• Novartis announces that the peer-reviewed journal Neurology and Therapy1 has published new data on COVID-19 infections in people living with relapsing remitting multiple sclerosis (RRMS) treated with Kesimpta® (ofatumumab)
• A very small proportion (1.5%) of those fully vaccinated and treated with ofatumumab developed COVID-19. Despite being fully or partially vaccinated all patients with breakthrough COVID-19 recovered
• At the time of data cut-off (September 25, 2021), no cases of COVID-19 were reported after the booster vaccination
• Novartis is committed to generating evidence to better understand the severity and outcomes of COVID-19 in people receiving ofatumumab to help support informed decision making in relapsing remitting (RRMS) treatment selection
Novartis announced on March 23 2022 that the peer-reviewed journal Neurology and Therapy1 has published new data on COVID-19 infections in people living with relapsing remitting multiple sclerosis (RRMS) treated with Kesimpta® (ofatumumab). This data was compiled from the ongoing, single-arm, open-label, long-term extension phase 3b ALITHIOS study and from post-marketing reports submitted through the Novartis Global Safety Database.
Of the 1703 participants in ALITHIOS, 245 (14.4%) reported COVID-19, most cases were mild (44.1%) or moderate (46.5%) and the vast majority of patients had either recovered or were recovering or recovered with sequelae (98.4%).1 The overall fatal outcome (0.8%) and hospitalisation rates (9.4%) due to COVID-19 in ofatumumab-treated patients1 were lower than the rates reported in the general MS population (1.97% fatal outcome2 and 15.5%-21.5% hospitalisation2,3,4,5). Breakthrough COVID-19 infections occurred in 1.5% of fully vaccinated participants (n = 7/476), from which all recovered. No cases of COVID-19 were reported after receiving a booster vaccination (n = 27) as per the data cut-off. The current data does not suggest any evidence of increased risk of severe COVID-19 in ofatumumab-treated patients compared to the reported data from the general population or other MS patients treated with or without disease-modifying therapies (DMTs).1,2,3
Access to a range of different treatment options is important for people living with MS to manage their condition in a way that is best for them and their lifestyle. This data gives reassurance to the MS community that the risk of severe COVID-19 infection in those vaccinated is in line with that reported currently in the general population.David Martin, Chief Executive Officer, Multiple Sclerosis Trust
Dr David Paling, Consultant Neurologist at the Royal Hallamshire Hospital: “COVID-19 has had a huge impact on people living with MS and has complicated decisions about treatment. This study of the outcomes of people who developed COVID-19 whilst on ofatumumab from the ALITHIOS study will allow my colleagues and I to reassure people with MS about their risks, and have informed discussions about treatment choices based on really accurate evidence.”
Chinmay Bhatt, Managing Director, UK, Ireland & Nordics for Novartis Pharmaceuticals: “The last couple of years have been a challenge for people living with MS as they have had to make important decisions with their doctor or nurse on how best to manage their condition during the COVID-19 pandemic. At Novartis, we are committed to conducting research to understand the impact of the COVID-19 vaccines and related clinical outcomes in patients treated with our medicines to ensure no person with MS is left behind. We are very pleased with the results of this study which provide reassurance to the healthcare professionals involved in managing MS.”
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 condition.6 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 loss.7 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.8 There are three types of MS: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS).9 Patients with relapsing forms of MS (RMS) – including RRMS and SPMS with active disease – experience distinct attacks of symptoms, known as relapses.10,11 Around 85% of people are considered to have RRMS at their point of diagnosis.12 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).11,13
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 subcutaneously.14,15 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.16,17 Ofatumumab allows faster repletion of B-cells upon discontinuation versus other anti-CD20 mAbs, and therefore may offer flexibility in the management of RRMS.18
Ofatumumab has been approved for the treatment of relapsing forms of multiple sclerosis with active disease defined by clinical or imaging features in both the European Union and United Kingdom.19,20
About ALITHIOS study
The ALITHIOS study is an ongoing open-label, single-arm, multi-center extension Phase IIIb study evaluating the long-term safety, tolerability and effectiveness of ofatumumab in subjects with RMS who have participated in a Novartis ofatumumab clinical MS study. The primary endpoint is the number of patients that experience an adverse event or abnormal laboratory, vital and/or ECG results and positive suicidality outcomes. Secondary endpoints include number of relapse rates per year, 3- and 6-month confirmed disability worsening (CDW), 6-, 12- and 24-month confirmed disability improvement and improvement until end of study. This study includes a vaccination sub-study investigating the effects of ofatumumab on the development of antibody responses to selected vaccines and keyhole limpet hemocyanin (KLH) neo-antigen in subjects with RMS.21
1. Cross AH, Delgado S, Habek M, et al. COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab. Neurol Ther. 2022; https://doi.org/10.1007/s40120-022-00341-z.
2. Prosperini L, Tortorella C, Haggiag S, Ruggieri S, Galgani S, Gasperini C. Increased risk of death from COVID-19 in multiple sclerosis: a pooled analysis of observational studies. J Neurol. 2021; 1-7.
3. Barzegar M, Mirmosayyeb O, Gajarzadeh M, Afshari-Safavi A, Nehzat N, Vaheb S, et al. COVID-19 among patients with multiple sclerosis: A systematic review. Neurol Neuroimmunol Neuroinflamm. 2021;8(4):e1001.
4. Reder AT, Centonze D, Naylor ML, et al. COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies. CNS Drugs. 2021;35(3):317-330. doi:10.1007/s40263-021-00804-1
5. Möhn N, Konen FF, Pul R, et al. Experience in Multiple Sclerosis Patients with COVID-19 and Disease-Modifying Therapies: A Review of 873 Published Cases. J Clin Med. 2020;9(12):4067. Published 2020 Dec 16. doi:10.3390/jcm9124067
6. MS Society. MS in the UK. Available from: https://www.mssociety.org.uk/what-we-do/our-work/our-evidence/ms-in-the-uk [Accessed: March 2022].
7. National Multiple Sclerosis Society. Definition of MS. Available from: https://www.nationalmssociety.org/What-is-MS/Definition-of-MS [Accessed: Mar 2022]
8. NHS. Multiple sclerosis – Symptoms. Available from: https://www.nhs.uk/conditions/multiple-sclerosis/symptoms/ [Accessed: March 2022].
9. MS Society. Types of MS. Available from: https://www.mssociety.org.uk/what-is-ms/types-of-ms [Accessed: March 2022].
10. MS Society. Relapsing remitting MS. Available from: https://www.mssociety.org.uk/about-ms/types-of-ms/relapsing-remitting-ms [Accessed: March 2022].
11. National Multiple Sclerosis Society. Secondary Progressive MS (SPMS). Available from: https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Secondary-progressive-MS [Accessed: March 2022].
12. Multiple Sclerosis International Federation. Atlas of MS 2013. Available from: http://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf [Accessed: March 2022].
13. MS Society. Secondary Progressive MS (SPMS). Available from: https://www.mssociety.org.uk/about-ms/types-of-ms/secondary-progressive-ms [Accessed: March 2022].
14. Hauser S, Bar-Or A, Cohen J, et al. Ofatumumab versus teriflunomide in relapsing multiple sclerosis. N Engl J Med. 2020;383(6):546–557)
15. 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).
16. SmPC Guidance. Kesimpta® (2021) 20 mg solution for injection in pre-filled pen. Available from: https://www.medicines.org.uk/emc/product/12433/smpc#gref [Accessed: March 2022].
17. 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).
18. 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.
19. NICE Guidance. Final Appraisal Document (FAD). Ofatumumab for treating relapsing multiple sclerosis. Available from: https://www.nice.org.uk/guidance/gid-ta10557/documents/html-content-2. [Accessed March 2022].
20. EMA Medicines. Kesimpta: EPAR – Public assessment report. Kesimpta. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/kesimpta#assessment-history-section. [Accessed March 2022].
21. U.S. National Library of Medicine. Long-term safety, tolerability and effectiveness study of ofatumumab in patients with relapsing MS. https://clinicaltrials.gov/ct2/show/NCT03650114. [Accessed March 2022].