An Open-label, One-arm, Proof of Concept Trial to Evaluate the Safety of ATX-MS-1467 (MSC2358825A) and Its Effect on Immune Tolerance in Subjects With Relapsing Multiple Sclerosis

This is a multi-center, open-label, single arm, baseline-controlled Phase 2a trial to evaluate the clinical and biological effects of ATX-MS-1467 in subjects with relapsing multiple sclerosis (MS) and to assess the maintenance of any such effects.

开始日期2014-02-28

申办/合作机构

Merck KGaA

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项与 ATX-MS-1467 相关的文献（医药）

2018-06-01·Neurology and therapy3区 · 医学

ATX-MS-1467 Induces Long-Term Tolerance to Myelin Basic Protein in (DR2 × Ob1)F1 Mice by Induction of IL-10-Secreting iTregs

3区 · 医学

ArticleOA

作者: Tomkinson, Blake ; Crandall, Timothy ; Dellovade, Tammy ; Choi, Ji-Kyung ; Rudin, Stefan ; Chang, Rui ; Okitsu, Shinji L ; Graham, Danielle L ; Huang, Shuning ; Mitchell, Keith ; De Souza, Adriano Luís Soares

INTRODUCTION:

Antigen-specific immunotherapy could provide a targeted approach for the treatment of multiple sclerosis that removes the need for broad-acting immunomodulatory drugs. ATX-MS-1467 is a mixture of four peptides identified as the main immune-dominant disease-associated T-cell epitopes in myelin basic protein (MBP), an autoimmune target for activated autoreactive T cells in multiple sclerosis. Previous animal studies have shown that ATX-MS-1467 treatment prevented the worsening of signs of disease in experimental autoimmune encephalitis (EAE) in the humanized (DR2 × Ob1)F1 mouse in a dose-dependent fashion.

METHODS AND RESULTS:

Our study extends these observations to show that subcutaneous treatment with 100 µg of ATX-MS-1467 after induction of EAE in the same mouse model reversed established clinical disability (p < 0.0001) and histological markers of inflammation and demyelination (p < 0.001) compared with vehicle-treated animals; furthermore, in longitudinal magnetic resonance imaging analyses, disruption of blood-brain barrier integrity was reversed, compared with vehicle-treated animals (p < 0.05). Chronic treatment with ATX-MS-1467 was associated with an enduring shift from a pro-inflammatory to a tolerogenic state in the periphery, as shown by an increase in interleukin 10 secretion, relative to interleukin 2, interleukin 17 and interferon γ, a decrease in splenocyte proliferation and an increase in interleukin 10⁺ Foxp3^- T cells in the spleen.

CONCLUSION:

Our results suggest that ATX-MS-1467 can induce splenic iTregs and long-term tolerance to MBP with the potential to partially reverse the pathology of multiple sclerosis, particularly during the early stages of the disease.

FUNDING:

EMD Serono, Inc., a business of Merck KGaA.

2018-03-13·Neurology1区 · 医学

Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis

1区 · 医学

Article

作者: Skoromets, Alexander A. ; Belova, Anna ; Maslova, Natalia N. ; Karelis, Guntis ; Martin, Keith ; Poverennova, Irina E. ; Makarov, Nikolay S. ; Chataway, Jeremy ; Barrell, Kevin ; Stolt, Pelle ; Amelina, Olga A. ; Belskaya, Galina ; Sharrack, Basil ; Trinitatskiy, Yury V. ; Fitilev, Sergey B. ; Wraith, David C. ; Stolyarov, Igor D. ; Khabirov, Farit A.

Objective:

To assess safety, tolerability, and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis using different treatment protocols to induce tolerance.

Methods:

Two open-label trials in adult participants with relapsing multiple sclerosis were conducted. Study 1 was a multicenter, phase 1b safety evaluation comparing intradermal (i.d.) (cohort 1) with subcutaneous (cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 μg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800-μg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a phase 2a, multicenter, single-arm trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 μg i.d. on day 1 to 200 μg on day 15 and 800 μg on day 29 followed by biweekly administration of 800 μg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety endpoints included treatment-emergent adverse events and injection-site reactions.

Results:

In study 1, there was a significant decrease in new/persisting T1 gadolinium-enhanced (GdE) lesions in cohort 1 from baseline to week 16, returning to baseline values at week 48. In study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies.

Conclusion:

Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post treatment. Further trials of ATX-MS-1467 are warranted.

Classification of evidence:

This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions.

2015-06-01·Neurology(R) neuroimmunology & neuroinflammation1区 · 医学

Preclinical development and first-in-human study of ATX-MS-1467 for immunotherapy of MS

1区 · 医学

ArticleOA

作者: Rigden, Rachel ; Martin, Keith F. ; Streeter, Heather B. ; Scolding, Neil J. ; Wraith, David C.

OBJECTIVE:

The study was designed to test the efficacy of ATX-MS-1467 in a relevant preclinical model and to assess its safety for the treatment of patients with secondary progressive multiple sclerosis (SPMS).

METHODS:

ATX-MS-1467 was tested for its ability to suppress experimental autoimmune encephalomyelitis (EAE) in the (Ob x DR2)F1 mouse both before and after disease onset. Safety was assessed by clinical assessment, MRI analysis, and the measurement of immune responses to self- and nonself-antigens in patients with SPMS.

RESULTS:

ATX-MS-1467 displayed a dose-dependent inhibition of EAE and was more effective than glatiramer acetate in the treatment of ongoing disease in humanized mice. A phase 1 open-label dose-escalating study demonstrated that ATX-MS-1467 was safe and well-tolerated in a group of 6 patients with SPMS, up to a dose of 800 µg.

CONCLUSIONS:

The results of this study support further development of ATX-MS-1467 in a clinical trial powered to investigate the immunologic and clinical benefits of treatment in relapsing-remitting MS.

CLASSIFICATION OF EVIDENCE:

This study provides Class IV evidence that ATX-MS-1467 is safe and tolerated in a group of 6 patients with SPMS.

项与 ATX-MS-1467 相关的新闻（医药）

2023-01-26

·PRNewswire

Myocardial Infarction (MI) Market is Projected to Grow at a Minimal CAGR of 1.61% During the Study Period (2019-2032) | Assesses DelveInsight

Considering the expected launch of new upcoming therapies and greater integration of early patient screening, it can be safely assumed that the MI market will undergo a paradigm shift in the present decade holding new prospects and opportunities for those planning to carve out their niche during the forecast period [2022–2032] LAS VEGAS, Jan. 26, 2023 /PRNewswire/ -- DelveInsight's MI Market Insights report includes a comprehensive understanding of current treatment practices, MI emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan. Key Takeaways from the MI Market Report As per DelveInsight analysis, the MI market size in the 7MM was approximately USD 21 billion in 2021 According to the assessment done by DelveInsight, the estimated total MI diagnosed prevalent cases in the 7MM was approximately 15 million in 2021 Leading MI companies such as AstraZeneca, Boehringer Ingelheim and Eli Lilly and Company, Amgen, Novartis, Idorsia Pharmaceuticals, Faraday Pharmaceuticals, CSL Behring, Immediate Therapeutics, Mitsubishi Chemical Group, Kancera, Bayer, Recardio, Mesoblast, and others are developing novel MI drugs that can be available in the MI market in the coming years The promising MI therapies in the pipeline include FARXIGA/FORXIGA (dapagliflozin), JARDIANCE (empagliflozin), Olpasiran (AMG860), Pelacarsen (TQJ230), Selatogrel, FDY-5301, CSL112, IMT-358, CL2020, MEDI6570, KAND567, Asundexian, Dutogliptin, MPC-25-IC , and others In November 2022, Amgen presented end-of-treatment data from its Phase II OCEAN (a)-DOSE study of olpasiran during the Late-Breaking Science Session of the American Heart Association (AHA) Scientific Sessions and simultaneously published in the New England Journal of Medicine As per the Q32022 investor presentation of AstraZeneca data, readouts from the Phase III (DAPA-MI) trial of FARXIGA/FORXIGA is anticipated by 2H 2023. With an estimated key regulatory submission acceptance after 2023 In June 2021, Idorsia announced the initiation of the Phase III registration study "SOS-AMI" to evaluate the efficacy and safety of self-administered SC selatogrel in suspected AMI In September 2020, the FDA granted Fast Track designation for the development of JARDIANCE to prevent hospitalization for heart failure and reduce the risk of mortality in patients with and without diabetes who have had an acute MI In July 2020, AstraZeneca was granted Fast Track designation in the US for the development of FARXIGA to reduce the risk of hospitalization for heart failure (hHF) or cardiovascular (CV) death in adults following an AMI or heart attack Discover which therapies are expected to grab the major MI market share @ MI Market Report. MI Overview MI is pathologically defined as myocardial cell death caused by prolonged ischemia. The first ultrastructural changes are diminished cellular glycogen, relaxed myofibrils, and sarcolemmal disruption, which can be seen as early as 10-15 minutes after the onset of ischemia. Symptoms of MI include chest pain, which may initially manifest as a sensation of tightness or pressure. The pain usually radiates to the left arm, but it can also radiate to the lower jaw, neck, right arm, back, and upper abdomen. Sweating, nausea, vomiting, and fainting may accompany chest pain. The typical clinical features, ECG findings, and elevation of cardiac biomarkers are used for MI diagnosis. Cardiovascular catheterization is required for definitive diagnosis and serves diagnostic and therapeutic purposes. All patients suspected of having ACS should be considered for emergency revascularization; other MI treatment options include anticoagulation, antiplatelet therapy, statin therapy, and other adjunctive measures. MI Epidemiology Segmentation DelveInsight estimates that there were approximately 15 million diagnosed prevalent cases of MI in the 7MM in 2021. Among EU4 countries, Germany had the highest number of diagnosed prevalent cases of MI, while Spain had the lowest prevalent population among the 7MM. The MI market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Diagnosed Prevalent Cases Gender-specific Prevalence Type-specific Prevalence Download the report to understand which factors are driving MI epidemiology trends @ MI Epidemiological Insights. MI Treatment Market The goals of initial MI treatment are to relieve pain, immediately identify ST changes via 12-lead EKG, initiate reperfusion (if the patient is a candidate), and assess and treat hemodynamic abnormalities. Oxygen, nitroglycerin, and morphine sulfate are the most effective pain relievers. Reperfusion therapy is indicated for patients with ST-segment elevation or a new LBBB with symptoms lasting 12 hours or less. MI treatment may be divided into two paths depending on whether the patient has a STEMI or an NSTEMI. The pharmacologic MI treatment is further subdivided into several groups of medications that improve survival, reduce recurrent ischemic events, and provide symptomatic relief. Following the primary MI treatment, a multimodal regimen of therapies is used. To classify the disease, rapid diagnostic tests and serial biomarker analysis are used to begin MI treatment. The current MI market has been segmented into different commonly used therapeutic classes based on the prevailing MI treatment pattern across the 7MM, which exhibits minor variations in the overall prescription pattern. The major classes covered in the forecast model are antiplatelet agents, anticoagulants, vasodilators, beta-blockers, lipid-lowering drugs, Angiotensin-converting enzyme (ACE) inhibitors, ARBs (Angiotensin-II receptor Blockers), and calcium channel blockers. In recent years, it has been demonstrated that pre-hospital thrombolysis has a role in the management of patients seen early after symptom onset in comparison/association with patients who had primary coronary intervention or elective primary coronary intervention. This is an important issue that is still being researched to prevent cardiac arrest, large scares, and again limit the transition to heart failure and improve the survival rate after AMI. To know more about MI treatment guidelines, visit @ MI Management. MI Pipeline Therapies and Key Companies FARXIGA/FORXIGA (dapagliflozin): AstraZeneca JARDIANCE (empagliflozin): Boehringer Ingelheim and Eli Lilly and Company Pelacarsen (TQJ230): Novartis Olpasiran: Amgen Selatogrel: Idorsia Pharmaceuticals FDY-5301: Faraday Pharmaceuticals CSL112: CSL Behring IMT-358: Immediate Therapeutics CL2020: Mitsubishi Chemical Group MEDI6570: AstraZeneca KAND567: Kancera Asundexian: Bayer Dutogliptin: Recardio MPC-25-IC: Mesoblast Learn more about the FDA-approved drugs for MI @ Drugs for MI Treatment. MI Market Dynamics The dynamics of MI market is anticipated to change in the coming years. The growing emphasis on secondary preventive measures to avoid recurrent/new events, lifestyle changes, and the growing number of smokers and cases of obesity, diabetes, hypertension, and others, are expected to fuel MI market growth. Moreover, heart attacks and strokes are major cost drivers in the 7MM healthcare system. The volume of the MI market is enormous. The patient is receiving multiple therapies at the same time. The smallest portion of the patient share can provide pharmaceutical companies with options worth millions of dollars in the MI market. However, several factors are likely to affect the growth of the MI market. Women appear to be underdiagnosed with MI, despite being at higher risk because medical training for healthcare professionals and public information has emphasized the identification of symptoms that typically affect men. This highlights the importance of gender differences in developing strategies for early MI detection and tailored secondary prevention after MI, which should result in a higher rate of MI detection in women. Moreover, off-label therapies and generics account for the majority of the current MI market because they are less expensive and more easily accessible to patients, thus, causing a dip in the MI market growth. Hence, all these factors mentioned above will hamper the MI market growth in the future. Scope of the MI Market Report Therapeutic Assessment: MI current marketed and emerging therapies MI Market Dynamics: MI market drivers and barriers Competitive Intelligence Analysis: SWOT analysis, PESTLE analysis, Porter's five forces, BCG Matrix, Market entry strategies Unmet Needs, KOL's views, Analyst's views, MI Market Access and Reimbursement Discover more about MI drugs in development @ MI Clinical Trials. Table of Contents Related Reports MI Pipeline MI Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key MI companies, including CSL Behring, Immediate Therapeutics, Mitsubishi Chemical Group, Kancera, Bayer, Recardio, among others. MI Epidemiology Forecast MI Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted MI epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Myocarditis Pipeline Myocarditis Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key myocarditis companies, including Cantargia AB, Cardiol Therapeutics, Apitope, among others. Dilated Cardiomyopathy Pipeline Dilated Cardiomyopathy Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key dilated cardiomyopathy companies, including Longeveron, Bristol Myers Squibb, Berlin Cures, Tenaya Therapeutics, Cardior Pharmaceuticals, among others. Cardiac Biomarkers Testing Market Cardiac Biomarkers Testing Market Insight, Competitive Landscape, and Market Forecast – 2027 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key cardiac biomarkers testing companies, including Beckman Coulter, Inc, Siemens Healthcare GmbH, Abbott, among others. Dilated Cardiomyopathy Epidemiology Dilated Cardiomyopathy Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical, and forecasted dilated cardiomyopathy epidemiology in the 7MM. 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It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve. Connect with us on: LinkedIn | Facebook | Twitter. Additionally, get in touch with our business executive to explore @ Healthcare Due Diligence Services. Logo - Contact Us: Shruti Thakur [email protected] +1(919)321-6187 SOURCE DelveInsight Business Research, LLP

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适应症	最高研发状态	国家/地区	公司	日期
复发性多发性硬化	临床2期	德国	Merck KGaA	2014-02-28
多发性硬化症	临床2期	-	百明信康生物技术（浙江）有限公司初创企业	-
复发-缓解型多发性硬化	临床1期	俄罗斯	Apitope Technology (Bristol) Ltd.	2010-03-01
复发-缓解型多发性硬化	临床1期	英国	Apitope Technology (Bristol) Ltd.	2010-03-01
葡萄膜炎	临床1期	-	百明信康生物技术（浙江）有限公司初创企业	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01973491 (CTgov)	临床2期	复发性多发性硬化	37	ATX-MS-1467	艱網願築鏇構選選構襯(獵窪齋鏇獵鏇齋獵鹽艱) = 顧鹹築築襯築醖範鹹選醖願廠廠範醖衊鑰衊簾 (鏇網簾遞範膚艱構衊網, 壓製築廠齋築艱蓋簾餘 ~ 蓋壓繭顧觸壓齋製範鹹) 更多	-	2017-04-13