DOCSLIB.ORG

Gudesblatt M,1 Wray S,2 Miller C,3 Hanna J,4 Lopez-Bresnahan M,5

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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. completing the 5-week treatment period and those who were newly enrolled to the DRF clinical trial program. Prior DMT, n (%) 452 (65) 0 361 (100) b All patients completed a 2-week safety follow-up; in addition, patients who discontinued or completed treatment with a last measured absolute lymphocyte b count of < 0.8 × 109/L were required to complete lymphocyte follow-up visits for up to 6 additional months. IFN 274 (39) 0 274 (76) GAb 178 (26) 0 178 (49) Introduction Results Mean (SD) time since diagnosis, y 7.6 (7.3) 0.4 (0.5) 9.8 (7.4) • Diroximel fumarate (DRF; ALKS 8700, BIIB098) is a novel oral • As of 30 March 2018, 82 newly diagnosed and 361 prior IFN/GA Figure 2. Patients Treated With DRF in EVOLVE-MS-1 Experienced Reduction From Baseline in ARR Mean (SD) no. of relapses in fumarate in development for patients with relapsing forms of patients were enrolled in EVOLVE-MS-1. 0.8 (0.8) 1.1 (0.7) 0.6 (0.8) previous year multiple sclerosis (MS). • Median (range) DRF exposure was 15.0 (0.4–24.2) months in newly (A) Rate ratio (95% CI) Mean (SD) EDSS score 2.7 (1.5) 2.1 (1.2) 2.86 (1.6) • DRF undergoes rapid, presystemic conversion to monomethyl diagnosed and 14.9 (0.0–24.3) months in prior IFN/GA patients. 0.17 (0.09–0.30) 83.3% reduction + fumarate (MMF), the same pharmacologically active metabolite • Newly diagnosed patients were on average 37 years of age, with Mean (SD) no. of Gd lesions 1.2 (4.0) 2.1 (5.8) 1.0 (3.0) 1 p < 0.0001 as the approved drug, delayed-release dimethyl fumarate (DMF). + 2.1 Gd lesions and 0.4 years since diagnosis; prior IFN/GA patients Rate ratio (95% CI) Patients with Gd+ lesions, n (%) 208 (30) 37 (45) 82 (23) • DRF is differentiated from DMF based on its distinct chemical were on average 44 years of age, with 1.0 Gd+ lesion and 9.8 years 1.5 0.21 (0.16–0.26) Rate ratio (95% CI) DMT = disease-modifying therapy; EDSS = Expanded Disability Status Scale; GA = glatiramer acetate; Gd+ = gadolinium-enhancing; IFN = interferon structure, but is expected to have an efficacy and safety profile since diagnosis (Table). 79.5% reduction 1.11 0.28 (0.20–0.39) aPrior DMT use was permitted with restrictions: patients who were newly enrolled in the diroximel fumarate clinical trial program were not eligible to participate in EVOLVE-MS-1 if they received teriflunomide within 2 years of Visit 2, natalizumab within 2 months of Visit 2, fingolimod within 90 days of Visit 2, and daclizumab within 6 months of Visit 2. similar to DMF when given at the investigated dose because • Overall, 17.1% of newly diagnosed and 19.4% of prior IFN/GA p < 0.0001 (0.98–1.26) 71.9% reduction bSome patients may have received both IFN and GA treatment prior to therapy. both compounds produce bioequivalent levels of systemic MMF patients discontinued DRF treatment. p < 0.0001 upon oral administration. Newly Diagnosed Patients • EVOLVE-MS-1 (NCT02634307) is an ongoing, global, open-label, + a • Adjusted ARR (95% CI) was 0.19 (0.10–0.33) at Week 48, Figure 3. Patients Treated With DRF in EVOLVE-MS-1 Had Reduction From Baseline to Week 48 in Number of Gd Lesions single-arm, Phase 3 study assessing long-term safety, tolerability, 1.0 0.78 and treatment effect of DRF 462 mg twice daily over 96 weeks representing an 83.3% risk reduction compared with the 12 months (0.72–0.84) 0.63 (A) (B) before study start (1.11 [0.98–1.26]; rate ratio [95% CI], 0.17 0 lesions in adults with relapsing-remitting MS (RRMS). (0.55–0.72) 96% lower [0.09–0.30]; p < 0.0001; n = 82; Figure 2A). + 1–4 lesions • Post hoc subgroup analyses were performed to evaluate DRF Gd lesion count • Estimated proportion of patients with a relapse at Week 48 was 5–8 lesions efficacy in 2 MS patient populations: those who were newly p = 0.0051 14% (Figure 2B). ≥ 9 lesions diagnosed with MS and naive to disease-modifying therapies 0.5 0.19 • Mean (SD) EDSS and T25FW scores remained stable over the 2.2 (0.7) (DMTs), and those with greater time since diagnosis and prior Adjusted ARR (95% CI) 3 100 first year of treatment: (0.10–0.33) 0.18 interferon (IFN) beta or glatiramer acetate (GA) use. 0.16 90 89 89 64% lower % (0.13–0.25) – EDSS: baseline, 2.10 (1.15), n = 81; Week 48, 2.25 (1.10), n = 70 + b (0.13–0.20) 77% lower Gd lesion count – T25FW: baseline, 5.78 (2.11), n = 81; Week 48, 6.06 (3.79), n = 70. Gd+ lesion count p < 0.0001 80 75 p < 0.0001 67 Objective • By Week 48, 71 (87%) patients were relapse free, compared with 2 • To explore efficacy outcomes in DRF-treated patients with RRMS 12 (15%) patients in the 12 months before study start. 0.0 60 56 Lesion Count 1.3 (0.2) from the ongoing EVOLVE-MS-1 study who were newly diagnosed + + Baseline Baseline Week 48 Baseline Week 48 1.1 (0.2) Lesion Count, • Mean (SE) Gd lesion count was 2.2 (0.7) at baseline and 0.1 (0.1) Week 48 + with MS or previously treated with IFN or GA. at Week 48 (96% reduction; p = 0.0051; Figure 3A). 40 Overall Populationa Newly Diagnoseda Prior IFN/GAa 33 – A greater percentage of patients had no Gd+ lesions at Week 48 1 (n = 696) (n = 82) (n = 361) 25 compared with baseline (Figure 3B). Methods 0.4 (0.1) 20 18 (B) Mean (SE) Gd 0.3 (0.1) 11 • Patients enrolled in EVOLVE-MS-1 were 18–65 years of age, had a • Mean (SE) numbers of new/newly enlarging T2 hyperintense and 0.1 (0.1) 9 9 Patients by Gd 6 6 5 4 3 2 new T1 hypointense lesions from baseline to Week 48 were 0.3 3 0 1 00 0 1 confirmed RRMS diagnosis, and were neurologically stable with 0 0 no evidence of relapse in the 30 days before screening. 3.0 (0.7) and 2.8 (0.7), respectively (Figure 3C, D). Baseline Week Baseline Week Baseline Week BaselineWeek 48 Baseline Week 48 Baseline Week 48 – Patients in the newly diagnosed group were diagnosed with Prior IFN/GA Patients 48 48 48 RRMS within 1 year of study entry and were naive to DMTs. Overall Population Newly Diagnosed Prior IFN/GA • Adjusted ARR (95% CI) was 0.18 (0.13–0.25) at Week 48, Overall Population Newly Diagnosed Prior IFN/GA (n = 503) (n = 70) (n = 242) – Patients in the prior IFN/GA group had prior IFN or GA use representing a 71.9% reduction from the 12 months before study (n = 503) (n = 70) (n = 242) at any time since diagnosis. start (0.63 [0.55–0.72]; rate ratio [95% CI] 0.28 [0.20–0.39]; 0.2 • Patients received DRF 462 mg twice daily over the 96-week p < 0.0001; n = 361; Figure 2). open-label treatment period; patients newly enrolled in the DRF • Estimated proportion of patients with a relapse at Week 48 clinical trial program initiated treatment with a 1-week titration was 13.4%. (C) (D) period (Figure 1). • By Week 48, 321 (89%) patients were relapse free, compared with 4 3.0 (0.7) 4 • Efficacy endpoints were exploratory; the following endpoints 185 (51%) patients in the 12 months before study start.
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]
  • Ponvory (Ponesimod) Annual Review Date: 05/20/2021
    Policy: Ponvory (ponesimod) Annual Review Date: 05/20/2021 Last Revised Date: 05/20/2021 OVERVIEW Ponvory, a sphingosine 1-phosphate receptor modulator, is indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease in adults. POLICY STATEMENT This policy involves the use of Ponvory. Prior authorization is recommended for pharmacy benefit coverage of Ponvory. Approval is recommended for those who meet the conditions of coverage in the Criteria and Initial/Extended Approval for the diagnosis provided. Conditions Not Recommended for Approval are listed following the recommended authorization criteria. Requests for uses not listed in this policy will be reviewed for evidence of efficacy and for medical necessity on a case-by-case basis. Because of the specialized skills required for evaluation and diagnosis of patients treated with Ponvory as well as the monitoring required for adverse events and long-term efficacy, initial approval requires Ponvory be prescribed by or in consultation with a physician who specializes in the condition being treated. All approvals for initial therapy are provided for the initial approval duration noted below; if reauthorization is allowed, a response to therapy is required for continuation of therapy unless otherwise noted below. RECOMMENDED AUTHORIZATION CRITERIA Coverage of Ponvory is recommended in those who meet the following criteria: 1. Multiple Sclerosis Criteria. Patient must meet the following criteria A) Patient has a relapsing form of multiple sclerosis; AND Note: Examples of relapsing forms of multiple sclerosis include clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease.
    [Show full text]