Ofatumumab is a self-administered treatment option, with final draft recommendation from the National Institute for Health and Care Excellence (NICE), for eligible adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease in England and Wales1,2
The final draft recommendation has been provided unusually quickly following Marketing Authorisation, granted on 6 April 2021 by the Medicines and Healthcare products Regulatory Agency (MHRA), recognising the value ofatumumab brings to patients and the NHS3. It is one of the first treatments to undergo the new MHRA authorisation process following the UK’s departure from the European Union
The decision is based on pivotal trial data that demonstrated the benefits of ofatumumab to patients with RRMS when compared to teriflunomide (a commonly prescribed oral disease modifying therapy for relapsing remitting MS) that delivered on the primary endpoint, less frequent relapses, and secondary endpoints, that demonstrated reduced inflammatory activity (evidenced by MRI scans), and prolonged time to disability worsening1
A treatment that offers self-administration at home, with initial guidance from a healthcare professional, gives people with RRMS more flexibility and reduces the burden on patients, healthcare professionals and the NHS which is facing capacity challenges in light of COVID-194
London, UK, 20 April 2021 — Novartis is proud to announce that eligible adult patients in England and Wales will soon have routine access to Kesimpta® (ofatumumab), the first self-administered, targeted B-cell therapy licensed for adults with relapsing forms of multiple sclerosis (RMS) with active disease, defined by clinical or imaging features. The news comes as the National Institute for Health and Care Excellence (NICE) published the Final Appraisal Document (FAD) recommending ofatumumab for the treatment of adults with relapsing remitting MS (RRMS) with active disease, defined by clinical or imaging features2.
NICE concluded that Kesimpta® is a cost-effective treatment that can be used first line or after other treatments for people with RRMS2. The FAD will form the basis of the final Technology Appraisal Guidance (TAG) that NICE will issue to the NHS in England and Wales. The Scottish Medicines Consortium (SMC) is expected to publish its final advice later this year.
RRMS is the most common form of MS, with around 85% of people considered to have RRMS at the point of diagnosis5. While MS symptoms are different for everyone, those living with RRMS often experience patterns of new or worsening of old symptoms, lasting for a period of 24 hours or more6.
A recent survey of the general public found that over half of those surveyed felt worried about going into hospital for their appointments in light of COVID-197. Despite the availability of a range of disease-modifying therapies (DMTs) for RRMS, there are significant needs that are not fully met by current options. Research suggests that many people with RRMS continue to experience disease activity or safety and tolerability concerns8,9.
Ofatumumab addresses an unmet clinical need for people living with RRMS as the first and only targeted B-cell therapy that can be self-administered at home via the Sensoready® autoinjector pen1. A treatment that offers self-administration at home, with initial guidance from an appropriately trained healthcare professional, gives people with RRMS more flexibility and reduces the burden on patients, HCPs, and the NHS as it faces capacity challenges in light of COVID-193,4. Furthermore, research published by Novartis in February this year found that MS patients and nurses preferred the Sensoready® autoinjector pen for self-administration over their current treatment devices10.
“People living with MS need access to a range of different treatment options so they can work with their doctor to find the one that’s best for them,” said David Martin, Chief Executive Officer, Multiple Sclerosis Trust. “As the first self-injectable B-cell therapy for RRMS, ofatumumab offers a new way for people living with multiple sclerosis to fit treatment into their lives. Without the need for regular hospital visits, even those who live a long way from a specialist centre will be able to access treatment that could reduce disease activity and help them continue to do the things that matter most to them.”
“The NICE recommendation of ofatumumab to treat relapsing remitting multiple sclerosis provides clinicians with a new, convenient treatment option,” said Consultant Neurologist, Dr. Owen Pearson at Morriston Hospital, Swansea. “Results from the ASCLEPIOS studies demonstrate that ofatumumab reduces disease activity and slows disability worsening. Today’s news brings the multiple sclerosis community, a much-needed self-administered treatment.”
This decision is based on the two Phase III ASCLEPIOS studies that met clinical and magnetic resonance imaging (MRI) endpoints, demonstrating a significant reduction in the number of relapses vs teriflunomide, evaluated as the annualised relapse rate1.
The primary endpoint from the studies was the annualised relapse rate (ARR), defined as the number of confirmed MS relapses per year, up to the end of the trial1. Secondary clinical endpoints were disability worsening confirmed at 3 months, disability worsening confirmed at 6 months, and disability improvement (i.e. lessening of disability) confirmed at 6 months; a prespecified meta-analysis of these endpoints used the combined data from both trials. Secondary MRI endpoints included the number of gadolinium-enhancing lesions per T1-weighted MRI scan, the number of new or enlarging lesions on T2-weighted MRI per year, and the annual rate of brain-volume loss1.
“We are proud to bring innovative medicines to people living with MS and the NHS. Ofatumumab is an effective treatment that can be administered at home, moving care outside of the hospital setting; and therefore supporting the NHS to recover from the pressures of COVID-19 and alleviating concern for people living with MS,” said Chinmay Bhatt, Managing Director UK, Ireland & Nordics for Novartis Pharmaceuticals. “This is something we are proud of, and we continue to build on our heritage in neuroscience and reimagine medicines.”
About Kesimpta® (ofatumumab) Ofatumumab is a fully human anti-CD20 monoclonal antibody (mAb) for adults with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features, which is intended to be self-administered by a once monthly injection, delivered subcutaneously1,11. As shown in preclinical studies, ofatumumab is thought to work by binding to a distinct epitope on the CD20 molecule, inducing potent B-cell lysis and depletion 3,12. Ofatumumab allows faster repletion of B-cells upon discontinuation versus other anti-CD20 mAbs, and therefore may offer flexibility in the management of RRMS13.
About ASCLEPIOS I and II studies The ASCLEPIOS I and II studies are twin, identical design, flexible duration (up to 30 months), double-blind, randomised, multicentre, Phase III trials evaluating the safety and efficacy of ofatumumab versus teriflunomide in adults with relapsing forms of multiple sclerosis (RMS)1. The studies were conducted in 37 countries and enrolled 1,882 patients between the ages of 18 and 55 years, with an Expanded Disability Status Scale (EDSS) score between 0 and 5.51. The primary endpoint from the ASCLEPIOS I and II studies was the annualised relapse rate (ARR), defined as the number of confirmed MS relapses per year, up to the end of the trial1.
Overall across both studies, 946 patients were assigned to receive ofatumumab and 936 teriflunomide, resulting in ofatumumab demonstrating a significant reduction in annualised relapse rate (ARR) by 50.5% (0.11 vs 0.22) and 58.5% (0.10 vs 0.25) compared with teriflunomide in ASCLEPIOS I and II, respectively (p<0.001 in both studies)1,14. Ofatumumab also showed a relative reduction in three- and six- month confirmed disability worsening (CDW) compared to teriflunomide: 34.4% (p=0.002) in three-month CDW (10.9% for ofatumumab and 15.0% for teriflunomide) and 32.5% (p=0.01) in six-month CDW (8.1% for ofatumumab and 12% for teriflunomide)1. In addition, results demonstrated a significant relative reduction in the mean number of both Gd+ T1 lesions (97.5% (0.01 vs 0.45) and 93.8% (0.03 vs 0.51), respectively, both p<0.001) and new or enlarging T2 lesions (82% (0.72 vs 4.00) and 84.5% (0.64 vs 4.15) versus teriflunomide, respectively, both p<0.001)1. The most important and frequently reported adverse events for ofatumumab are upper respiratory tract infections, systemic injection-related reactions, injection-site reactions, and urinary tract infections1.
About multiple sclerosis (MS) There are approximately 130,000 people with MS in the UK, and each year around 7,000 people are newly diagnosed with the condition15. MS is a chronic disorder of the central nervous system (CNS) that disrupts the normal functioning of the brain, optic nerves and spinal cord through inflammation and tissue loss16. The evolution of MS results in an increasing loss of both physical and cognitive functions (e.g. mobility problems, numbness, bladder and bowel problems, and problems with thinking, learning, and planning)17. There are three types of MS: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)18. Patients with relapsing forms of MS (RMS) – including RRMS and SPMS with active disease – experience distinct attacks of symptoms, known as relapses5,19. Around 85% of people are considered to have RRMS at their point of diagnosis20. SPMS, which typically follows from an initial RRMS course, is characterised by a gradual worsening of neurological function over time and can be described as active (with relapses and/or evidence of new magnetic resonance imaging [MRI] activity) or not active (no evidence of current activity)19,21.
About Novartis in multiple sclerosis (MS) Novartis has a strong ongoing commitment to neuroscience and to bringing innovative treatments to patients suffering from neurological conditions where there is a high unmet need. The Novartis MS portfolio includes Gilenya®▼ (fingolimod, an S1P modulator), which is licensed in the UK and Europe for the treatment of adults and children aged 10 years and older with highly active relapsing-remitting MS (RRMS). Mayzent®▼ (siponimod) is licensed in the UK and Europe for the treatment of adult patients with secondary progressive MS (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity. Extavia® (interferon beta-1b for subcutaneous injection) is licensed in the UK and Europe to treat people with RRMS (≥2 relapses in the last 24 months), people with SPMS with active disease (evidenced by relapses) and people who have had a single clinical event suggestive of MS with an active inflammatory process.
About Novartis Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 130,000 people of nearly 150 nationalities work at Novartis around the world.
In the UK, we employ approximately 1,500 people to serve healthcare needs across the whole of the UK, as well as supporting the global operations of Novartis. Since 2014, Novartis has invested over £200 million in R&D and is a leading sponsor of clinical trials, in the UK. For more information, please visit www.novartis.co.uk.
IPSOS. Living with MS: Multiple Sclerosis Syndicated Patient Community. March 2019
Ross A, Besser C, Naval S, et al. Patient and Nurse Preference for Sensoready® Autoinjector Pen Versus Other Autoinjectors in Multiple Sclerosis: Results from a Multicenter Survey. ePoster presentation at: ACTRIMS Forum 2021; February 25-27, 2021.
Bar-Or A, Fox E, Goodyear A, et al. Onset of B-cell depletion with subcutaneous administration of ofatumumab in relapsing multiple sclerosis: results from the APLIOS bioequivalence study. Poster presentated at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS); 27-29 February 2020; West Palm Beach, FL.
Smith P, Kakarieka A, Wallstroem E. Ofatumumab is a fully human anti-CD20 antibody achieving potent B-cell depletion through binding a distinct epitope. Poster presented at ECTRIMS; 14–17 September 2016; London, UK.
Savelieva M, Kahn J, Bagger M, et al. Comparison of the B-Cell Recovery Time Following Discontinuation of Anti-CD20 Therapies. ePoster presented at ECTRIMS; October 25–28, 2017; Paris, France.