Preapproval and postapproval evidence on drugs for multiple sclerosis

Neurology ◽  
2018 ◽  
Vol 90 (21) ◽  
pp. 964-973 ◽  
Author(s):  
Chiara Gerardi ◽  
Vittorio Bertele' ◽  
Silvia Rossi ◽  
Silvio Garattini ◽  
Rita Banzi
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Effectiveness ◽  
Dimethyl Fumarate ◽  
New Drugs ◽  
Cochrane Library ◽  
European Medicines Agency ◽  
The European Union ◽  
Disability Progression ◽  
Disease Modifying Drugs ◽  
Approved Drugs

ObjectiveTo review the evidence supporting the European Union marketing authorization of drugs for multiple sclerosis (MS) and assess how far postmarketing research addresses information gaps at the time of approval.MethodsThrough its database, we identified drugs approved by the European Medicines Agency and gathered data on pivotal trials from the European Public Assessment Reports and corresponding publications. We searched Medline, Embase, Cochrane Library, and trial registries for postmarketing randomized controlled trials testing the drugs identified in any form of the disease.ResultsSince approval of interferon and glatiramer up to 2017, the Agency has examined 10 drugs for the treatment of MS, and 8 were included in this study: alemtuzumab, daclizumab, dimethyl fumarate, fampridine, fingolimod, peginterferon-β-1a, natalizumab, and teriflunomide. We analyzed 16 pivotal trials enrolling almost 16,000 participants. Eleven compared new drugs to placebo, 5 to interferon-β-1a. Annualized relapse rate was the primary outcome in two-thirds and coprimary with disability progression in the 2 studies of alemtuzumab. Of the 52 postmarketing trials, 24 reported final results and 28 were ongoing, terminated, or completed but no results were available. None directly compared the approved drugs, thus leaving their respective therapeutic values unknown. Data on the prevention of disease progression were scarce: none of the disease-modifying drugs showed any effect on disability progression.ConclusionThe lack of comparative evidence and data on clinical effectiveness hamper the assessment of therapeutic value and place in therapy of drugs approved for MS.

Multiple Sclerosis Outcome Assessments Consortium: Genesis and initial project plan

2013 ◽  
Vol 20 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Richard A Rudick ◽  
Nicholas LaRocca ◽  
Lynn D Hudson ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Unmet Need ◽  
European Medicines Agency ◽  
Disability Progression ◽  
Consensus Approach ◽  
Disease Modifying Drugs ◽  
Outcome Assessments ◽  
Therapeutic Landscape ◽  
Measuring Outcomes ◽  
Disease Modifying

The need for improved clinical outcome measures in multiple sclerosis trials has been recognized for two decades, but only recently has the Food and Drug Administration (FDA) created a pathway for qualification of new clinician-reported outcome (ClinRO) assessments. Additionally, drug development in multiple sclerosis (MS) has been extraordinarily active, with numerous disease-modifying drugs now on the market. This shifting therapeutic landscape, along with the unmet need for drugs to treat the progressive forms of MS and the changing expectations of clinicians, patients, and payers, have led to the call for more sensitive and meaningful disability progression measures. In response to these drivers, the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was launched. A public-private partnership, MSOAC aims to accelerate the development of new therapies for MS by generating new tools for measuring outcomes in clinical trials. At the first annual MSOAC/FDA meeting, a regulatory path was outlined for qualifying a new tool for assessing efficacy in registration trials of MS. The European Medicines Agency (EMA) and FDA will provide parallel consultation and review. The consensus approach with engagement by all of the stakeholders, prominently including patients with MS, should also increase acceptance of the measure by clinicians and patients.

scholarly journals Update on recent key publications in lung oncology: picking up speed

2021 ◽  
Vol 30 (161) ◽  
pp. 200300
Author(s):  
Achim Rittmeyer ◽  
Annett Schiwitza ◽  
Lejla Sahovic ◽  
Bastian Eul ◽  
Stefan Andreas
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
New Drugs ◽  
Phase Iii ◽  
Advanced Lung Cancer ◽  
Cochrane Library ◽  
European Medicines Agency ◽  
Time Interval ◽  
The European Union ◽  
Phase Ii Trials

IntroductionAs incidence rates for lung cancer are still very high and lung cancer remains the most deadly cancer since the turn of the millennium, efforts have been made to find new approaches in cancer research. This systematic review highlights how therapeutic options were extended and how the development of new drugs has picked up speed during the last 20 years.MethodsA systematic search was performed in PubMed, Cochrane Library and the European Union Trial Register and 443 records were identified. Our inclusion criteria constituted completed phase I, II and III studies investigating drugs approved by the European Medicines Agency (EMA). Overall, 127 articles were analysed.ResultsDuring the 5 year interval from 2015 to 2020, significantly more drugs were approved after phase III, and occasionally after phase II, trials than between 2000 and 2005 (p=0.002). Furthermore, there was a significant time difference (p=0.00001) indicating an increasingly briefer time interval between the publication of phase I and phase III results in the last few years.DiscussionDue to novel therapeutic approaches, numerous new drugs in lung oncology were approved. This has improved symptoms and prognoses in patients with advanced lung cancer. However, faster approval could make it difficult to scrutinise new options regarding safety and efficacy with sufficient diligence.

scholarly journals A comparative study of teriflunomide and dimethyl fumarate within the Swedish MS Registry

2021 ◽  
pp. 135245852110196
Author(s):  
Jan Hillert ◽  
Jon A Tsai ◽  
Mona Nouhi ◽  
Anna Glaser ◽  
Tim Spelman
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Clinical Effectiveness ◽  
Dimethyl Fumarate ◽  
Population Based ◽  
Life Outcomes ◽  
Treatment Persistence ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Background: Teriflunomide and dimethyl fumarate (DMF) are first-line disease-modifying treatments for multiple sclerosis with similar labels that are used in comparable populations. Objectives: The objective of this study was to compare the effectiveness and persistence of teriflunomide and DMF in a Swedish real-world setting. Methods: All relapsing-remitting multiple sclerosis (RRMS) patients in the Swedish MS registry initiating teriflunomide or DMF were included in the analysis. The primary endpoint was treatment persistence. Propensity score matching was used to adjust comparisons for baseline confounders. Results: A total of 353 teriflunomide patients were successfully matched to 353 DMF. There was no difference in the rate of overall treatment discontinuation by treatment group across the entire observation period (hazard ratio (HR) = 1.12; 95% confidence interval (CI) = 0.91–1.39; p = 0.277; reference = teriflunomide). Annualised relapse rate (ARR) was comparable ( p = 0.237) between DMF (0.07; 95% CI = 0.05–0.10) and teriflunomide (0.09; 95% CI = 0.07–0.12). There was no difference in time to first on-treatment relapse (HR = 0.78; 95% CI = 0.50–1.21), disability progression (HR = 0.55; 95% CI = 0.27–1.12) or confirmed improvement (HR = 1.17; 95% CI = 0.57–2.36). Conclusion: This population-based real-world study reports similarities in treatment persistence, clinical effectiveness and quality of life outcomes between teriflunomide and dimethyl fumarate.

scholarly journals Risks and risk management in modern multiple sclerosis immunotherapeutic treatment

2019 ◽  
Vol 12 ◽  
pp. 175628641983657 ◽  
Author(s):  
Luisa Klotz ◽  
Joachim Havla ◽  
Nicholas Schwab ◽  
Reinhard Hohlfeld ◽  
Michael Barnett ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effect ◽  
Paradigm Shift ◽  
Mechanisms Of Action ◽  
Optimal Choice ◽  
New Drugs ◽  
Comprehensive Overview ◽  
Disease Modifying Drugs ◽  
Practical Recommendations ◽  
Target Effects

In recent years, there has been a paradigm shift in the treatment of multiple sclerosis (MS) owing to the approval of a number of new drugs with very distinct mechanisms of action. All approved disease-modifying drugs primarily work directly on the immune system. However, the identification of an ‘optimal choice’ for individual patients with regard to treatment efficacy, treatment adherence and side-effect profile has become increasingly complex including conceptual as well as practical considerations. Similarly, there are peculiarities and specific requirements with regard to treatment monitoring, especially in relation to immunosuppression, the development of secondary immune-related complications, as well as the existence of drug-specific on- and off-target effects. Both classical immunosuppression and selective immune interventions generate a spectrum of potential therapy-related complications. This article provides a comprehensive overview of available immunotherapeutics for MS and their risks, detailing individual mechanisms of action and side-effect profiles. Furthermore, practical recommendations for patients treated with modern MS immunotherapeutics are provided.

scholarly journals ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

2018 ◽  
Vol 24 (2) ◽  
pp. 96-120 ◽  
Author(s):  
Xavier Montalban ◽  
Ralf Gold ◽  
Alan J Thompson ◽  
Susana Otero-Romero ◽  
Maria Pia Amato ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pharmacological Treatment ◽  
Complex Disease ◽  
Treatment Decisions ◽  
Current Data ◽  
New Drugs ◽  
Nominal Group ◽  
Disease Modifying Drugs ◽  
Quality Of Evidence

Background: Multiple sclerosis (MS) is a complex disease with new drugs becoming available in the past years. There is a need for a reference tool compiling current data to aid professionals in treatment decisions. Objectives: To develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS. Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients–Intervention–Comparator–Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion: The present guideline will enable homogeneity of treatment decisions across Europe.

PP086 Horizon Scanning In Multiple Sclerosis Decisions In Brazil

2017 ◽  
Vol 33 (S1) ◽  
pp. 111-111
Author(s):  
Andrea Brígida de Souza ◽  
Avila Vidal ◽  
Pollyanna Gomes ◽  
Vania Canuto ◽  
Clarice Petramale
Keyword(s):  
Multiple Sclerosis ◽  
New Technologies ◽  
Grey Literature ◽  
New Drugs ◽  
European Medicines Agency ◽  
National Committee ◽  
Administration Route ◽  
Horizon Scanning ◽  
The Impact ◽  
Multiple Sclerosis Treatment

INTRODUCTION:In Brazil, the pharmaceutical sector has requested an individual incorporation in the Brazilian public health system (SUS) for each new drug for multiple sclerosis that receives sanitary authorization for marketing. Horizon Scanning within Brazilian Ministry of Health has played a key role in the recommendations made by the National Committee for Health Technology Incorporation (CONITEC). Horizon Scanning seeks to predict which technologies have potential to impact health care in SUS, before their formal request. This study aims to present the impact of horizon scanning in two assessments made by CONITEC on drugs to treat Multiple Sclerosis.METHODS:Grey literature was searched to find new and emerging drugs for multiple sclerosis treatment. Regulatory agencies were also searched: European Medicines Agency (EMA), Food and Drug Administration (FDA) and Brazilian Regulation and Health Surveillance Agency (Anvisa). A pre-defined standardized form was used. Information extracted about each drug was identified as: drugs name, mechanism of action, indication, administration route, finished phases of clinical trial and registration in other countries.RESULTS:In 2014, horizon scanning identified seven drugs while CONITEC was assessing Fingolimod for multiple sclerosis. In this case, the drug's administration route was a differential, as only three new drugs identified were also orally administrated. Thus, Fingolimod received a positive recommendation for incorporation. In 2016, horizon scanning identified fourteen drugs while Teriflunomide was under assessment. At this moment, the orally administrated Fingolimod was already available and it was identified other eight new drugs with the same route. Therefore, the initial recommendation was against its incorporation.CONCLUSIONS:Horizon scanning has proved to be of major importance for assisting recommendation-making process of the committee. In the two cases presented, horizon scanning information could predict which technologies were being developed and could be registered in Brazil. These new technologies had influenced the recommendations made by CONITEC's members. As a result, a horizon scanning section in all CONITEC's reports became mandatory.

scholarly journals Optimizing treatment strategies in paediatric, adult and late-onset multiple sclerosis

Brain ◽  
2020 ◽  
Vol 143 (10) ◽  
pp. 2866-2868
Author(s):  
Cristina Gaudioso ◽  
Robert T Naismith
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Treatment Strategies ◽  
Disability Progression ◽  
Disease Modifying Drugs ◽  
Disease Modifying ◽  
Relapsing Multiple Sclerosis

This scientific commentary refers to ‘Disease-modifying drugs can reduce disability progression in paediatric, adult and late-onset relapsing multiple sclerosis’, by Amato etal. (doi:10.1093/brain/awaa251).

Addressing the regulatory and scientific challenges in multiple sclerosis – a statement from the EU regulators

2014 ◽  
Vol 20 (10) ◽  
pp. 1282-1287 ◽  
Author(s):  
Pavel Balabanov ◽  
Manuel Haas ◽  
Andre Elferink ◽  
Serge Bakchine ◽  
Karl Broich
Keyword(s):  
Multiple Sclerosis ◽  
Drug Development ◽  
Guideline Development ◽  
New Drugs ◽  
European Medicines Agency ◽  
Guidance Document ◽  
Flexible Approach ◽  
Official Position ◽  
New Drug Development ◽  
The Eu

Improving and facilitating the process of making new drugs available to patients with multiple sclerosis (MS) requires cooperation among the regulators and other stakeholders. This cooperation will also positively contribute towards developing guidelines of the highest quality in medical, regulatory and scientific aspects. This would be beneficial both in areas that require further guideline development, but also in fields where existing guidance should be adapted to take into account evolution in science. Considering the input from all stakeholders, the European Medicines Agency confirmed its intention to update the relevant guideline and apply a flexible approach towards new drug development strategies in MS. This article is the first official position from the EU regulators, presenting the main changes to be expected in the guidance document.

scholarly journals Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012084
Author(s):  
Wei Zhen Yeh ◽  
Putu Ayu Widyastuti ◽  
Anneke Van der Walt ◽  
Jim Stankovich ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cox Regression ◽  
Dimethyl Fumarate ◽  
Disability Progression ◽  
Third Trimester ◽  
Early Postpartum ◽  
Pregnancy And Postpartum ◽  
Relapsing Remitting ◽  
Effective Option ◽  
Using Data

Objective:To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.Methods:Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses.Results:We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum.Conclusion:Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.

scholarly journals Progress in the Application of Drugs for the Treatment of Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Weipeng Wei ◽  
Denglei Ma ◽  
Lin Li ◽  
Lan Zhang
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Treatment Strategies ◽  
New Drugs ◽  
Focal Lesion ◽  
Disease Modifying Drugs ◽  
Physical Disorders ◽  
The Central Nervous System ◽  
Control Disease ◽  
New Treatment

Multiple sclerosis (MS) is an autoimmune and chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesion in CNS and cause physical disorders. Although environmental factors and susceptibility genes are reported to play a role in the pathogenesis of MS, its etiology still remains unclear. At present, there is no complete cure, but there are drugs that decelerate the progression of MS. Traditional therapies are disease-modifying drugs that control disease severity. MS drugs that are currently marketed mainly aim at the immune system; however, increasing attention is being paid to the development of new treatment strategies targeting the CNS. Further, the number of neuroprotective drugs is presently undergoing clinical trials and may prove useful for the improvement of neuronal function and survival. In this review, we have summarized the recent application of drugs used in MS treatment, mainly introducing new drugs with immunomodulatory, neuroprotective, or regenerative properties and their possible treatment strategies for MS. Additionally, we have presented Food and Drug Administration-approved MS treatment drugs and their administration methods, mechanisms of action, safety, and effectiveness, thereby evaluating their treatment efficacy.

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