Small Molecules

An Overview of Emerging Therapeutic Options in the Treatment of Psoriasis

Melinda Gooderham, MD, MSc, FRCPC

Disclosures

Skin Therapy Letter. 2013;18(7) 

In This Article

Fumaric Acid Esters

Fumaric acid esters (FAEs) are a group of small molecules that have been used for many years in Germany to treat psoriasis. Initial use for psoriasis can be traced to 1959 by the German biochemist Schweckendiek who himself suffered from psoriasis. More recently, FAEs have gained attention as an immunomodulatory therapy for multiple sclerosis.[27] Since 1994, FAEs have been available as a mix of dimethyl fumarate (DMF) and three salts of ethylhydrogenfumarate under the trade name Fumaderm® (Fumapharm/Biogen Idec) and widely used in some European countries.[27,28] The mechanism of action is not completely understood, but one theory suggests that FAEs increase glutathione level in the cell, resulting in inhibition of nuclear factor-kappa B (NFκB) translocation into the nucleus and, thereby, a reduction of inflammatory cytokine production.[27] Other immunologic effects are discussed in more detail elsewhere.[28] The use of Fumaderm® has been limited by its gastrointestinal side effects in up to 30% of patients, thus, a newer formulation of DMF is being investigated.

Dimethyl Fumarate (FP187)

FP187 is a patented controlled-release erosion matrix tablet of DMF produced by Forward-Pharma GmbH. A pivotal Phase 2 study has been completed (ClinicalTrials.gov, identifier NCT01230138) which examined the safety and efficacy of different doses of FP187, but the results have not yet been reported. A Phase 3 study is registered to compare 500 mg of FP187 (250 mg BID) to the commercially available Fumaderm® at a dose of 720 mg (240 mg three times daily) over 20 weeks (ClinicalTrials.gov, NCT01815723) and is likely to start in the fourth quarter of 2013.

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