalis). DMF combined with three other fumaric acid esters (FAEs) is solely licensed in Germany as an oral therapy for psoriasis (trade name Fumaderm®). Since 2013, it has been used to treat adults with relapsing multiple sclerosis (trade name Tecfidera®). In 2017, a new oral formulation of DMF (trade name Skilarence®) was approved by the European Medicines Agency (EMA) for use in Europe as a treatment for moderate-to-severe plaque psoriasis. DMF is thought to have immunomodulatory properties without causing significant immunosuppression. DMF has also been applied as a biocide in furniture or shoes to prevent growths of mould during storage or transport in a humid climates. However, due to cases of allergic reactions after skin contact, DMF-containing consumer products are no longer authorised to be manufactured (since 1998) or imported (since 2009) in the European Union. Nevertheless, these measures have had no bearing on DMF’s use in medical settings, in which the medical authorities have granted its usage for psoriasis and multiple sclerosis due to the clinical evidence supported by different clinical trials and real world evidence (or daily clinical practice). Dimethyl fumarate is used to treat psoriasis in an oral formulation mixed with related compounds as well as in pure oral formulations. It is also used in oral formulations to treat adults with relapsing multiple sclerosis. For the treatment of psoriasis, DMF is dosed in 30 mg and 120 mg tablets, and the maximum daily dose is 720 mg. Meanwhile, for multiple sclerosis, the doses are 120 mg and 240 mg of DMF, with a maximum daily dose of 480 mg. Fumaric acid´s first medical use was described in 1959 by Walter Schweckendiek, a German chemist, and was a topical formulation for psoriasis. The Swiss company Fumapharm eventually brought Fumaderm®, an oral formulation of DMF (along with some monoesters) to market for psoriasis in Germany in 1994, where it has become the most frequently used first-line systemic psoriasis treatment. Based on the efficacy and safety of this formulation, and evidence that DMF was the main active component, an oral formulation of DMF was developed by Almirall. This oral formulation, under the brand name Skilarence®, was approved in Europe by the EMA in June 2017 for the treatment of moderate-to-severe plaque psoriasis in adults. Some people using the topical formulation as a cream for psoriasis also had MS and their MS improved; this led to clinical studies for that purpose. Fumapharm was one of the laboratories involved and Biogen Idec collaborated with them on the research and then acquired Fumapharm in 2006. Another company, Aditech Pharma in Sweden, had also been researching oral formulations of DMF for MS and in 2010, the Danish company Forward Pharma acquired Aditech's patents. Meanwhile, Biogen continued developing its oral formulation of DMF from Fumapharm under the code name BG-12; it was approved, under the trade name Tecfidera, for the treatment of adults with relapsing forms of MS in March 2013. Biogen priced the drug at $54,000 per year in the US. It was approved in Europe in 2014. In the UK NICE issued a guidance recommending the drug as cost-effective, but only for patients who do not have highly active or rapidly evolving severe relapsing–remitting multiple sclerosis and only if Biogen agreed to provide it at a discount. Forward and Biogen entered into patent litigation in many jurisdictions; in 2017 the companies settled the litigation, with Biogen paying Forward $1.25 billion, with the potential for up to 10% of royalties depending on what happened with the patents in various jurisdictions.