DOCSLIB.ORG

Utah Medicaid Pharmacy and Therapeutics Committee Drug

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Utah Medicaid Pharmacy and Therapeutics Committee Drug Utah Medicaid Pharmacy and Therapeutics Committee Drug Class Review Agents for the Treatment of Multiple Sclerosis Oral Medications: Cladribine (Mavenclad) Dalfampridine (Ampyra, generic) Dimethyl fumarate (Tecfidera) Diroximel fumarate (Vumerity) Fingolimod (Gilenya) Siponimod (Mayzent) Teriflunomide (Aubagio) Subcutaneous and Intramuscular Medications: Glatiramer acetate (Copaxone, Glatopa, generic) Interferon beta-1a (Avonex, Rebif) Interferon beta-1b (Betaseron, Extavia) Peginterferon beta-1a (Plegridy) Intravenous Medications: Alemtuzumab (Lemtrada) Mitoxantrone (generic) Natalizumab (Tysabri) Ocrelizumab (Ocrevus) Report finalized October 2019 Report presented November 2019 Review prepared by: Elena Martinez Alonso, B.Pharm., MSc MTSI, Medical Writer Lauren Heath, Pharm.D., MS, BCACP, Assistant Professor (Clinical) Valerie Gonzales, Pharm.D., Clinical Pharmacist Vicki Frydrych, B.Pharm., Pharm.D., Clinical Pharmacist Joanne LaFleur, PharmD, MSPH, Associate Professor University of Utah College of Pharmacy University of Utah College of Pharmacy, Drug Regimen Review Center Copyright © 2019 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved Contents Executive Summary ......................................................................................................................... 3 Introduction .................................................................................................................................... 8 Table 1. Key Characteristics of Multiple Sclerosis Agents ...................................................... 9 Table 2. Detailed Characteristics of Multiple Sclerosis Agents ............................................. 10 Methods ........................................................................................................................................ 13 Disease Overview .......................................................................................................................... 14 Table 3. The 2017 revision of the 2010 McDonald Criteria for Diagnosis of Multiple Sclerosis................................................................................................................................. 15 Guidelines Recommendations ...................................................................................................... 17 Table 4. Treatment Guideline Recommendations for Multiple Sclerosis in Adults ............. 18 Pharmacology & Special Populations ........................................................................................... 20 Table 5. Mechanism of Action of Multiple Sclerosis Agents ................................................ 21 Table 6. Pharmacokinetic Parameters .................................................................................. 24 Table 7. Special Population Considerations .......................................................................... 25 Direct Comparative Evidence ........................................................................................................ 28 Figure 1. PRISMA Flow Chart for Publication Screening ....................................................... 28 Figure 2. Systematic Reviews Included to Describe the Comparative Efficacy Among Disease-Modifying Agents .................................................................................................... 29 Safety ............................................................................................................................................ 36 Table 8. Warnings and Precautions for Disease-Modifying Agents ..................................... 39 Table 9. Common Adverse Reactions and Monitoring Requirements ................................. 42 Summary ....................................................................................................................................... 44 References .................................................................................................................................... 45 Appendix A – Literature Search Strategies ................................................................................... 49 Appendix B – Included and Excluded References ......................................................................... 55 Appendix C – Evidence from Systematic Reviews of Multiple Sclerosis Agents .......................... 59 Appendix D. Randomized Controlled Trials Included in the Selected Systematic Reviews for Multiple Sclerosis .......................................................................................................................... 65 2 Executive Summary Introduction: Multiple sclerosis (MS) is an inflammatory, autoimmune disease of the central nervous system (CNS) characterized by demyelination and axonal damage. MS is classified into 3 main phenotypes including relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS), with RRMS being the most common. A clinically isolated syndrome (CIS) is the first neurological episode in patients not known to have MS. Disease-modifying therapies (DMTs) aim to reduce disease activity and progression of disability in patients with MS. Interferon (IFN) therapy and glatiramer acetate were the standard of care for treating relapsing forms of MS in the United States for more than 20 years. During the last decade, an increasing number of injectable and oral DMTs has been approved providing multiple treatment options for adults with MS. Currently, 14 DMTs and 1 non-DMT are available for the treatment of MS including oral DMTs (cladribine, dimethyl fumarate, diroximel fumarate, fingolimod, siponimod, and teriflunomide), subcutaneous (SQ) and intramuscular (IM) DMTs (glatiramer acetate, interferon beta-1a, interferon beta-1b, and pegylated interferon beta-1a), intravenous (IV) DMTs (alemtuzumab, mitoxantrone, natalizumab, and ocrelizumab), and the oral non- DMT, dalfampridine. Each DMT is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsing forms of MS including RRMS and active SPMS. In addition, each DMT except alemtuzumab, cladribine, and mitoxantrone is approved for patients with CIS. Ocrelizumab is the only agent approved for PPMS in adults. Fingolimod is the only agent approved for use in the pediatric population (10 years of age or older) with relapsing forms of MS. Due to safety concerns, labeling information for cladribine and alemtuzumab recommends their use only in patients who have had an inadequate response or are intolerant to other drugs indicated for the treatment of MS. The single, non-DMT, dalfampridine, is an oral medication approved for walking improvement in patients with MS. Interferons and the humanized monoclonal antibodies alemtuzumab, natalizumab, and ocrelizumab are biologic products produced by recombinant DNA techniques. Cladribine, dalfampridine, dimethyl fumarate, diroximel fumarate, fingolimod, glatiramer acetate, siponimod, teriflunomide, and mitoxantrone are synthetic drugs. For maintenance dosing, the oral DMTs may be administered once daily (fingolimod, siponimod, teriflunomide) or twice daily (dimethyl fumarate and diroximel fumarate). Cladribine administration includes 2 treatment courses 43 weeks apart. Regarding self-injectable DMTs, glatiramer acetate can be administered daily or 3 times weekly. The interferons are administered once weekly to every other day, with the exception of peg-interferon, administered once every 14 days. The intravenous DMTs are administered every 4 weeks (natalizumab), 3 months (mitoxantrone), or 6 months (ocrelizumab). Alemtuzumab is administered in treatment courses (3 to 5 days long), separated by 12 months apart. The recommended maintenance dosing frequency is twice daily for the non-DMT agent, dalfampridine. The 2018 American Academy of Neurology (AAN) guideline for the treatment of MS recommends offering treatment with DMT to patients with 1 demyelinating event and at least 2 brain lesions consistent with MS, and to patients with relapsing forms of MS who experienced recent relapses or magnetic resonance imaging (MRI) lesion activity. For people with CIS, clinicians may recommend close monitoring rather than starting DMT. Guideline authors provide a moderate recommendation for the use of alemtuzumab, fingolimod, or natalizumab in patients with highly active MS (though no standard definition is currently available for highly active MS). The risk-benefit balance associated with each treatment approach should be evaluated on an individualized basis. Treatment initiation with 3 natalizumab requires consideration of the John Cunningham virus (JCV) antibody status and the potential risk for progressive multifocal leukoencephalopathy (PML). A moderate recommendation is provided for use of ocrelizumab in ambulatory patients with primary progressive multiple sclerosis (PPMS). Mitoxantrone therapy should only be offered to MS patients when the benefits greatly outweigh the risks. DMTs are not recommended for use during pregnancy unless benefits of treatment outweigh potential risks. The 2 recently approved DMTs (diroximel fumarate and siponimod) are not included in the AAN guideline. The aim of this report is to provide evidence from systematic reviews (SRs) and randomized controlled trials (RCTs) of head-to-head efficacy and safety comparisons among the MS agents, at their FDA- approved dosages. Comparative Efficacy Evidence: Following a systematic literature search in Ovid-Medline and Embase for direct head-to-head
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]