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MHRA authorisation for Vumerity® for RRMS

Posted in Industry News on 20th Nov 2021

The Medicines and Healthcare Regulatory Agency (MHRA) has granted marketing authorisation for diroximel fumarate as oral treatment for relapsing-remitting multiple sclerosis

  • VUMERITY® (diroximel fumarate) is a next-generation oral fumarate treatment for adults with relapsing-remitting multiple sclerosis (RRMS) with established efficacy and well-characterised safety, building on Biogen’s leadership in MS oral therapies
  • Phase 3 data have demonstrated that treatment with diroximel fumarate results in low discontinuation rates due to its gastrointestinal (GI) tolerability profile1-4
  • MHRA authorisation, followed by the European Union authorisation, provides people living with RRMS in the UK and Ireland with another important option when considering the right treatment for their individual needs

Biogen UK announced on November 18th 2021 that the Medicines and Healthcare Regulatory Agency (MHRA) has granted marketing authorisation for diroximel fumarate to treat adults with relapsing-remitting multiple sclerosis (RRMS). Diroximel fumarate is a next-generation oral fumarate with an improved tolerability profile and comparable efficacy and safety characteristics of dimethyl fumarate (TECFIDERA®).1-4 In the UK, approximately 130,000 people are living with MS and nearly 7,000 people are newly diagnosed each year.5

“Everyone’s experience of MS is unique, it can be unpredictable and emotionally and physically challenging,” said Dr Mihaela Vlaicu, Head of Medical Affairs, Biogen UK and Ireland. “It is important that people have MS treatment options available to them that can be easily integrated into their daily life. This new option provides flexibility for people living with MS, to be treated without having to think about dietary restrictions or when to take a dose in relation to mealtimes.”

The MHRA and European Commission (EC) approval of diroximel fumarate is based on data from pharmacokinetic bridging studies comparing diroximel fumarate and dimethyl fumarate to establish bioequivalent exposure of monomethyl fumarate, the active metabolite, and relied on the long-term efficacy and safety profile of dimethyl fumarate. The approval was also based on findings from EVOLVE-MS-1 and EVOLVE-MS-2.3,4 GI events such as, nausea, vomiting, diarrhoea and upper & 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, which may lead to improved long-term adherence and continuity on therapy.4,5

“The approval of diroximel fumarate by the MHRA, and subsequently by the EC, highlights the importance of treatment adherence, which can make a meaningful difference on treatment outcomes when living with a chronic disease,” said Jonathan Randell, Senior Director, Value & Access, Biogen UK and Ireland.

It provides a new oral treatment option for patients with low gastrointestinal discontinuation rates, that may help patients to start and adhere to treatment. This is another milestone in our ambition as a company to advance treatment and improve outcomes for people living with MS and we are working towards ensuring access across the UK&I.

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.6 Biogen continues to file regulatory submissions in other countries.

References:

1.     Wehr YA, et al. Presented at 2018 American Academy of Neurology Annual Meeting; 21–27 April, 2018; Los Angeles, USA. P403.

2.     Palte MJ, et al. Adv Ther 2019;36(11):3154-3165.

3.     Naismith RT, et al. Mult Scler, 2020 26(13):1729-1739.

4.     Naismith RT, et al. CNS Drugs 2020;34(2):185-196.

5.     MS Society. MS In The UK. MS in the UK | Multiple Sclerosis Society UK (mssociety.org.uk) Accessed November 2021.

6.     Liseno J, et al. Multiple Sclerosis Patients Treated with Diroximel Fumarate in the Real-World Setting have High Rates of Persistence and Adherence. Neurology. April 13, 2021; 96 (15 Supplement).

7.     Diroximel fumarate. Patient Information Leaflet. DRF Patient Leaflet GB (medicines.org.uk)

8.     Tecfidera Data on file #028. Post Marketing Exposure Experience. March 2021

9.     Dimethyl fumarate.  Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk)

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.

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.1-4

Common (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.7

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.8

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.9

For more information on dimethyl fumarate please refer to the SmPC:  Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk)

About EVOLVE-MS-1 and EVOLVE-MS-2 3,4

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 March 2018; 696 patients were enrolled; median exposure was 59.9 (range: 0.1–98.9) weeks. Adverse events (AEs) occurred in 84.6% (589/696) of patients; the majority were mild (31.2%; 217/696) or moderate (46.8%; 326/696) in severity. Overall treatment discontinuation was 14.9%; 6.3% due to AEs and <1% due to GI AEs. At week 48, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (77% p<0.0001) and adjusted annualised relapse rate was low (0.16; 95% confidence interval: 0.13–0.20).

EVOLVE-MS-2 was a phase III, 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 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%).

About Biogen

Pioneering in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases in addition to related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a portfolio of medicines and potential therapies in neuromuscular, neurodegenerative, acute neurology, and ophthalmology disease areas. Biogen believes that biosimilars, and their associated cost-savings, are fundamental to safeguarding future healthcare, and is focusing on advancing one of the most diversified pipelines in neuroscience, transforming the standards of care for patients in several areas of high unmet need.

In 2020, Biogen launched a 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil fuels across the company’s operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.

To learn more, please visit www.biogen.uk.com, www.biogen.ie