Novartis Kesimpta®six-year efficicacy data show substantial benefits in recently diagnosed treatment-na.9ve people with relapsing multiple sclerosis

• Continuous Kesimpta^®已关闭的已安装efficicacy in recently诊断（≤3years）treatment-native people living with relapsing multiple sclerosis（RMS）in an analysis of the ALITHIOS open-label extension study^1个
  
  
• Similar efficacy outcomes were demonstrated in a separate analysis of continuous Kesimpta treatment for up to six years in the overall ALITHIOS study population²
  
  
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• Treatment with Kesimpta for up to six years continues to be well tolerated with consistent safety outcomes，supporting the favorable benefit-risk profile of Kesimpta in RMS²

Basel，April172024–Novartis today announced data from the ALITHIOS open-label extension study showing sustained efficy of first-line，continuous Kesimpta^®（ofatumumumab）treatment for up to six years in recently diagnosed-defined as starting treatment within three years of initial diagnosis–treatment-naïve people living with relapsing multiple sclerosis（RMS）。^1个These efficacy outcomes included44%fewer relapses；96.4%and82.7%reductions in MRI lesions（Gd+T1 and neT2），respectively；and24.5%and21.6%fewer3-and6-month confirmed disability worsening（CDW）events，respectively，versus those who switched to Kesimpta from teriflunomide。^1个A separate analysis of the overall ALITHIOS population showed similar efficicacy with continuous Kesimpta treatment，which was also well-tolerated with a consistent safety profile up to six years。²These data will be presented at the American Academy of Neurology（AAN）2024 Annual Meeting held in Denver，Colorado and virtually on April13-182024。

“Our analysis of treatment-native people who were recently diagnosed with relapsing multiple sclerosis found that first-line use of Kesimpta for up to six years provided long-term benefits，including fewer relapses，profoundly suppressed MRI lesion activity，and fewer disability worsening events，“said principal investigabriel Pardo，M.D。，Founding Director of the Multiple Sclerosis Center of Excellence at Oklahoma Medical Research Foundation。“While measurable improvements were also seen in patients switching to Kesimpta later on，“我的天，我的天，我的天，我的天，我的天，我的天，我的天，我的天。”

“We are extremely pleased to share the new data from ALITHIOS，which adds to the growing body of evidence of Kesimpta asan efficacious and well-tolerated option for people living with RMS，”said Norman Putzki，M.D。， Development Unit Head，Neuroscience&Gene Therapy，Development，Novartis Pharmaceuticals Corporation.“Novartis committed to addressing the biggest challenges for people living with MS through relentless discovery，development，and delivery of potentially transformative medicines with the goal of achieving complete disease control.“

Study Results
In the first analysis，the low annualized relapse rate（ARR）experienced by recently diagnosed treatment-naïve（RDTN）people living with RMS receiving continuous Kesimpta during the core Phase III trials was further reduced in the ALITHIOS open-label extension study，from0.104，到0.050（，corresponding to an adjusted ARR of one relapse per20years。^1个Rates of3-and6-month progression independent of relapse activity（PIRA）with first-line Kesimpta were also lower versus switch。^1个The observed rapid increase in the proportion of participants with no evidence of disease activity（NEDA-3）with continuous first-line Kesimpta treatment was maintained up to six years。^1个

RDTN people living with RMS initially randomized to teriflunomide，improvements across several efficy outcomes were seen after switching to Kesimpta，including significant reductions in ARR（71.3%）and in MRI lesion activity（Gd+T1:98.5%reduction；neT2:93%reduction），and rapid increase in rates of NEDA-3。^1个However，rates of3-and6-month CDW events remained high er compared to patients receiving continuous Kesimpta，indicating that the efficicacy benefit of first-line Kesimpta on delaying disability worsening was not fully achieved in the switch group。^1个Across both continuous and switch groups，nine out of 10 participants achieved NEDA-3at Year6。^1个  

Similar results were seen in the second analysis，which looked at the overall ALITHIOS population。²数据showed sustained efficacy of continuous Kesimpta up to six years，including low ARR（49.9%reduction between core Phase III trials and extension phase），suppression of MRI lesion activity（Gd+T1:56.7%reduction；neT2:89.3%reduction），sustained reduction of 6-month CDW events（14.1%，relative to the switch group），lower rates of6-month PIRA，and sustained high rates of NEDA-3。²People switching from teriflunomide to Kesimpta experienced reductions in ARR（73.8%）and MRI lesion activity（Gd+T1:97.7%reduction；neT2:91.8%reduction）and a rapid increase in NEDA-3rates during the extension period。²Six-month CDW rates remained high er compared to patients receiving continuous Kesimpta，again high lighting an efficicacy benefit of first-line Kesimpta on delaying disability worsening that was not fully achieved in the switch group。²At Year6，NEDA-3 status was achieved in nine out of 10 participants in both the continuous and switch groups。²

The study also found that treatment with Kesimpta for up to six years was well-tolerated with no unexpected safety signals identified。²The rates of adverse events（AEs），serious AEs，serious infections，and malignancies remained stable with no increased risks over six years。²

The overall rates of AEs and serious AEs up to six years of Kesimpta treatment were consistent between the core Phase III trials and the ALITHIOS extension study。²The most common AEs were infections（COVID-19[34.3%]，nasopharyngitis[20.6%]，upper respiratory tract infection[14.9%]，and urinary tract infection[1.4%]）。²The incidence of serious infections remained stable over time and did not increase with Kesimpta treatment up to six years。²

Mean serum immunoglobulin G（IgG）levels remained stable up to six years of treatment and the majority of patients（97.2%）had lgG levels above the lower limit of normal（LLN）。²Mean serum immunoglobulin M（IgM）levels decreased over time but remained above the LLN for the majority of patients（65.9%）。²No clinically meaningful association was observed between IgG/IgM levels below the LLN and risk of serious infections。²

About Multiple Sclerosis
Multiple sclerosis（MS）is a chronic inflammatory disease of the central nervous system characterized by myelin destruction and axonal damage in the brain，optic nerves and spinal cord。³S，which affects around2million people worldwide，can be characterized into four main types:clinically isolated syndrome（CIS），relapsing-remitting（RRMS），secondary progressive（SPMS）and primary progressive（PPMS）。^4,5The various forms of MS can be distinguished based on whether a patient experiences relapses（clearly defined acute inflammatory attacks of worsening neurological function），and/or whether they experience progression of neurologic damage and disability from the onset of the disease。³

About Kesimpta^®（关闭）
Kesimpta is a targeted，precisely dosed and delivered B-cell therapy that provides the flexibility of self-administration for adults with relapsing forms of multiple sclerosis（RMS）。Kesimpta is the first fully human anti-CD20monoclonal antibody（mAb）self-administered by aonce-monthly injection，delivered subcutaneously（SC）in RMS。^6,7,8

The treatment regimen was designed and tested to enhance safety and tolerability and minimize the risk of systemic injection-related reactions。^6个Initial doses of Kesimpta are at Weeks0,1and2，with the first injection performed under the guidance of ahealthcare professional.Monthly Kesimpta20mg doses are associated with rapid reduction and near-complete peripheral B-cell depletion，with no significant on pharcokinetics due to duight。^6个As shown in preclinical studies，Kesimpta is thought to work by binding to a distinct epitope on the CD20molecule inducing potent B-cell lysis and depletion。⁹The selective mechanism of action and SC administration of Kesimpta allows precise delivery to the lymph nodes，where B-cell depletion in MS is needed，and preclinical studies have shown that it may preserve the B-cells in the spleen。¹⁰

数据from the ASCLEPIOS I/II core studies demonstrate Kesimpta’s efficacy and favorable safety and tolerability profile in RMS participants and the ALITHIOS open-label extension study provides additional support with up to 6years of data。^2，1120毫克/0.4 mL with an autoinjector（Sensoready）^®）also matches the preferences of many people living with MS due to its ease of use and supports patients to be compliant with，and persistent on the therapy over time。^6个Kesimpta was originally developed by Genmab and licensed to GlaxoSmithKline；Novartis obtained rights forofatumumumab from GlaxoSmithKline in all indications，including RMS，in December2015。¹²

Kesimpta has been approved for the treatment of relapsing forms of multiple sclerosis in over90countries worldwide with more than100000patients treated as of March2024。

Novartis in Neuroscience
At Novartis，in Neuroscience，we are committed to understanding and solving some of the most burdensome neurological conditions to improve the quality of life for patients and their caregivers，and to make a positive impact on society.We aim to lead the discovery， development and delivery of innovative medicines to create a transformational impact for people living with severe neurological conditions by changing the course of disease progression。

Through innovation，partnerships and community engagement，we have been tackling neurological conditions for>80years，launching transformative treatments which have made meaningful differences to millions of people worldwide.We continue to collaborate on the development of industry-leading innovativemultesciples，fors， and in the areas of neuroimmunology，neurodegeneration，and neuromuscular/rare diseases。

To ensure patients everywhere can benefit from these life-changing therapies，we work closely with key stakeholders across the world to ensure rapid access and sustainable accessibility to our medicines，with the aim of providing the best treatment choices for each person’s unique journey。

Disclaimer

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995.Forward-looking statements can generally be identified by words such as“potential，”“can，”“will，”“plan，”“may，”“could，”“would，”“expect，”“anticate”“look forward，”“believe，”“committed，”“investigational，”“pipeline，”“launch，”or similar terms，按express or implied discussions regarding potential marketing approvals，new indications or labeling for the investigational or approved products described in this press release， orregarding potential future revenues from such products.You should not place undue reliance on these statements.Such forward-looking statements are based on our current beliefs and expectations regarding future events， and are subject to significant known and unknown risks and uncertainties.Should one or more of these risks or uncertainties materialize，or should underlying assumptions prove incorrect， actual results may vary materially from those set forth in the forward-looking statements.There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market， or at any particular time.Nor can there be any guarantee that such products will be commercially successful in the future.In particular，our expectations regarding such products could be affected by，among other things，the uncertainherent in research and development， including clinical trial results and additional analysis of existing clinical data；regulatory actions or delays or government regulation generally；global trends toward health care cost containment，including government， 城市公共公共交通和reimbursement pressures and requirement为increased pricing transparency， including the effect of and efforts to mitigate pandemic diseases；safety，quality，data integrity or manufacturing issues；potential or actual data security and data privacy breaches，or disruptions of our information technology systems， and other risks and factors referred to in Novartis AG’s current Form20-F on file with the US Securities and Exchange Commission.Novartis is is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this reas ase as rease as suformation ofn，future events or otherwise。

About Novartis
Novartis is an innovative medicines company.Every day，we work to reimagine medicine to improve and extend people’s live s so that patients，healthcare professionals and societies are empowed in the face of serious disease.Our medicines reach more than250million people worldwide。

Reimagine medicine with us:Visit us athttps://www.novartis.comand connect with us onLinkedIn单击功能区上，Facebook单击功能区上，X/Twitterand，andInstagram。

参考，参考

1. Pardo G，Hauser SL，Bar-Or A，et al.Longer-term（up to 6Years）Efficacy of Ofatumumab in People with Recently Diagnosed and Treatment-Na Love Relapsing Multiple Sclerosis。Oral presentation at the American Academy of Neurology（AAN）2024 Annual Meeting；April13-182024；Denver，CO。
2. Wiendl H，Hauser SL，Nicholas J，et al.Longer-term Safety and Effficacy of Ofatumumab in People With Relapsing Multiple Sclerosis for Up to 6Years.Poster presentation at the American Academy of Neurology（AAN）2024 Annual Meeting；April13-182024；Denver，CO。
3. Guthrie EW.Multiple sclerosis:A primer and update.Add Studies Pharm.2007；4（11）：313-317。
4. Multiple Sclerosis International Federation.Atlas of MS2013-Mapping Multiple Sclerosis Around the World.Accessed August122020。http://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf
5. National MS Society.Types of MS.Access ed January182023。https://www.nationalmssociety.org/What-is-MS/Types-of-MS
6. Hauser SL，Kappos L，Bar-Or A，et al.The Development of Ofatumumab，a Fully Human Anti-CD20Monoclonal Antibody for Practical Use in Relapsing Multiple Sclerosis Treatment.Neurol Ther.2023；12（5）：1491-1515。doi:10.1007/s40120-023-00518-0
7. Kesimpta Prescribing Information.East Hanover，NJ:Novartis Pharmaceuticals Corp；September 2022。
8. 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 presentationat:ACTRIMS；February2020；West Palm Beach，FL。
9. Smith P，Kakarieka A，Wallstroem E.Ofatumumab is a fully human anti-CD20antibody achieving potent B-cell depletion through binding a distinct epitope.Poster presentation at:ECTRIMS；September 2016；London，UK。
10. Smith P，Huck C，Wegert V，et al.Low-dose，subcutaneous anti-CD20therapy effectively depletes B-cells and ameliorates CNS autoimmunity.Poster presentation at:ECTRIMS；September 2016；London，UK。
11. Cohen，JA，Hauser SL，Zielman R.，et al.Effect of Longer-term Ofatumumab Treatment on Disability Progression and Brain Volume Change.Poster presentation at:AAN；April2023；Boston，US。
12. Genmab Press Release:Genmab announces completion of agreement to transfer remaining ofatumumumab rights.December21,2015.Acceed January18203。https://ir.genmab.com/static-files/9d491b72-bb0b-4e46-a792-dee6c29aaf7d

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