Oral Fumarate (Dimethyl Fumarate and Diroximel Fumarate) Efficacy and Safety Data Presented

Data presented at the European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress in Stockholm, Sweden September 11-13, 2019 show that dimethyl fumarate (Tecfidera; Biogen, Cambridge, MA) consistently provides safe and effective treatment of relapsing-remitting multiple sclerosis (RRMS). 

“Biogen’s new data underscore Tecfidera’s role as a meaningful long-term therapy option for relapsing MS, with many patients in the study experiencing no relapses or progression in their disability over a 10-year period,” said Alfred Sandrock, Jr., MD, PhD, executive vice president and chief medical officer at Biogen. “We are proud of the strong legacy Tecfidera has achieved over the years and are excited to continue building our franchise of fumarate products with the potential addition of diroximel fumarate. As a next-generation fumarate, diroximel fumarate offers a differentiated gastrointestinal tolerability profile and, if approved, will be a strong choice for physicians and patients with relapsing MS to consider.”

Results from the phase 3 ENDORSE extension study (NCT00835770) show that participants (n= 192) with at least 10 years of follow show that approximately half (51%) had no relapses and 64% had no confirmed disability progression over the 10-year period. Additionally, 79% maintained the ability to walk without significant disability. There was no increased occurrence of serious
infections. In a separate meta-analysis of real-world data from 18 databases, dimethyl fumarate was found to be significantly more effective than interferon beta, glatiramer aetate, and teriflunomide in reducing annualized relapse rates (ARRs) and decreasing time to first relapse. Efficacy of dimethyl fumarate was similar to fingolimod, but less than natalizumab or alemtuzumab. 

A new oral fumarate, diroximel fumarate (Biogen and Alkermes [Waltham, MA], is under investigation for the treatment of RRMS. In previous trials, diroximel fumarate has been shown to have greater gastrointestinal tolerability compared with dimethyl fumarate. Data from the phase 3 EVOLVE-MS-1 (NCT02634307) study of diroximel fumarate presented at the meeting showed that less than 1% of participants discontinued treatment because of gastrointestinal adverse events. Interim exploratory analysis of data from the trial suggest that diroximel fumarate reduced ARR by 79.4%, the mean number of gadolinium-enhancing lesions by 64.3% from baseline, and that these results were similar in newly diagnosed participants treated with diroximel fumarate. 

Diroximel fumarate is currently under review with the Food and Drug Administration (FDA) with a target action date in the fourth quarter of 2019. If approved by the FDA, Biogen intends to market diroximel fumarate under the conditionally approved
brand name Vumerity.