Post hoc analysis from Phase III ASCLEPIOS trials showed superiority of ofatumumab versus teriflunomide in clinical measures of disease activity and in slowing disability worsening in newly diagnosed, treatment-naïve relapsing multiple sclerosis (RMS) patients1
Increased understanding of ofatumumab's safety profile with additional safety data representing over 2,000 patient years of exposure2
If approved in the UK, ofatumumab would be the first and only targeted B-cell therapy for patients with RMS that can be self-administered
London, UK, September 11, 2020 - Novartis announced today that new data on ofatumumab from the Phase III ASCLEPIOS and ALITHIOS trials and the Phase II APLIOS trial were presented at MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting (September 11-13, 2020). This new data adds to the growing body of evidence on the effectiveness and safety profile of ofatumumab, a targeted B-cell therapy that can be self-administered, and its potential to become a treatment option for people with relapsing forms of multiple sclerosis (RMS).
A post hoc analysis from the Phase III ASCLEPIOS I and II trials evaluated the efficacy and safety of ofatumumab versus teriflunomide in a sub-group of newly diagnosed (within 3 years before screening), treatment-naïve (no prior disease modifying treatment use) RMS patients1. Consistent with the overall study population results, the analysis showed patients treated with ofatumumab experienced less frequent relapses, reduced inflammatory activity (evidenced by MRI scans), and prolonged time to disability worsening compared to those who received teriflunomide1.
“Early treatment intervention with a well-tolerated and effective disease modifying therapy is important to improve long-term outcomes for patients with RMS,” said Dr Waqar Rashid, Consultant Neurologist at St George’s University Hospitals NHS Foundation Trust. “Building on previous ASCLEPIOS data, the results of this subgroup analysis show that ofatumumab is potentially a viable treatment option to reduce disease activity and slow disability worsening for people newly diagnosed with RMS.”
Results from a separate extended analysis of the ongoing Phase IIIb ALITHIOS trial on the long-term safety of ofatumumab in adults with RMS were also reported2. The ALITHIOS trial includes patients who continued on ofatumumab treatment from the Phase III ASCLEPIOS trials or the Phase II APLIOS trial (median duration of ofatumumab treatment: 21 months), and newly-switched patients who received teriflunomide in ASCLEPIOS and switched to ofatumumab in ALITHIOS (median duration of ofatumumab treatment: 4.4 months)2. The results showed no new safety signals, highlighting that the safety profile of ofatumumab in RMS patients remains consistent with data reported in the core studies2.
Additional data from the Phase III ASCLEPIOS trials demonstrated a prognostic value of baseline serum neurofilament light chain (NfL) levels for on-study disease activity and worsening in RMS patients, including newly diagnosed, treatment-naïve patients3. These results suggest that NfL levels, a marker of disease activity and treatment response, may supplement clinical assessments, including MRI, for standard monitoring, helping to identify patients who are at high risk for future disease activity3.
“The new data adds to the body of evidence that show ofatumumab has the potential to be used early in the course of RMS,” said Dr Samin Saeed, ad interim Chief Scientific Officer, Novartis UK. “The fact that it can be self-administered at home should offer RMS patients flexibility and independence in managing their condition, and we are proud to be advancing innovative treatments that aim to positively impact people living with MS.”
The marketing authorisation application for ofatumumab is currently under review by the European Medicines Agency (EMA), with decisions anticipated in Q2 2021. In August 2020, the US Food and Drug Administration approved ofatumumab (Kesimpta®) as an injection for subcutaneous use for the treatment of RMS, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
About ASCLEPIOS I and II studies
The ASCLEPIOS I and II studies are twin, identical design, flexible duration (up to 30 months), double-blind, randomized, multi-centre Phase III trials evaluating the safety and efficacy of ofatumumab versus teriflunomide in adults with RMS4. 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 5.54. Ofatumumab demonstrated a significant reduction in annualized 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; primary endpoint)4.
A separate post hoc analysis from the ASCLEPIOS I and II trials evaluated the efficacy and safety of ofatumumab in a subgroup of newly diagnosed (within three years before screening), treatment-naïve RMS patients (n=615)1. Results showed that ofatumumab significantly reduced the ARR by 50.3% (0.09 vs 0.18; P<0.001) compared with teriflunomide1. Ofatumumab significantly reduced the mean number of Gd+ T1 lesions by 95.4% (0.02 vs 0.39; P<0.001) and new or enlarging T2 lesions by 82.0% (0.86 vs 4.78; P<0.001) compared with teriflunomide1.
About ALITHIOS study
The ALITHIOS study is an ongoing, open-label, single arm, multi-centre extension Phase IIIb study evaluating the long-term safety, tolerability and effectiveness of ofatumumab in patients with RMS who have participated in prior ofatumumab studies. 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 relapses per year, 3- and 6-month CDW, 6-, 12- and 24-month confirmed disability improvement and improvement until end of study.
About APLIOS study
The APLIOS study is a 12-week, open-label, Phase II bioequivalence study to determine the onset of B-cell depletion with ofatumumab subcutaneous monthly injections and the bioequivalence of subcutaneous administration of ofatumumab via a prefilled syringe—as used in ASCLEPIOS I and II—and a Sensoready® autoinjector pen in patients with RMS.
About ofatumumab (OMB157)
Ofatumumab is a fully human anti-CD20 monoclonal antibody (mAb) in development for RMS that is self-administered by a once-monthly injection, delivered subcutaneously4,6. 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 depletion5. Once-monthly dosing of ofatumumab allows faster repletion of B-cells versus other anti-CD20 monoclonal antibodies, and therefore may offer flexibility in the management of RMS6.
About Multiple Sclerosis There are approximately 130,000 people with multiple sclerosis (MS) in the UK, and each year around 7,000 people are newly diagnosed with the condition7. 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 loss8. 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)9. There are three types of MS: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)10. Patients with relapsing forms of MS – including RRMS and SPMS with active disease – experience distinct attacks of symptoms, known as relapses11,12. Around 85% of people are considered to have RRMS at their point of diagnosis13. 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 MRI activity) or not active (no evidence of current activity)11,14.
About Novartis in Multiple Sclerosis
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 multiple sclerosis (MS) portfolio includes Gilenya®▼ (fingolimod, an S1P modulator), which is licenced in Europe for the treatment of adults and children aged 10 and older with highly active relapsing remitting forms of MS. Mayzent®▼ (siponimod) is licenced in Europe for the treatment of adult patients with SPMS with active disease evidenced by relapses or imaging features of inflammatory activity. Extavia® (interferon beta-1b for subcutaneous injection) is approved in Europe to treat people with RRMS, people with SPMS with active disease (evidenced by relapses), and people who have had a single clinical event suggestive of MS.
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. Find out more at www.novartis.com.
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.
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 Gärtner J, Hauser SL, Bar-Or A, et al. Benefit-risk of ofatumumab in treatment-naïve early relapsing multiple sclerosis patients. ePoster presentation at MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting; September 2020
 Cross AH, Fox E, De Seze J, et al. Safety experience with extended exposure to ofatumumab in patients with relapsing multiple sclerosis from Phase 2 and 3 clinical trials. ePoster presentation at MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting; September 2020
 Kuhle J, Kappos L, Cross AH, et al. Baseline serum neurofilament light levels have prognostic value for on-study MRI activity: Results from ASCLEPIOS trials. ePoster presentation at MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting; September 2020
 Hauser S, Bar-Or A, Cohen J, et al. Ofatumumab versus teriflunomide in relapsing multiple sclerosis. New Engl J Med. 2020;383:546-57.
 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; 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.