DOCSLIB.ORG

RESEARCH MS UPDATE Written and Compiled by Tom Garry and Pete Kelly

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
RESEARCH MS UPDATE Written and Compiled by Tom Garry and Pete Kelly 2020 Edition RESEARCH MS UPDATE Written and compiled by Tom Garry and Pete Kelly Reviewed by Barry Hendin, MD , MS MSAA Chief Medical Officer RESEARCH Edited by Susan Courtney, UPDATE MSAA Senior Writer The Multiple Sclerosis Association of America (MSAA) is pleased to present this 2020 edition of its MS Research Update . The Update highlights important new data on approved and experimental treatments for MS, and is provided to serve as a comprehensive resource for the entire MS community. Please note that the MS Research Update focuses on research related to approved and experimental medications and therapies for the long-term treatment of multiple sclerosis. It does not include information on symptom-management medications or therapies. For additional information about MS, symptoms and symptom management, as well as MSAA’s programs and services, please visit mymsaa.org or call (800) 532-7667 . Also, please note that due to the timing of national and international MS conferences, study data from 2020 conferences generally could not be included in the Update. Information in this publication includes data presented at 2019 conferences, as well as important updates that occurred in the early months of 2020. Please visit MSAA’s website at mymsaa.org for future summaries of 2020 conference highlights. The 2020 MS Research Update is made possible through contributions in honor of: Dr. Jules Kernan and Ms. Hannah Dennehy Lee and an anonymous supporter Multiple Sclerosis Association of America National Headquarters 375 Kings Highway North Cherry Hill, New Jersey 08034 Website: mymsaa.org Toll-free phone: (800) 532-7667 Email: [email protected] CONTENTS Introduction ............................................................................................2 FDA-APPROVED MEDICATIONS: RECENTLY APPROVED Zeposia® (ozanimod) ........................................................................7 Bafiertam™ (monomethyl fumarate) ................................................9 Vumerity® (diroximel fumarate) ......................................................10 NEW DATA ON PREVIOUSLY APPROVED MEDICATIONS The Multiple Sclerosis Association of America (MSAA) is a leading INFUSED MEDICATIoNS ....................................................................13 resource for the entire MS ocrevus® (ocrelizumab) ..................................................................13 community, improving lives today Tysabri® (natalizumab)......................................................................15 through vital services and support. Lemtrada® (alemtuzumab) ..............................................................17 oRAL MEDICATIoNS ..........................................................................19 MSAA publications are intended Mayzent® (siponimod)......................................................................19 to inform and educate those with Mavenclad® (cladribine) ..................................................................21 MS and their families. MSAA does Tecfidera® (dimethyl fumarate) ......................................................22 not endorse or recommend any Aubagio® (teriflunomide) ................................................................24 specific products, services, Gilenya® (fingolimod) ......................................................................25 therapies, or activities mentioned in articles or advertisements that INJECTABLE MEDICATIoNS ..............................................................27 appear in MSAA publications. Rebif® (interferon beta-1a) ..............................................................27 MSAA, its staff, and those affiliated Plegridy® (peginterferon beta-1a) ..................................................27 with the writing of this publication cannot be held responsible for EXPERIMENTAL MEDICATIONS any unintentional errors. MoNoCLoNAL ANTIBoDIES............................................................29 ofatumumab......................................................................................29 MSAA strives to provide useful, Ublituximab........................................................................................30 up-to-date information on matters opicinumab ......................................................................................31 of concern to MS patients and Rituxan® (rituximab)..........................................................................32 their families. This material is Temelimab ........................................................................................33 intended for general informational purposes only, and it does not S1P RECEPToR MoDULAToRS ........................................................34 constitute medical advice. You Ponesimod ........................................................................................34 should not use the information presented as a means of ADMINISTERED oRALLY ....................................................................35 diagnosis or for determining Evobrutinib ........................................................................................35 treatment. For diagnosis and Ibudilast (also known as MN-166) ..................................................35 CNM-Au8 ..........................................................................................36 treatment options, you are urged MD1003..............................................................................................37 to consult your physician. NEW DIRECTIONS IN MS RESEARCH Copyright © Multiple Sclerosis Association of America, 2020. All Stem Cell Therapies ..........................................................................38 rights reserved. No part of this Diet and MS ......................................................................................41 publication may be reproduced, Gut Microbiome ................................................................................43 stored in a retrieval system, or Vitamin D............................................................................................45 transmitted in any form or by any Biomarkers ........................................................................................46 Genetics..............................................................................................47 means, electronic, mechanical, photocopying, recording, or Closing Notes ......................................................................................50 otherwise, without prior written permission from MSAA. References ............................................................................................51 Multiple Sclerosis Association of America 1 MS RESEARCH UPDATE 2020 MS RESEARCH UPDATE Introduction report. Rather, the items presented here were selected for their relevance to current or The 2020 MS Research Update reviews future patient care, and with a view toward new data and findings on: showcasing the breadth of work being done • Disease-modifying therapies (DMTs) to understand and treat MS. The information approved by the FDA, including recently that follows is drawn from a variety of sources, approved medications and those that have including journal literature on MS and its been available for several years management, a review of ongoing clinical • Experimental drugs under investigation trials, and presentations at major national for the long-term treatment of multiple and international conferences. sclerosis (MS) Please note that this MS Research Update reports on the most recent study • New therapeutic approaches and treatment results available at the time of publication. targets, such as stem cell therapy and the While every effort has been made to provide gut microbiome meaningful, timely, and balanced information, • Promising areas of inquiry that are keeping the amount of information equal for enhancing researchers’ and clinicians’ each medication covered is not possible. understanding of MS, such as genetics and Please understand that the different degree biomarkers of coverage given to the various therapies While this 2020 edition of MSAA’s MS should in no way be considered as favoritism Research Update provides a comprehensive toward any one medication or treatment overview of important areas of inquiry and approach. Additionally, references have been study findings, it is not an exhaustive cited only for newer study results. compilation of all relevant data released in the While medications for management of MS past year. There is – fortunately – far too much symptoms are beyond the scope of this ongoing research for summation in a single report, information on the specific symptoms Multiple Sclerosis Association of America 2 MS RESEARCH UPDATE 2020 INTRODUCTION of MS and their treatment is available in the biotechnology company investigating the symptoms section of MSAA’s website. monoclonal antibody temelimab for use in Providing these resources is at the heart of primary- and secondary-progressive MS, in MSAA’s mission of being a leading resource March announced the postponement of a for the entire MS community, improving lives planned Phase II trial of the medication in today through vital services and support. order to “prioritize healthcare resources Feedback and thoughts on the 2020 MS behind the fight of CoVID-19 and to reduce Research Update are welcomed. These can the risk for MS patients.” 1 Meanwhile, be directed to MSAA at [email protected] . MediciNova, the company developing the oral medication ibudilast for potential
Load more

Recommended publications
  • 211855Orig1s000
    &(17(5)25'58*(9$/8$7,21$1' 5(6($5&+ APPLICATION NUMBER: 2ULJV 6800$5<5(9,(: Summary Memorandum for Regulato1y Action Summary Memorandum for Regulatory Action Date October 11, 2019 Paul Lee, MD, PhD From Nick Kozauer, MD Subject Summary Memorandum for Regulatory Action NDA/BLA # and Supplement# NDA 211855 under 505(b)(2)1 Applicant Alkermes Date of Submission December 13, 2018 PDUFA Goal Date October 13, 2019 Proprietary Name Vun1erity Established or Proper Name Diroximel fumarate Dosage Form(s) 231 mg delayed release capsules Applicant Proposed VUMERITY is indicated for the treatment of adult patients Indication(s)/Population(s) with relapsing forms of multiple sclerosis The starting dose for VUMERITY is 231 mg twice a day Applicant Proposed Dosing orally. After 7 days, the dose should be increased to 462 Regimen(s) mg (two 231 mg capsules) twice daily orally. Recommendation on Tentative Approval Regulatory Action VUMERITY is indicated for the treatment of adult patients Recommended with relapsing forms of multiple sclerosis (MS), to include Indication(s)/Population(s) (if clinically isolated syndrome, relapsing-remitting disease, applicable) and active secondary progressive d isease, in adults Recommended Dosing Same as proposed Recimen(s) (if applicable) 1The referenced dmg for this 505(b)(2) application is Tecfidera (NDA 204063) Reference ID: 4504909 Summary Memorandum for Regulatory Action 1. Benefit-Risk Assessment The application provides an adequate bridge to Tecfidera, the referenced product for this 505(b)(2) application. Therefore, the previous findings of safety and effectiveness for Tecfidera also apply to Vumerity. 2. Background The applicant seeks approval of Vumerity (diroximel fumarate) using the 505(b)(2) regulatory pathway for monomethyl fumarate (MMF), relying on the previous findings of safety and effectiveness for Tecfidera (dimethyl fumarate [DMF]).
    [Show full text]
  • Oral MS Disease-Modifying Therapies C21142-A
    Drug and Biologic Coverage Criteria Effective Date: 05/01/2019 Last P&T Approval/Version: 07/28/2021 Next Review Due By: 08/2022 Policy Number: C21142-A Oral MS Disease-Modifying Therapies PRODUCTS AFFECTED Mayzent (siponimod), Aubagio (teriflunomide), Gilenya (fingolimod), Mavenclad (cladribine), Tecfidera (dimethyl fumarate), Vumerity (diroximel fumarate), Bafiertam (monomethyl fumarate),dimethyl fumarate, Zeposia (ozanimod), Ponvory (ponesimod) COVERAGE POLICY Coverage for services, procedures, medical devices, and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide Molina Healthcare complete medical rationale when requesting any exceptions to these guidelines Documentation Requirements: Molina Healthcare reserves the right to require that additional documentation be made available as part of its coverage determination; quality improvement; and fraud; waste and abuse prevention processes. Documentation required may include, but is not limited to, patient records, test results and credentials of the provider ordering or performing a drug or service. Molina Healthcare may deny reimbursement or take additional appropriate action if the documentation provided does not support the initial determination that the drugs or services were medically necessary, not investigational or experimental, and otherwise within the scope of benefits afforded to the member, and/or the documentation demonstrates a pattern of billing or other practice that is inappropriate or excessive DIAGNOSIS: Multiple Sclerosis REQUIRED MEDICAL INFORMATION: A.
    [Show full text]
  • Multiple Sclerosis
    bmchp.org | 888-566-0008 wellsense.org | 877-957-1300 Pharmacy Policy Multiple Sclerosis Policy Number: 9.212 Version Number: 2.0 Version Effective Date: 6/1/2021 Product Applicability All Plan+ Products Well Sense Health Plan Boston Medical Center HealthNet Plan New Hampshire Medicaid MassHealth ACO NH Health Protection Program MassHealth MCO Qualified Health Plans/ConnectorCare/Employer Choice Direct Senior Care Options Note: Disclaimer and audit information is located at the end of this document. Prior Authorization Policy Products Affected: Aubagio (teriflunomide) Kesimpta (ofatumumab) Avonex pen (interferon beta-1a) Mayzent (siponimod) Betaseron (interferon beta-1b) Plegridy (peginterferon beta-1a) Dalfampridine ER Rebif (interferon beta-1a) Dimethyl fumarate Tecfidera (dimethyl fumarate) (NF) Gilenya (fingolimod) Vumerity (diroximel fumarate) Glatiramer Zeposia (ozanimod) The Plan may authorize coverage of the above product(s) for members meeting the following criteria: Avonex, Betaseron, glatiramer, Plegridy, Rebif Initial Criteria 1. Member is 18 years of age and older; AND NF = non-formulary + Plan refers to Boston Medical Center Health Plan, Inc. and its affiliates and subsidiaries offering health coverage plans to enrolled members. The Plan operates in Massachusetts under the trade name Boston Medical Center HealthNet Plan and in other states under the trade name Well Sense Health Plan. Multiple Scerlosis 2. Diagnosis of relapsing multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease; AND 3. Prescribed by or in consultation with a neurologist; AND 4. Will not be used in combination with another MS disease modifying agent; AND 5. Will not be given concurrently with live vaccines; AND 6.
    [Show full text]
  • Prior Authorization Multiple Sclerosis – Ponvory™ (Ponesimod Tablets)
    Cigna National Formulary Coverage Policy Prior Authorization Multiple Sclerosis – Ponvory™ (ponesimod tablets) Table of Contents Product Identifier(s) National Formulary Medical Necessity ................ 1 79750 Conditions Not Covered....................................... 2 Background .......................................................... 2 References .......................................................... 2 Revision History ................................................... 2 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation.
    [Show full text]
  • 5948 6 March 2020 Freedom of Information Request I Am Writing In
    Trust Headquarters East Surrey Hospital Canada Avenue Redhill RH1 5RH Tel: 01737 768511 www.surreyandsussex.nhs.uk Our ref: 5948 6 March 2020 Freedom of information request I am writing in response to your request for information which has been handled under the Freedom of Information Act 2000 (FOIA). Could you please provide us with the numbers of patients in relation to the questions mentioned below, for a period of last 12 months: We do not record the number of patients who have attended the trust who have a diagnosis on MS 1. In your trust how many patients have a diagnosis of Multiple Sclerosis (MS), regardless of whether they are currently on treatment? We only record the number of patients who have attended the trust who have a diagnosis but we are unable to tell if they were diagnosed for the first time within this admission. 2. Of these MS patients, how many have been diagnosed with relapsing (RRMS), primary progressive (PPMS) or secondary progressive (SPMS) MS; See above If you do not code your MS patients in this way, do you have plans to do this? RRMS PPMS SPMS Not known 3. How many patients with Multiple Sclerosis have been treated with disease modifying drugs in the past 6 months. Please include all patients whose treatment is ongoing, even those with infrequent dosing schedules (e.g. Lemtrada, Mavenclad, Ocrevus). Please provide the total number of patients by treatment for the following disease modifying drugs: See question 5 below. Aubagio (teriflunomide) Avonex (interferon beta-1a) Betaferon (interferon beta-1b) Brabio (glatiramer acetate) Copaxone (glatiramer acetate) Extavia (beta interferon-1b) Gilenya (fingolimod) Lemtrada (alemtuzumab) Mavenclad (cladribine) Mayzent (siponimod) Ocrevus (ocrelizumab) Plegridy (peginterferon beta-1a) Rebif (beta interferon-1a) Tecfidera (dimethyl fumarate) Tysabri (natalizumab) Vumerity (diroximel fumarate) Zinbryta (daclizumab) Ampyra (fampyra) Ozanimod 4.
    [Show full text]
  • Timeline of Progress in MS Research
    Timeline of Progress in MS Research This timeline highlights a selection of major landmarks in research into multiple sclerosis and the launch of programs to propel this research forward. These are only a few of thousands of advances in basic and clinical research that have laid the foundation for the rapid progress we’re seeing today. 1421 First documented case of MS; St. Lidwina of Schiedam 1860-70 First studies of myelin and glial cells in brain tissue 1868 First correlation of MS clinical symptoms with central nervous system pathology; disease named "Sclerose en plaques" by Jean Martin Charcot 1869 First attempts to treat MS with gold chloride, zinc, sulfate, silver nitrate, strychnine and electrical stimulation (by Charcot) 1928 Discovery that myelin is produced by oligodendrocyte glial cells 1933 Acute experimental allergic encephalomyelitis (EAE) developed as model for MS 1936 Discovery that lymphocytes are involved in immune function 1943 First detailed description of the composition of myelin 1946 National MS Society USA Launched 1947 First research grant to Elvin A. Kabat, MD 1950 National Institute of Neurological Diseases founded at National Institutes of Health through the work of the Society 1950 Society funds first major survey of MS in the U.S. and Canada 1954 First Fellowship programs to train MS Scientists offered 1965 Society-convened panel of experts develops precise criteria for diagnosing MS 1969 Society co-funds research of steroid ACTH, which becomes the first drug shown to speed recovery from MS relapses 1974
    [Show full text]
  • Ponesimod (Ponvory) Reference Number: ERX.SPA.437 Effective Date: 06.01.21 Last Review Date: 05.21 Line of Business: Commercial, Medicaid Revision Log
    Clinical Policy: Ponesimod (Ponvory) Reference Number: ERX.SPA.437 Effective Date: 06.01.21 Last Review Date: 05.21 Line of Business: Commercial, Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Ponesimod (Ponvory™) is a sphingosine 1-phosphate receptor modulator. FDA Approved Indication(s) Ponvory is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. Health plan approved formularies should be reviewed for all coverage determinations. Requirements to use preferred alternative agents apply only when such requirements align with the health plan approved formulary. It is the policy of health plans affiliated with Envolve Pharmacy Solutions™ that Ponvory is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Multiple Sclerosis (must meet all): 1. Diagnosis of one of the following (a, b, or c): a. Clinically isolated syndrome, and member is contraindicated to all, or has experienced clinically significant adverse effects to two, of the following: Aubagio®, glatiramer (Copaxone®, Glatopa®), an interferon-beta agent (Betaseron® or Rebif®); b. Relapsing-remitting MS, and failure of two of the following, unless clinically significant adverse effects are experienced or all are contraindicated: Aubagio®, dimethyl fumarate, Gilenya®, glatiramer (Copaxone®, Glatopa®), an interferon-beta agent (Betaseron® or Rebif®), Kesimpta®, Mayzent®, Ocrevus®, Tysabri®, Vumerity®, Zeposia®;* *Prior authorization is required for all disease modifying therapies for MS.
    [Show full text]
  • Multiple Sclerosis Disease Modifying Therapy
    Neuro-Pharmacology Immuno-modulatory Therapy MULTIPLE SCLEROSIS DISEASE MODIFYING THERAPY Drug Indic Dose Effect Side effects Monitoring Self Injectables IFB 1A Avonex 1996 RRMS 30mic IM weekly Modulates T-cell and B-cell Flu-like symptoms, headaches HGB, WBC, LFTs IFB 1A Rebif 1998 RRMS 44mic SQ MWF function. Down regulates Leukopenia, anemia, depression, suicide TSH/Free T4 IFB 1A Plegridy 2014 RRMS 125mic SQ q2w inflammatory cytokines and T-cells Hepatotoxicity, Thyroid dysfunction Risk for Depression Injection site necrosis with SQ inj IFB 1B Betaseron, RRMS 250mic SQ EOD ↓Relapses = 30% Neutralizing antibodies, Pregnancy Class: C Extavia, 2009 ↓CIS to CDMS = 50% Washout 1 month Glatiramer acetate RRMS 20mg SQ daily or Injection site pain & lipoatrophy Copaxone 1997 40mg SQ MWF Post-injection reactions: (chest/neck tightness Glatopa 2015 tachycardia, diaphoresis, dyspnea, anxiety) No Washout needed Daclizumab RRMS 150mg SC CD25 blocker (IL-2 receptor) Withdrawn from market after patients . Zinbryta, 2016 monthly developed fulminant hepatitis Withdrawn in 2017 Oral Fingolimod RRMS 0.5 mg daily Sphingosine-1-phosphate Bradyarrhythmia, AV block Pre-screen: Gilenya, 2010 receptor modulator. Macular edema - PRES CBC, EKG, LFT, VZV IgG Peripheral T-cell sequestration in Pulmonary function worsening (vaccinate if negative) lymph nodes Lymphopenia & PML - Transaminitis 1st dose monitoring (can be Varicella meningoencephalitis done at home). ↓Relapses = 54% Malignancy risk Then: ↓EDSS = 30% Pregnancy Class: C CBC/LFT’s q6m, fundus at 6m ↓MRI = 74% (T2), 82% (Gd) Washout 2 month (t1/2 is one week) Beware of PML & malignancy Siponimod RRMS 2 mg daily Sphingosine-1-phosphate Bradyarrhythmia, AV block Pre-screen: Mayzent, 2018 SPMS (requires receptor modulator, specific to Macular edema in 1.8% CYP2C9 testing (don’t use in titration) subtype 1&5, sparing subtype 3 Pulmonary function worsening patients with CYP2C9 3/3) (less cardiac side effects).
    [Show full text]
  • Glatopa™ (Glatiramer Acetate)
    UnitedHealthcare Pharmacy Clinical Pharmacy Programs Program Number 2021 P 1064-14 Program Prior Authorization/Notification Medication Multiple Sclerosis - Aubagio® (teriflunomide), Avonex® (interferon β-1a), Bafiertam™ (monomethyl fumarate), Betaseron® (interferon β-1b), Copaxone® (glatiramer acetate)*, dimethyl fumarate, Extavia® (interferon β-1b)*, Gilenya® (fingolimod), Glatopa™ (glatiramer acetate)*, glatiramer acetate, Kesimpta (ofatumumab), Mayzent (siponimod)®, Plegridy™ (peginterferon β-1a), Rebif® (interferon β-1a), Tecfidera™ (dimethyl fumarate)*, Vumerity™ (diroximel fumarate)*, Zeposia (ozanimod) ® *Copaxone (brand), Extavia, Glatopa, Tecfidera (brand), and Vumerity are excluded from coverage for the majority of our benefits. Mavenclad® (cladribine) coverage is provided according to the product specific Mavenclad Prior Authorization/Notification program P&T Approval Date 5/2011, 5/2012, 11/2012, 07/2013, 08/2013, 5/2014, 10/2014, 10/2015, 10/2016, 10/2017, 2/2018, 2/2019, 5/2019, 10/2019, 1/2020, 11/2020, 1/2021 Effective Date 4/1/2021; Oxford only: 4/1/2021 1. Background Avonex® and Rebif® (interferon β-1a), Betaseron® and Extavia® (interferon β-1b), Plegridy™ (peginterferon β-1a), Copaxone® and Glatopa™ (glatiramer acetate), Aubagio® (teriflunomide), Mayzent® (siponimod), Tecfidera™ (dimethyl fumarate), Bafiertam (monomethyl fumarate), Zeposia (ozanimod), Kesimpta (ofatumumab), and Vumerity™ (diroximel fumarate) are indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated
    [Show full text]
  • Prior Authorization Multiple Sclerosis – Aubagio® (Teriflunomide Tablets)
    Cigna National Formulary Coverage Policy Prior Authorization Multiple Sclerosis – Aubagio® (teriflunomide tablets) Table of Contents Product Identifier(s) National Formulary Medical Necessity ................ 1 70087 Conditions Not Covered....................................... 2 Background .......................................................... 2 References .......................................................... 3 Revision History ................................................... 3 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation.
    [Show full text]
  • 211855Orig1s000
    &(17(5)25'58*(9$/8$7,21$1' 5(6($5&+ APPLICATION NUMBER: 2ULJV 27+(55(9,(: 6 Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research | Office of Surveillance and Epidemiology (OSE) Epidemiology: ARIA Sufficiency Templates Version: 2018-01-24 Date: October 31, 2019 Reviewer: Sara Karami, Ph.D., M.P.H Division of Epidemiology I Team Leader: Kira Leishear, Ph.D., M.S. Division of Epidemiology I Deputy Division Director: CAPT Sukhminder K. Sandhu, Ph.D., M.S., M.P.H. Division of Epidemiology I Subject: ARIA Sufficiency Memo for Pregnancy Safety Concerns Drug Name: Vumerity™ (diroximel fumarate) Application Type/Number: NDA 211855 Applicant/sponsor: Alkermes, Inc. OSE RCM #: 2019-2149 Page 1 of 8 Reference ID: 4514067 Expedited ARIA Sufficiency Template for Pregnancy Safety Concerns 1. BACKGROUND INFORMATION 1.1. Medical Product Diroximel fumarate (Vumerity™) is a delayed-release medication for the treatment of relapsing forms of multiple sclerosis (RMS) in adults. After oral administration, diroximel fumarate is presystemically hydrolyzed by intestinal esterases into monomethyl fumarate (MMF) and 2- hyroxyethyl succinimide (HES), a major inactive metabolite. Subsequently, both MMF and HES are absorbed by the small intestine. While the exact therapeutic mechanism of diroximel fumarate on RMS is unknown, MMF is the primary and only known active metabolite of dimethyl fumarate (DMF, Tecfidera), which was approved for RMS treatment in 2013. Because diroximel fumarate is not quantifiable
    [Show full text]
  • Gudesblatt M,1 Wray S,2 Miller C,3 Hanna J,4 Lopez-Bresnahan M,5
    DXT42 Efficacy of Diroximel Fumarate in Relapsing-Remitting MS Patients Who Are Newly Diagnosed or Previously Treated With Interferons or Glatiramer Acetate Gudesblatt M,1 Wray S,2 Miller C,3 Hanna J,4 Lopez-Bresnahan M,5 Kandinov B,5 Chen H,3 Yang L,3 Leigh-Pemberton R5 1South Shore Neurologic Associates, PC, Patchogue, NY, USA; 2Hope Neurology Multiple Sclerosis Center, Knoxville, TN, USA; 3Biogen, Cambridge, MA, USA; 4Biogen, Maidenhead, UK; 5Alkermes, Waltham, MA, USA Figure 1. EVOLVE-MS-1 Study Design Table. Baseline Demographics and Disease Characteristics in EVOLVE-MS-1 Conclusions Overall Newly Diagnosed Prior IFN/GA Screeninga DRF 462 mg BID (96 weeks, open label) Follow-upb Population Subgroup Subgroup • In newly diagnosed and prior IFN/GA patients treated with DRF for a median of ~1 year, DRF demonstrated improvement from n = 696 n = 82 n = 361 baseline in clinical and radiological measures of disease activity. Mean (SD) age, y 41.9 (11.0) 37.1 (11.3) 43.7 (10.6) – Significant reductions were observed in ARR, and more patients were relapse free compared with baseline. Study – Patients had significantly fewer Gd+ lesions compared with baseline. week –4 12 4812 16 20 24 36 48 60 72 84 96 98 Female, n (%) 505 (73) 54 (66) 276 (77) – Outcomes in newly diagnosed and prior IFN/GA patients were similar to those observed in the overall EVOLVE-MS-1 study population. US region, n (%) 283 (41) 30 (37) 197 (55) • DRF may be an effective treatment option in patients who are newly diagnosed with MS and DMT naive, as well as in those with BID = twice daily; DRF = diroximel fumarate aThe EVOLVE-MS-1 study population includes patients who rolled over from the randomized, double-blind, Phase 3 EVOLVE-MS-2 (NCT03093324) study after a greater time since diagnosis and prior IFN or GA use.
    [Show full text]