- Diroximel fumarate is a next generation, at-home, oral fumarate treatment, with established efficacy and well-characterised safety, for people living with relapsing-remitting multiple sclerosis (RRMS)1,2
- Phase 3 data and real-world evidence (n=263, based in the US) have demonstrated that treatment with diroximel fumarate results in low discontinuation rates due to its gastrointestinal (GI) tolerability profile3,7
- The recommendation strengthens Biogen’s established MS portfolio and ongoing commitment to introducing therapies that positively impact the lives of those living with MS
Biogen UK announced on April 13 2022 that the National Institute for Health and Care Excellence (NICE) has published a positive Final Appraisal Document (FAD) recommending VUMERITY® (diroximel fumarate), an oral fumarate, for the treatment of adults living with active RRMS[*] in England, Wales and Northern Ireland. The medicine was fast tracked to FAD enabling all eligible patients to have access to diroximel fumarate as soon as possible, providing another important option when considering the right treatment for their individual needs.1
Approximately 115,880 people are currently living with MS in England, Wales and Northern Ireland.8 It is estimated that 85% are living with RRMS, the most common form of the condition.9 Diroximel fumarate offers those living with RRMS a treatment option with an improved gastrointestinal (GI) tolerability profile and comparable efficacy and safety characteristics to established treatment dimethyl fumarate (due to bioequivalence).3-6 The new oral fumarate treatment can reduce the severity and frequency of burdensome GI events like nausea, vomiting, diarrhoea and upper and lower abdominal pain, whilst also offering the convenience and flexibility to be taken with or without food.2-6,10
“For some people, their current oral fumarate may cause them to experience stomach issues which can affect their daily activities and productivity. Diroximel fumarate successfully decreases the chances of relapses but also causes fewer gastrointestinal side effects, which is critical in supporting people to start and stay on treatment. Today’s fast-tracked approval of diroximel fumarate follows approval in Scotland, providing equitable access across the UK. These positive recommendations enable us to offer an alternative at-home, oral DMT while avoiding a potential switch to an injectable therapy.Dr Martin Duddy, Consultant Neurologist, Royal Victoria Infirmary, Newcastle
“Effective treatments that fit into daily life can help people live a life with MS that is not defined by MS. People living with MS can be confident in the established efficacy of this new oral treatment that has fewer stomach problems to manage. This can mean that they don’t have to factor their medication in relation to mealtimes.” said David Martin, CEO, MS Trust.
NICE’s decision was based on data from pivotal phase 3 trials (EVOLVE-MS-1 and EVOLVE-MS-2), which compared diroximel fumarate and dimethyl fumarate and demonstrated similar efficacy safety profiles.4,5 GI events, such as nausea, vomiting, diarrhoea and upper and lower abdominal pain were less severe and lasted fewer days with diroximel fumarate compared with dimethyl fumarate and therefore were less likely to interfere with patients’ daily lives.5,6 In addition, since diroximel fumarate’s launch in the US, real-world evidence has reinforced the GI tolerability profile and confirmed that patient experience demonstrated in clinical trials is consistent with clinical practice. The real-world retrospective analysis of persistence[†] and adherence in DRF-treated patients (n=263) showed high overall persistence over 12 months (~81.8%) [95% CI, 76.1–86.3], low discontinuation rate due to GI AEs (4.6%, 12/263) and high adherence to therapy (mean PDC 89.7%),[‡] aligning with expectations based on DRF clinical trials.7
“Following the Scottish Medical Consortium approval, the recommendation of diroximel fumarate by NICE marks our third MS product launched in the last 12 months. This is a significant milestone in our ambition to advance treatment and improve outcomes for people living with RRMS,” said Dr Mihaela Vlaicu, Head of Medical Affairs, Biogen UK and Ireland. “For nearly 25 years, we have led in the research and development of new MS therapies, continually striving to help address the diverse needs that people living with MS may have throughout their lives.”
NICE’s recommendation follows the Scottish Medicine Consortium’s acceptance earlier this year, and the Medicines and Healthcare products Regulatory Agency (MHRA) and European Union authorisation in December 2021. The NICE FAD represents finalisation of the NICE Committee recommendations and forms the basis of the final Technology Appraisal Guidance (TAG) which is expected to be published in May. Once a positive recommendation is made through the fast-track appraisal process, NHS England commissioners have committed to providing funding for the technologies within 30 days of guidance publication.
1. National Institute for Health and Care Excellence. Final appraisal document. Diroximel fumarate for treating relapsing remitting multiple sclerosis. April 2022.
2. Electronic Medicines Consortium. Vumerity 231 mg gastro-resistant hard capsules. Available at: https://www.medicines.org.uk/emc/product/13087/. Accessed: March 2022.
3. Palte MJ, et al. Adv Ther 2019;36(11):3154-3165.
4. Wehr YA, et al. Presented at 2018 American Academy of Neurology Annual Meeting; 21–27 April, 2018; Los Angeles, USA. P403.
5. Naismith RT, et al. Mult Scler 2020 26(13):1729-1739.
6. Naismith RT, et al. CNS Drugs 2020;34(2):185-196.
7. Larger et al. Multiple Sclerosis Patients Treated With Diroximel Fumarate Over 1 Year in the Real-world Setting Have High Rates of Persistence and Adherence. 37th Congress of the European Committee for Treatment & Research in Multiple Sclerosis. 2021, P838.
8. MS Trust. Available at: https://mstrust.org.uk/a-z/how-common-multiple-sclerosis. Accessed March 2022.
9. NICE. Multiple Sclerosis: How common is it? Available at: https://cks.nice.org.uk/topics/multiple-sclerosis/background-information/prevalence/#:~:text=190%20per%20100%2C000%20in%20England%20(around%20105%2C450%20people.
10. MS Society. Relapsing Remitting MS. Available here: https://www.mssociety.org.uk/about-ms/types-of-ms/relapsing-remitting-ms. Accessed March 2022.
11. Diroximel fumarate. Patient Information Leaflet. DRF Patient Leaflet GB (medicines.org.uk). Accessed March 2022.
12. Tecfidera Data on file #028. Post Marketing Exposure Experience. March 2021.
13. Electronic Medicines Consortium. Tecfidera 120mg and 240mg gastro-resistant hard capsules. Available at: https://www.medicines.org.uk/emc/medicine/28593. Accessed March 2022.
14. Wray et al. Diroximel Fumarate in Patients With Relapsing-Remitting Multiple Sclerosis: Interim Safety and Efficacy Results From the Phase 3 EVOLVE-MS-1 Study, 37th Congress of the European Committee for Treatment & Research in Multiple Sclerosis. October 13-15, 2021, P739.
About diroximel fumarate
Diroximel fumarate is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis. It is an oral fumarate with an improved chemical structure to dimethyl fumarate. Once in the body, diroximel fumarate rapidly converts to monomethyl fumarate, the same active metabolite of dimethyl fumarate providing similar efficacy and safety profiles.2
Diroximel fumarate is another treatment option for RRMS and has a safety and efficacy profile consistent with dimethyl fumarate, with lower rates of GI AEs.3-6
Common adverse events are (may affect up to 1 in 10 people); inflammation of the lining of the intestines (gastroenteritis), being sick (vomiting), indigestion (dyspepsia), inflammation of the lining of the stomach (gastritis), digestive system problems (gastrointestinal disorder), burning sensation, hot flush, feeling hot, itchy skin (pruritus), rash, pink or red blotches on the skin (erythema). Side effects which may show up in blood or urine tests; proteins (albumin) in urine (proteinuria), increase in levels of liver enzymes (ALT, AST) in the blood. Very common (may affect more than 1 in 10 people); reddening of the face or body feeling warm, hot, burning, or itchy (flushing), loose stools (diarrhoea), feeling sick (nausea), stomach pain or stomach cramps. Side effects which may show in blood or urine tests; ketones in urine; low levels of white blood cells (lymphopenia, leukopenia) in the blood.1,11
Diroximel fumarate was first approved by the U.S. Food and Drug Administration in October 2019. Since its launch in the U.S., real-world data have reinforced the GI tolerability profile and confirmed that the experience demonstrated in clinical trials is consistent with clinical practice.7 Diroximel fumarate is approved for use in adult with RRMS in US, Europe, and Israel.
About dimethyl fumarate
Dimethyl fumarate, a treatment for RRMS in adults, has been shown to reduce the rate of MS relapses, slow the progression of disability and impact the number of MS brain lesions, while demonstrating a well-characterised safety profile in people with relapsing forms of MS. More than 537,432 patients have been treated with dimethyl fumarate (as of 1st of Sept 2021), representing 1,119,293 patient-years of exposure (as of 30th Jun 2021), across global clinical trial & post-marketing settings.12
Common (≥1/100 to <1/10) adverse reactions includes gastroenteritis, lymphopenia, leucopenia, burning sensation, hot flush, vomiting, dyspepsia, gastritis, gastrointestinal disorder, aspartate aminotransferase and alanine aminotransferase increased, pruritus, rash, erythema, proteinuria, feeling hot, albumin urine present and white blood cell count decrease. Very common (≥1/10) adverse reaction includes flushing, diarrhoea, nausea, abdominal pain upper, Abdominal pain, ketones measured in urine.13
For more information on dimethyl fumarate and diroximel fumarate please refer to the SmPC: Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk)
About EVOLVE-MS-1 and EVOLVE-MS-25,6,14
EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing diroximel fumarate safety, tolerability, and efficacy in RRMS patients. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory. The interim finding, as of September 2020; 1057patients were enrolled; median exposure was 2.0 (range, 0.0–2.1) years. Adverse events (AEs) occurred in 88% (932/1057) of patients, the majority were mild (29%; 307/1057) or moderate (50% 527/1057) in severity. Overall treatment discontinuation was 8%; and <1% due to GI AEs. At week 96, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (63.6% p<0.0001) and adjusted annualised relapse rate (ARR)[§] was low 81% reduction (95% CI, 78.1–84.1) p < 0.0001) compared to 12 months before study entry.
EVOLVE-MS-2 was a phase 3, randomised, double-blind, head-to-head, 5-week study evaluating the gastrointestinal tolerability of diroximel fumarate 462 mg vs dimethyl fumarate 240 mg, administered twice daily in patients with relapsing–remitting multiple sclerosis, using two self-administered gastrointestinal symptom scales: Individual Gastrointestinal Symptom and Impact Scale (IGISIS) and Global Gastrointestinal Symptom and Impact Scale (GGISIS). The primary endpoint was the number of days with an IGISIS intensity score ≥2 relative to exposure. Other endpoints included the degree of gastrointestinal symptom severity measured by IGISIS/GGISIS and assessment of safety/tolerability. Results diroximel fumarate -treated patients experienced a statistically significant reduction (46%) in the number of days with an IGISIS symptom intensity score ≥2 compared with dimethyl fumarate -treated patients (rate ratio [95% confidence interval]: 0.54 [0.39–0.75]; p=0.0003). Lower rates of gastrointestinal adverse events (including diarrhoea, nausea, vomiting, and upper and lower abdominal pain) were observed with diroximel fumarate than dimethyl fumarate (34.8% vs 49.0%). Fewer patients discontinued diroximel fumarate than dimethyl fumarate because of adverse events (1.6% vs 5.6%) and gastrointestinal adverse events (0.8% vs 4.8%).
Biogen-163820 | Date of preparation: April 2022