Insights for Payers. RMS Treatment Considerations and Real-World Evidence Based on a Milliman Actuarial Analysis. RMS=relapsing multiple sclerosis.

Transcription

1 Insights for Payers RMS Treatment Considerations and Real-World Evidence Based on a Milliman Actuarial Analysis RMS=relapsing multiple sclerosis Biogen. All rights reserved. 10/16 FCH-US-1971

2 Agenda Provide an overview of the multiple sclerosis (MS) disease course Describe MS characteristics and diagnosis Review treatment considerations for RMS Explore insights from a 2016 Milliman analysis of commercial MS claims data 2

3 A Few Key Points to Keep in Mind for Today s Presentation This presentation is intended to provide information on the MS landscape, treatment considerations, emerging concepts in the management of RMS, and pharmacoeconomic insights The intent of this presentation is not to provide medical or other advice; all treatment decisions should be up to the discretion of the healthcare provider (HCP) and the patient as each patient s situation may vary This presentation will be completely unbranded and will refrain from mention of specific Biogen relapsing MS therapies This program is sponsored by Biogen, and I am being compensated by Biogen for my time to deliver this presentation 3

4 OVERVIEW OF MS

5 MS Is Thought to Affect 450,000 to More Than 570,000 People in the United States 1,2 Most people with MS are diagnosed between 20 and 50 years of age 3 Approximately 2 to 3 times as many women as men develop RMS, a gender difference that has been increasing over the past 50 years 1,3 Low prevalence rate 1,2 People with MS ~0.15% of the general population ,000 THE RMS PATIENT IS TYPICALLY DIAGNOSED BEFORE THE AGE of 50 AND IS MORE LIKELY TO BE A WOMAN 1,3 1. Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. stories/dmtfullpaper_2015update_final.pdf. Published July Updated March Accessed August 15, Campbell JD et al. Mult Scler Relat Disord. 2014;3(2): National Multiple Sclerosis Society website. Accessed August 15,

6 Neuropathology of MS: Pathophysiological Events Begin Early in the Disease Course 1-3 Example of the Natural History of RMS Over Time 1,4,a Relapses and Impairment Clinical threshold Relapsing-remitting Inflammatory MRI Lesions Inflammation and axonal loss (invisible) a Not representative of all patient populations. Time Adapted from Compston A; Trapp BD. Inflammation Inflammation Inflammation Inflammation Axonal Loss CNS Atrophy 1. Trapp BD et al. Neuroscientist. 1999;5: Kuhlmann T et al. Brain. 2002;125: Paolillo A et al. J Neurol. 2004;251: Compston A et al. Lancet. 2008;372(9648):

7 MS Is a Complex Disease With Multiple Interrelated Pathways 1,2 CNS damage is immune-mediated, with T cells acting as the orchestrators in disease activity 1,2 B cells, macrophages, dendritic cells, and natural killer (NK) cells also play a role in the disease pathogenesis 1,3 Migration of immune cells across the blood-brain barrier (BBB) is a crucial step in MS pathogenesis 4 BLOOD NK cell Th1 Th17 Macrophage B cell Th2 Treg BBB CNS Microglial cells Astrocytes Neurons 1. Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. images/stories/dmtfullpaper_2015update_final.pdf. Published July Updated March Accessed August 15, Weiner HL. Arch Neurol. 2004;61(10): Thewissen K et al. Mult Scler J. 2014;20(5): Larochelle C et al. FEBS Letters. 2011;585:

8 MS CHARACTERISTICS AND DIAGNOSIS

9 Patients With MS May Exhibit a Variety of Symptoms 1,2 Physical Symptoms 1-4 Non-physical Symptoms Visual disturbances, eye pain Headache Heat sensitivity Vertigo Lhermitte s phenomenon Cognitive impairment 1 Depression and mood/emotional changes 2 Pseudobulbar affect 5 Weakness Bladder and bowel dysfunction Spasticity Pain Poor balance, incoordination, gait impairment Numbness, tingling 1. Compston A et al. Lancet. 2008;372: Calabresi P. Am Fam Physician. 2004;70: Gelfand JM. Handb Clin Neurol. 2014;122: Olek MJ. Current Clinical Neurology: Multiple Sclerosis. Totowa, NJ: Humana Press Inc; 2005: Word SS et al. Adv Ther. 2011;28(7):

10 Neurological Impairments Are Highly Prevalent Among Patients With MS PATIENT-REPORTED SYMPTOMS OF NEUROLOGIC IMPARIMENT a Fatigue 80% Diffulty Remembering Pain 52% 52% Difficulty Concentrating Depression 39% 44% Mood Swings Irritability 29% 27% Many neurologic impairments have been linked to higher healthcare costs and/or lost productivity (eg, absenteeism, presenteeism) 2, Percentage of RRMS Patients With Selected Symptoms (N=447) a The results were from combined survey data from 2011 (n=75,000) and 2012 (n=71,157). Only participants with RRMS (n=447) were included in the analysis. 1. Williams AE et al. Mult Scler Int. 2014;2014: Carroll CA et al. BMC Health Serv Res. 2014;14: Glanz BI et al. Value Health. 2012;15(8):

11 Characteristics of the Disease Course Include Clinical and Imaging Features 1 Clinical Imaging Relapses 1 Disability progression 1 CNS lesions detected by magnetic resonance imaging (MRI) 1,2 1. Kamm C et al. Eur Neurol. 2014;72: Image adapted from Filippi M et al. Radiology. 2011;259:

12 Relapses and Disability Progression Are Clinical Characteristics of the Disease Course in MS 1 Relapses Disability progression Newly appearing neurological symptoms that last >24 hours 1 Clinical presentations can include optic neuritis, sensory deficits, or cerebellar dysfunction 1 Patients may recover fully or have residual deficits 1 Disability Time Relapse Deterioration in neurological function over a defined period of time 1,2 Assessed by exams that measure overall neurological function, including both motor and cognitive domains 3 Disability Disability Time Time 1. Kamm C et al. Eur Neurol. 2014;72: Lublin FD et al. Neurology. 2014;83: Polman CH et al. Neurology. 2010;74(suppl 3):S8-S15. 12

13 Disability Progression Based on the Extended Disability Status Scale (EDSS)1,2 DISABILITY PROGRESSION BASED ON THE EDSS 1,2 a No, minimal, and moderate disability refer to disability in 1 functional system, not necessarily overall. EVEN A SMALL INCREASE IN EDSS CAN REFLECT A SIGNIFICANT CHANGE IN A PATIENT S FUNCTIONALITY AND DAILY ACTIVITIES Renoux C. Neurol Clin. 2011;29: Kurtzke JF. Neurology. 1983;33(11):

14 MRI Evaluation Is a Valuable Diagnostic Tool for MS MRI can be useful in the diagnostic evaluation for MS because 95% of MS patients present lesions on MRI at the time of diagnosis 1 Inflammation, tissue damage, and lesion activity can be measured with the following MRI parameters 1 : Gadolinium-enhancing lesions indicate sites of active inflammation and breakdown of the BBB 1 T1 hypointense lesions ( black holes ) can reflect significant, long-term 95 % tissue damage 2 T2 hyperintense lesions can indicate the cumulative burden of lesion activity 1 THE REVISED CONSORTIUM OF MULTIPLE SCLEROSIS CENTERS GUIDELINES 95 % RECOMMEND CONSIDERING MRI EVALUATION TO ASSESS SUBCLINICAL DISEASE ACTIVITY 3,4 Every 12 to 24 months for low-risk patients Every 6 to 12 months for high-risk patients 1. National Multiple Sclerosis Society website. Accessed August 15, Thaler C et al. PLoS ONE. 2015;10(12): Consortium of Multiple Sclerosis Centers. 9C5F19B B0-A54B-623A1ECEE07B /mriprotocol2009.pdf. Accessed August 15, Consortium of Multiple Sclerosis Centers. sites/ resource/collection/9c5f19b b0-a54b-623a1ecee07b/2015mri_primer.pdf. Accessed August 15,

15 RMS TREATMENT CONSIDERATIONS

16 Defining DMT A disease-modifying therapy, or DMT, is a drug that is oral, injectable, or infused that has been approved by the United States Food and Drug Administration (FDA) 1,2 DMTs are not a cure for relapsing forms of MS, but most have been shown to affect 1 FDA-approved DMTs for the treatment of RMS 2 Reduction in the frequency of clinical attacks or exacerbations Injectable medications Reduction in brain lesions as detected by MRI Oral medications Slowing of physical disability progression Infused medications 1. National Multiple Sclerosis Society. The MS Disease-Modifying Medications. Brochures/Brochure-The-MS-Disease-Modifying-Medications.pdf. Accessed August 15, Medications National Multiple Sclerosis Society website. Accessed August 15,

17 DMT Has Been Shown to Be Associated With Reduced Healthcare Resource Utilization RESOURCE UTILIZATION AMONG PATIENTS WITH MS BY DMT USE IN 2012 Admissions per 100 patients Hospital Admissions 36% change Average Length of Stay (Days) Hospital Length of Stay 16% change ER Visits per 100 Patients ER Visits 39% change Patients with MS treated with DMT (n=10,876) Patients with MS not treated with DMT (n=25,431) FACILITY COSTS HAVE BEEN SHOWN TO BE THE PRIMARY DRIVER OF COST FOR PATIENTS WITH MS WHO ARE NOT TREATED WITH DMT. Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. Livingston T et al. Analysis of health care resource use and cost in DMT-treated versus non-dmt-treated patients with multiple sclerosis in the United States. Poster presented at: Academy of Managed Care Pharmacy 26th Annual Meeting & Expo. April 1-4, 2014; Tampa, FL. 17

18 Key Treatment Considerations Support Initiating DMT Promptly After Diagnosis MS treatment guidelines in the United States do not endorse a specific treatment algorithm due to the heterogeneity of the patient population The goal of disease-modifying treatment is to reduce the early clinical and sub-clinical disease activity that is thought to contribute to long-term disability. Multiple Sclerosis Coalition The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence Page 11 LONG-TERM DISABILITY IN MS MAY BE IMPACTED BY EARLY DISEASE ACTIVITY. DMT=disease-modifying therapy. Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. stories/dmtfullpaper_2015update_final.pdf. Published July Updated March Accessed August 15,

19 Treatment May Reduce the Risk of Long-Term Disability Progression a IN ONE OBSERVATIONAL STUDY INVOLVING 3060 MS PATIENTS, THE RISK OF LONG-TERM DISABILITY PROGRESSION WAS REDUCED FOR PATIENTS TREATED WITH IMMUNOMODULATORY OR IMMUNOSUPPRESSIVE THERAPIES COMPARED WITH UNTREATED PATIENTS 90% Reduction in risk of progression to EDSS 3.0 in 1735 treated patients compared with 781 untreated patients with a median follow-up of 12 years 62% Reduction in risk of progression to EDSS 6.0 in 1904 treated patients compared with 539 untreated patients with a median follow-up of 12 years a No DMTs, including those from Biogen, have been FDA approved to demonstrate these benefits. Cocco E et al. Mult Scler. 2015;21:

20 Reducing Relapse Frequency May Be an Important Factor for Delaying Disease Progression 1-3 Higher relapse frequency early in the course of disease may be associated with more rapid disease progression 1-3 Even early relapses with full recovery may have permanent neurologic consequences 2 A shorter time interval between the onset of MS and a second neurological episode has been associated with more rapid disease progression 2 Approximately 42% of relapses result in some form of disability or loss of function 4 1. Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. stories/dmtfullpaper_2015update_final.pdf. Published July Updated March Accessed August 15, Confavreux C et al. Brain. 2003;126: Hutchinson M et al. Pract Neurol. 2009;9: Lublin FD. Neurology. 2003;61(11):

21 DMT Treatment May Reduce Risk of Progression to Secondary Progressive MS a SECONDARY PROGRESSION-FREE SURVIVAL FOR LOW-RISK PATIENTS (FIRST BREMS QUARTILE) SECONDARY PROGRESSION-FREE SURVIVAL FOR HIGH-RISK PATIENTS (FOURTH BREMS QUARTILE) Progression-Free Survival Probability Treated with DMTs Untreated P< Progression-Free Survival Probability Treated with DMTs Untreated P< Time (Years) Time (Years) n= n= n= n= Adapted from Bergamaschi R et al. Mult Scler. 2012;0:1-9. Study design: A total of 1178 patient with RMS at onset and for at least 10 years were divided into 2 groups (treated with DMTs and untreated). The study used a Bayesian graphical model to calculate a value related to the risk to reach secondary progression. a No DMTs, including those from Biogen, have been FDA approved to demonstrate these benefits. BREMS=Bayesian risk estimate for multiple sclerosis. Bergamaschi R et al. Mult Scler. doi: /

22 A Correlation Has Been Shown Between Disability Level and Total Cost in MS 1 TOTAL COST BY DISABILITY LEVEL 70,000 $64,492 60,000 50,000 $49,800 Cost ($) 40,000 30,000 20,000 $32,297 10,000 0 (EDSS <4.0) (EDSS ) (EDSS 6.0) a Based on a 2006 cross-sectional mail survey study in the United States. A sample of 4000 patients treated with injectable DMT was selected from the North American Research Committee on Multiple Sclerosis. A total of 1909 patients with MS completed the survey. Please note that the limitations of these 2006 data are inclusive of interferon beta-1a, interferon beta-1b, and glatiramer acetate injection, and do not incorporate any additional DMTs. IN ANOTHER STUDY, THE COST OF MANAGING A SEVERELY DISABLED PATIENT (EDSS ) WAS APPROXIMATELY 2 TO 3 TIMES THAT FOR A PATIENT WITH MILDER DISABILITY (EDSS ). 2 Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. 1. Kobelt G et al. Neurology. 2006;66(11): Karampampa K et al. Mult Scler. 2012;18(suppl 2):

23 DMTs Are Not Interchangeable 1 Currently approved DMTs offer diverse characteristics such as mechanisms of action, benefit-risk profiles, routes of administration, safety, and efficacy 1,2 The limited number of head-to-head trials may result in uncertainty when selecting an RMS therapy 1 The therapeutic landscape in MS may continue to evolve, with several agents in development 3 1. Bourdette DN et al. Neurol Clin Pract. 2016;6(2): Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. Published July Updated March Accessed August 15, Ali R et al. Drugs. 2013;73:

24 DMT Selection Is Highly Complex and Patient-Specific 1 EFFICACY The efficacy of DMTs may vary from one individual to another and for any given individual at different points in time 1 TREATMENT Treatment decisions take into account patient attitudes about their disease, how the disease affects their life (eg, considerations with pregnancy), and risk-benefit profile of the therapy 2,3 CONSENSUS GUIDELINES BY THE MULTIPLE SCLEROSIS COALITION RECOMMEND THAT PATIENTS AND HEALTHCARE PROFESSIONALS SHOULD HAVE CONTINUOUS ACCESS TO A FULL RANGE OF DMT OPTIONS Bourdette DN et al. Neurol Clin Pract. 2016;6(2): National Multiple Sclerosis Society website. Accessed August 15, Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. Published July Updated March Accessed August 15,

25 The Complexity of MS Requires Treatment Flexibility Intolerable side effects Active disease is one of the most common reasons for transitioning to another DMT 1 Other clinical considerations for transitioning DMTs may include 1 Neutralizing antibodies Risk of life-threatening infection THE MS COALITION RECOMMENDS THAT FLEXIBLE TREATMENT OPTIONS NEED TO BE ACCESSIBLE DUE TO THE VARIABILITY OF DISEASE COURSE AND PATIENT HETEROGENEITY Gallo P, Van Wijmeersch B; ParadigMS Group. Eur J Neurol. 2015;22(suppl 2): Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. Published July Updated March Accessed August 15,

26 PHARMACOECONOMIC INSIGHTS: CLAIMS-BASED OUTCOMES IN MS

27 Real-World Evidence: Important Background Information MS SCOPE OF THIS WORK In this study, we examined the healthcare costs and disease markers of patients identified with MS. The context is the changes in disease burden over the course of several years, including the years leading up to diagnosis. The source for the information in these slides comes from the white paper titled Multiple Sclerosis: New Perspectives on the Patient Journey. DATA SOURCES For our commercial analysis, we used the Truven Health Analytics MarketScan Commercial Databases ( ).These databases include health insurance claims across the continuum of care as well as enrollment data for tens of millions of insured lives from self-funded large employers and health plans across the United States. Wolters Kluwer s Medi-Span database was used to identify AWP unit prices for all DMT drugs. Medi-Span is a comprehensive drug data source that contains brand and generic drug names, national drug code (NDC), generic product identifier (GPI), manufacturer information, and various price metrics for close to 200,000 drug products. 27

28 Real-World Evidence: Important Background Information (cont d) CAVEATS AND SPONSORSHIP This material shows averages across patients. Individual patients may have higher or lower costs, disease markers, and DMT use than the averages shown. In charts that show care by category, not all patients will receive all categories shown. This work was commissioned by Biogen. The paper reflects the research of the authors and was developed with the intent to provide insight to financial and medical decision-makers within payer organizations. It should not be considered an endorsement of any policy or product by Milliman, Inc. Medical therapy, especially biotechnology, is a rapidly changing field, and readers should note that this paper may not reflect current therapeutic considerations. The patient journey is individualized and may differ from patient to patient. The figures presented here are, unless otherwise noted, national averages developed from historical databases. Because of the variability in healthcare and health benefits, these figures may not be appropriate for particular organizations or particular purposes. As with any economic or actuarial analysis, it is not possible to capture all factors that may have significant impact on healthcare utilization and cost. Interpretations of these data may vary. Further, no algorithm for identifying MS patients and relapses will be perfect. Different identification algorithms could produce different results. It is important to note that individual patient characteristics and situations may also vary. MS 28

29 Claims Data Were Analyzed by Milliman to Provide New Insights Into Patient and Treatment Dynamics Two analyses were conducted using data from Truven Health Analytics MarketScan Commercial Databases Includes data for tens of millions of insured lives from self-funded large employers and health plans across the United States Snapshot analysis for the year 2013 (~48,700 patients with MS) Prevalence Incidence DMT treatment rate Healthcare costs Longitudinal analysis for the years (~15,900 newly diagnosed patients with MS, followed for up to 10 years after diagnosis) Disability and impairment markers DMT treatment initiation Non-DMT costs DMT impact (regression model) DMT use patterns Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. Pyenson B et al. Multiple Sclerosis: New Perspectives on the Patient Journey. Milliman, Inc. NY. April

30 Most Patients With MS Have 1 or More Indicators of the Disease at Time of Diagnosis CUMULATIVE DISTRIBUTION OF PATIENTS WITH MS BY THE NUMBER OF DISABILITY/IMPAIRMENT INDICATORS DURING THE COURSE OF THE DISEASE Indicators Percentage of Patients With MS 100% 80% 60% 40% 20% 5% 10% 18% 33% 32% 2% 10% 13% 17% 21% 24% 15% 20% 23% 15% 16% 17% 18% 18% 19% 20% 20% 19% 22% 19% 17% 15% 11% 8% 5% 0% Year(s) From Initial MS Diagnosis Study design: Milliman analyzed a large administrative database comprising commercial health insurance claims data in a snapshot analysis for 2013 and a longitudinal analysis for 2003 to The analysis included MS patients with diverse resource utilization as exhibited by considerable variations of allowed costs. The longitudinal analysis examined disability accumulation, treatment patterns of DMT, and related healthcare costs in newly diagnosed patients over the course of 10 years. Pyenson B et al. Multiple Sclerosis: New Perspectives on the Patient Journey. Milliman, Inc. NY. April

31 Non-DMT Costs Appeared to Increase Above the Prior Years Level in the Two Years Prior to Diagnosis ALLOWED PPPM COSTS ASSOCIATED WITH NON-DMT SERVICES DURING THE COURSE OF THE DISEASE (including 95% CIs and trended to 2015) $2,000 $1614 Average Allowed PPPM for Non-DMT Cost $1,600 $1,200 $800 $400 $591 $612 $655 $732 $1128 $1146 $1162 $1145 $1180 $1226 $1252 $1157 $0 Year -5 Year -4 Year -3 Year -2 Year -1 Year 0 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Years From Initial MS Diagnosis Study design: Milliman analyzed a large administrative database comprising commercial health insurance claims data in a snapshot analysis for 2013 and a longitudinal analysis for 2003 to The analysis included MS patients with diverse resource utilization as exhibited by considerable variations of allowed costs. The longitudinal analysis examined disability accumulation, treatment patterns of DMT, and related healthcare costs in newly diagnosed patients over the course of 10 years. NON-DMT COSTS APPEARED TO PEAK IN THE YEAR FOLLOWING MS DIAGNOSIS AND REDUCED SOMEWHAT THEREAFTER. Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. PPPM=per patient per month. Pyenson B et al. Multiple Sclerosis: New Perspectives on the Patient Journey. Milliman, Inc. NY. April

32 Non-DMT Items Comprised Approximately 37% of the Average Allowed Cost for Patients With MS ALLOWED PPPM CLAIM COSTS BY SERVICE CATEGORY FOR PATIENTS WITH MS IN 2013 $4000 Average Allowed PPPM Cost $3500 $3000 $2500 $2000 $1500 $1000 $500 $0 $2386 $1407 Total Cost Non-DMT Cost $324 $291 $286 $269 $180 $57 Non-DMT Prescription Drugs Inpatient & Skilled Nursing Facility Outpatient Professional & Other Services Radiology & Pathology ER DMT Non-DMT Study design: Milliman analyzed a large administrative database comprising commercial health insurance claims data in a snapshot analysis for 2013 and a longitudinal analysis for 2003 to The analysis included MS patients with diverse resource utilization as exhibited by considerable variations of allowed costs. The longitudinal analysis examined disability accumulation, treatment patterns of DMT, and related healthcare costs in newly diagnosed patients over the course of 10 years. HOSPITALIZATIONS, SKILLED NURSING FACILITY STAYS, AND ER VISITS MADE UP NEARLY ONE-QUARTER OF NON-DMT COSTS. Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. ER=emergency room. Pyenson B et al. Multiple Sclerosis: New Perspectives on the Patient Journey. Milliman, Inc. NY. April

33 The Average Allowed PPPM Claim Cost for Patients With MS Was $3793 ALLOWED PPPM CLAIM COSTS FOR PATIENTS WITH MS IN 2013 TOTAL COST DMT COST NON-DMT COST 95 th Percentile $10,306 = + 95 th Percentile 95 th Percentile $5149 $5157 Mean: $3793 Mean: $2386 ~2-fold increase Mean: $1407 >3-fold increase $95 10 th Percentile $0 10 th Percentile $95 10 th Percentile Study design: Milliman analyzed a large administrative database comprising commercial health insurance claims data in a snapshot analysis for 2013 and a longitudinal analysis for 2003 to The analysis included MS patients with diverse resource utilization as exhibited by considerable variations of allowed costs. The longitudinal analysis examined disability accumulation, treatment patterns of DMT, and related healthcare costs in newly diagnosed patients over the course of 10 years. MS PATIENTS HAD DIVERSE RESOURCE UTILIZATION AS EXHIBITED BY CONSIDERABLE VARIATIONS IN ALLOWED COSTS, PARTICULARLY FOR NON-DMT ITEMS. Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. Pyenson B et al. Multiple Sclerosis: New Perspectives on the Patient Journey. Milliman, Inc. NY. April

34 Untreated Patients With MS Appeared to Have Higher Costs for Non-DMT Items Than DMT-Treated Patients Average Allowed PPPM Non-DMT Cost ALLOWED NON-DMT PPPM CLAIM COSTS BY DMT USE FOR PATIENTS WITH MS IN 2013 (including 95% CIs) $2000 $1750 $1500 $1250 $1000 $750 $500 $250 $0 $1407 $ % difference $1312 All Patients Patients Without DMT Use Patients With DMT Use Study design: Milliman analyzed a large administrative database comprising commercial health insurance claims data in a snapshot analysis for 2013 and a longitudinal analysis for 2003 to The analysis included MS patients with diverse resource utilization as exhibited by considerable variations of allowed costs. The longitudinal analysis examined disability accumulation, treatment patterns of DMT, and related healthcare costs in newly diagnosed patients over the course of 10 years. IN 2013, THE UNADJUSTED AVERAGE MONTHLY NON-DMT COST AMONG PATIENTS WITH DMT USE WAS APPROXIMATELY 18% LOWER THAN AMONG THOSE WITHOUT DMT USE. POTENTIAL CONFOUNDING FACTORS LIKE AGE, GENDER, AND DISEASE DURATION WERE NOT ADJUSTED FOR IN THIS ANALYSIS. Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. Pyenson B et al. Multiple Sclerosis: New Perspectives on the Patient Journey. Milliman, Inc. NY. April

35 Approximately 33% of Newly Diagnosed Patients With MS Had No DMT Claims in the 2 Years After Diagnosis DMT TREATMENT PATTERNS FOLLOWING A 2-YEAR PERIOD FOR PATIENTS NEWLY DIAGNOSED WITH MS IN Newly Diagnosed Patients With MS (%) % 67% Patients Diagnosed in 2012 (n=1300) 31% 69% Patients Diagnosed & Initiated on DMT (n=866) Transitioned to 1 DMTs Used 1 DMT No DMT use DMT use Study design: Milliman analyzed a large administrative database comprising commercial health insurance claims data in a snapshot analysis for 2013 and a longitudinal analysis for 2003 to The analysis included MS patients with diverse resource utilization as exhibited by considerable variations of allowed costs. The longitudinal analysis examined disability accumulation, treatment patterns of DMT, and related healthcare costs in newly diagnosed patients over the course of 10 years. APPROXIMATELY 1 OUT OF 3 PATIENTS TRANSITIONED TO A DIFFERENT DMT WITHIN 2 YEARS AFTER INITIATING TREATMENT. Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. Pyenson B et al. Multiple Sclerosis: New Perspectives on the Patient Journey. Milliman, Inc. NY. April

36 Milliman Analysis Contact your Biogen Account Manager for more information and a copy of Multiple Sclerosis: New Perspectives on the Patient Journey, a report by Milliman that presents findings of a commercial claims analysis of more than 10 years duration. 36

37 SUMMARY

38 Summary Inflammation, axonal loss, and CNS atrophy begin early in the disease, which is one reason guidelines recommend timely DMT treatment to help reduce the progression of physical disability 1-4 Treatment with DMTs may be an option that requires flexibility for prescribers and patients because of the complexity of patient individuality, disease progression, and treatment response 4 Managing patients with higher EDSS ( ) has been shown to cost 2 to 3 times more than managing patients with an EDSS of DMT use has been shown to decrease hospital admissions, length of stay, and ER visits 6 Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. 1.Trapp BD et al. Neuroscientist. 1999;5: Kuhlmann T et al. Brain. 2002;125: Paolillo A et al. J Neurol. 2004;251: Multiple Sclerosis Coalition. The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. DMTfullpaper_2015update_final.pdf. Published July Updated March Accessed August 15, Karampampa K et al. Mult Scler. 2012;18(suppl 2): Livingston T et al. Analysis of health care resource use and cost in DMT-treated versus non-dmt-treated patients with multiple sclerosis in the United States. Poster presented at: Academy of Managed Care Pharmacy 26th Annual Meeting & Expo. April 1-4, 2014; Tampa, FL. 38

39 Summary (cont d) According to an analysis by Milliman 1 Non-DMT costs appeared to increase leading up to diagnosis, which may account for misdiagnosis or exacerbations prior to having an MS diagnosis Within 2 years of initiating treatment, approximately one third of patients transitioned to a different DMT Almost one quarter of non-dmt costs were attributed to acute care, including hospitalizations, skilled nursing facility stays, and ER visits In 2013, the average monthly non-dmt cost among patients with DMT use ($1312) was approximately 18% lower than among those without DMT use ($1593) Approximately one-third of newly diagnosed patients with MS did not use DMT in the first 2 years following diagnosis Intended only for the distribution to members of formulary committees or similar entities pursuant to Section 114 of the FDA Modernization Act. 1. Pyenson B et al. Multiple Sclerosis: New Perspectives on the Patient Journey. Milliman, Inc. NY. April

40 Insights for Payers RMS Treatment Considerations and Real-World Evidence Based on a Milliman Actuarial Analysis RMS=relapsing multiple sclerosis Biogen. All rights reserved. 10/16 FCH-US-1971