Novartis announces publication of Phase III ASCLEPIOS trials data in NEJM demonstrating efficacy of the ofatumumab in patients with relapsing multiple sclerosis.
Novartis has announced that the New England Journal of Medicine (NEJM) has published results from the ASCLEPIOS I and II studies of ofatumumab (OMB157) versus teriflunomide in adult patients with relapsing forms of multiple sclerosis (RMS). The data demonstrate the superiority of ofatumumab in reducing the rates of disease activity and progression compared with teriflunomide, a commonly prescribed oral disease modifying therapy (DMT) for relapsing multiple sclerosis1,[i]. If licensed, ofatumumab will be the first B-cell therapy that can be self-administered at home using an autoinjector pen.
In the ASCLEPIOS I and II studies, ofatumumab showed a significant reduction in the frequency of confirmed relapses versus teriflunomide, as evaluated by the annualised relapse rate (ARR)1. Results also demonstrated suppression of new inflammatory activity evidenced on MRI scans, showing a significant reduction of both gadolinium enhancing (Gd+) T1 lesions and new or enlarging T2 lesions compared with teriflunomide1.
Additionally, ofatumumab was shown to reduce the risk of three- and six-month confirmed disability worsening (CDW) compared with teriflunomide1. Gradual disability worsening independent of relapse activity is now recognised to occur throughout the course of RMS, highlighting the importance of both controlling disease activity and slowing down disability progression in the management of RMS[ii],[iii].
“It is increasingly clear that early initiation of disease modifying treatments can improve long-term outcomes for patients with RMS, and there is a need for effective, well tolerated and convenient treatment options that can be used early in the development of the condition,” said Dr Martin Duddy, Clinical Director and Consultant Neurologist at Newcastle upon Tyne Hospitals NHS Foundation Trust. “The ASCLEPIOS results are positive news for patients and physicians seeking to meaningfully reduce the chance of relapses and worsening disability.”
“Ofatumumab appears to be effective and well tolerated in the ASCLEPIOS I and II studies which support its potential to become a new treatment option that offers RMS patients flexibility and control in managing their disease,” said Dr Mark Toms, Chief Scientific Officer, Novartis UK. “These results are a testament to our commitment to reimagine treatment in the MS journey and represent another step towards addressing the unmet needs of people living with RMS in the UK.”
There are approximately 130,000 people living with MS in the UK, of which approximately 85% are considered to have relapsing remitting MS (RRMS) at the point of diagnosis[iv],[v]. Despite the availability of a range of DMTs for RMS, there are significant needs that are not fully met by current treatment options. While MS progression is different for each person and influenced by multiple factors, studies have shown that between 24% and 40% of people with RRMS progress to secondary progressive MS (SPMS) within 10 years of diagnosis[vi],[vii],[viii]. SPMS is characterised by a progressive accumulation of disability over time[ix].
A separate post-hoc analysis from the ASCLEPIOS I and II trials, presented virtually at the 6th Congress of the European Academy of Neurology (May 2020), found that ofatumumab suspended several measures of new disease activity in RMS patients2. Results showed that compared with teriflunomide, a greater proportion of patients treated with ofatumumab achieved no evidence of disease activity – as measured by NEDA-3, defined as the absence of relapses, MRI lesions, and disability worsening combined – in the first and second year of treatment2.
The marketing authorisation application for ofatumumab is currently under review by the European Medicines Agency (EMA), with decisions anticipated in Q2 2021.
[i] MS Trust. Aubagio (teriflunomide). Available at: https://www.mstrust.org.uk/a-z/aubagio-teriflunomide. Accessed July 2020.
[ii] Winkelmann A, Loebermann M, Reisinger E, Hartung H, Zettl U. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol. 2016 Apr;12(4):217-33.
[iii] The Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. Available at: http://ms-coalition.org/the-use-of-disease-modifying-therapies-in-multiple-sclerosis-updated/. Accessed July 2020.
[iv] MS Society. MS in the UK. Available at: https://www.mssociety.org.uk/what-we-do/our-work/our-evidence/ms-in-the-uk. Accessed July 2020.
[v] Multiple Sclerosis International Federation. Atlas of MS 2013. Available at: http://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf. Accessed July 2020.
[vi] Tremlett H, Yinshan Z, Devonshire V. Natural history of secondary-progressive multiple sclerosis. Mult Scler. 2008; 14: 314-324.
[vii] Scalfari A, Neuhaus A, Daumer M, Muraro PA, Ebers GC. Onset of secondary progressive phase and long-term evolution of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014;85:67-75.
[viii] Rovaris M, Confavreux C, Furlan R, Kappos L, Comi G, Filippi M. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol. 2006;5:343-354.
[ix] National Multiple Sclerosis Society. Secondary Progressive MS (SPMS). https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Secondary-progressive-MS. Accessed July 2020.