Biogen Sweden AB

• Efter upp till 4.8 år av kontinuerlig behandling med Spinraza var 100 procent av de pre-symptomatiskt behandlade patienterna i livet och ingen var beroende av permanent ventilation.
• Patienterna fortsatte att göra och bibehålla sina framsteg avseende motorisk funktion i jämförelse med det naturliga sjukdomsförloppet, med 96 procent som nu kan gå med hjälp av stöd.
• NURTURE studien förlängdes nyligen för att utvärdera Spinrazas långtidseffekt och säkerhet i åldrar upp till 8 år.

Cambridge, Mass. – June 10, 2020 – Biogen Inc. (Nasdaq: BIIB) today announced new results from NURTURE, the longest study of pre-symptomatic patients with spinal muscular atrophy (SMA) that is transformingexpectations of early treatment with nusinersen. In infants genetically diagnosed with SMA, new data demonstrate that early and sustained treatment with nusinersen for up to 4.8 years enabled all patients to survive. These results are being presented at the virtualCure SMA Research & Clinical Care Meeting taking place June 10-12, 2020.

The new data include nearly a year of additional follow-up for NURTURE study participants. As of February 2020, all patients treated (n=25; median age of 3.8 years old) were alive and remained free of permanent ventilation. In the absence of treatment, the majority of children with SMA Type 1 would, on average, not reach their second birthday. Additionally, all children who achieved the motor milestone of being able to walk independently (many within a normal timeframe) have maintained that ability from the first occurrence until the last visit.

NURTURE is an ongoing, Phase 2, open-label study of 25 pre-symptomatic patients with the genetic diagnosis of SMA (most likely to develop SMA Type 1 or 2) who received their first dose of nusinersen before 6 weeks old. The study has been extended by an additional three years, enabling Biogen to evaluate the longer-term efficacy and safety of nusinersen through 8 years of age and further understand the impact of early treatment. More information on the NURTURE study (NCT02386553) is available on clinicaltrials.gov.

Additional results from the updated interim analysis as of February 2020 show:

• All study participants who were previously able to walk with assistance (92 percent) and walk independently (88 percent) maintained that ability over the 11 months since the last data cut.¹
• Over the 11 months of follow-up, one child gained the ability to walk with assistance (increasing to 96 percent of all study participants) and also reached the maximum score on the Children’s Hospital of Pennsylvania Infant Test of Neuromuscular Disorders (CHOP-INTEND) scale, increasing the total number of study participants who achieved the maximum score to 21 of 25 (84 percent).
• Patients with two copies of SMN2 were able to score and advance on the Hammersmith Functional Motor Scale Expanded scale (HFMSE), which is atypical to the natural history of the disease.
• Nusinersen was well-tolerated, with no new safety concerns identified over the extended follow-up period. No children have discontinued the study due to adverse events associated with treatment.

Om nusinersen

Nusinersen är avsett för behandling av spinal muskelatrofi av typ 5q. Biverkningar som observerats är fall av allvarlig infektion, såsom meningit. Det har även förekommit rapporter om kommunicerande hydrocefalus, aseptisk meningit och överkänslighet (t.ex. angioödem, urtikaria och hudutslag). För information om kontraindikationer, varningar och försiktighet, biverkningar, dosering och förpackningar se www.fass.se.

About Biogen

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimer’s disease and dementia, neuromuscular disorders, movement disorders, ophthalmology, immunology, neurocognitive disorders, acute neurology and pain.

We routinely post information that may be important to investors on our website at www.biogen.com. To learn more, please visit www.biogen.com.

Biogen Safe Harbor

This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential benefits, safety and efficacy of nusinersen; the results of certain real-world data; the identification and treatment of SMA; clinical development programs, clinical trials and data readouts and presentations; and the potential benefits and results from early treatment of SMA. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies; failure to obtain regulatory approvals in other jurisdictions; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

References:

1. De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Disord. 2019;29(11):842‐856. doi:10.1016/j.nmd.2019.09.007.
2. Based on Commercial Patients, Early Access Patients, and Clinical Trial Participants as of March 31, 2020.
3. Finkel R, Chiriboga C, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017-3026.
4. Darras B, Markowitz J, Monani U, De Vivo D. Chapter 8 - Spinal Muscular Atrophies. In: Vivo BTD, ed. Neuromuscular Disorders of Infancy, Childhood, and Adolescence (Second Edition). San Diego: Academic Press; 2015:117-145.

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MEDIA CONTACT:

Mats Ekelund

+46 76 182 36 27

mats.ekelund@biogen.com

• Behandling med Spinraza förbättrade eller stabiliserade motoriska funktioner hos olika typer av patienter, inklusive unga vuxna.
• Spinrazas långsiktiga säkerhetsprofil var densamma för ett brett spektrum av åldrar och typer av SMA.
• Nya data bidrar till den betydande mängden evidens som bekräftar den kliniskt meningsfulla och kvarstående nyttan som Spinraza ger hos småbarn, barn och unga vuxna behandlade i upp till sex och ett halvt år.

Cambridge, Mass. – May 18, 2020 – Biogen Inc. (Nasdaq: BIIB) today announced additional data from the SPINRAZA (nusinersen) clinical development program that further demonstrate the sustained efficacy and longer-term safety of SPINRAZA in a broad range of patients with spinal muscular atrophy (SMA). These new data were selected for presentation at the 72nd American Academy of Neurology (AAN) annual meeting and will be available online via the 2020 AAN Science Highlights virtual platform.

“As the first approved treatment for SMA, SPINRAZA offers a significant data set that allows us to assess the safety and durability of repeated doses over time in individuals across age groups and varying disease severity,” said Alfred Sandrock, Jr., M.D., Ph.D., Executive Vice President, Research and Development at Biogen. “New data show that continuous treatment with SPINRAZA for up to six and a half years improved or stabilized motor function and disease activity in a broad spectrum of patients with SMA. These results are in stark contrast to the expected natural history of the disease. Further, in a progressive disease like SMA, stabilization is an important measure of treatment success, allowing patients to retain motor function that may otherwise be lost.”

New Data Reinforce Sustained Efficacy and Longer-Term Safety of SPINRAZA Across Age Groups and SMA Types

The SHINE open-label extension study (NCT02594124) has enrolled 292 patients (infants through teenagers) from five previous SPINRAZA clinical studies, including ENDEAR.New findings from the SHINE study show treatment with SPINRAZA resulted in motor function improvement or disease stabilization in toddlers, children and young adults who were treated continuously, some for up to six and a half years.

Key highlights include:

• Patients with infantile-onset SMA included in the ENDEAR-SHINE study (n=105) and who had earlier initiation of SPINRAZA treatment experienced the greatest benefit, and those with later initiation showed evidence of motor function stabilization or improvement.
• A separate analysis evaluated a cohort of seven young adults (Type 2 or 3) who began treatment with SPINRAZA as teenagers (aged 13 to nearly 16 years old) and have since been treated for up to six and a half years (range of 5.3 to 6.8 years). Most of these patients demonstrated generally stable or improved motor function throughout the follow-up period as assessed by the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module and Upper Limb Module (RULM/ULM) and Six-Minute Walk Test (6MWT).
  • Results also measured the impact on participants’ caregivers via the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND), with the majority reporting stable or decreased impact over the same period. ACEND is an outcomes instrument specifically designed to assess the caregiver impact experienced by caregivers raising children affected by neuromuscular disease, including physical, emotional and financial domains.¹
• The durability of SPINRAZA was also demonstrated in individuals with later-onset SMA (n=126), as HFMSE and RULM scores were stable.
• In all SHINE presentations, the safety profile of SPINRAZA was consistent with previously reported findings.

AAN data presentations highlighted in this release include:

• Nusinersen in Infantile-onset Spinal Muscular Atrophy: Results From Longer-term Treatment From the Open-label SHINE Extension Study
• Longer-term Experience With Nusinersen in Young Adults With Spinal Muscular Atrophy: Results From the CS2/CS12 and SHINE Studies
• Longer-term Treatment With Nusinersen: Results in Later-onset Spinal Muscular Atrophy From the SHINE Study
• Safety Profile of Nusinersen in Presymptomatic and Infantile-Onset Spinal Muscular Atrophy (SMA): Interim Results From the NURTURE and ENDEAR-SHINE Studies

Om Spinraza

Spinraza är avsett för behandling av spinal muskelatrofi av typ 5q. Biverkningar som observerats är fall av allvarlig infektion, såsom meningit. Det har även förekommit rapporter om kommunicerande hydrocefalus, aseptisk meningit och överkänslighet (t.ex. angioödem, urtikaria och hudutslag). För information om kontraindikationer, varningar och försiktighet, biverkningar, dosering och förpackningar se www.fass.se.

About Biogen

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimer’s disease and dementia, neuromuscular disorders, movement disorders, ophthalmology, immunology, neurocognitive disorders, acute neurology and pain.

Biogen Safe Harbor

This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential benefits, safety and efficacy of SPINRAZA; the results of certain real-world data; the identification and treatment of SMA; clinical development programs, clinical trials, and data readouts and presentations; and the potential benefits and results from early treatment of SMA. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies; failure to obtain regulatory approvals in other jurisdictions; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

References:

1. Matsumoto H, Clayton-Krasinski DA, Klinge SA, et al. Development and initial validation of the assessment of caregiver experience with neuromuscular disease. J Pediatr Orthop. 2011;31(3):284-292.
2. Based on Commercial Patients, Early Access Patients, and Clinical Trial Participants as of March 31, 2020.
3. Finkel R, Chiriboga C, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017-3026.
4. Darras B, Markowitz J, Monani U, De Vivo D. Chapter 8 - Spinal Muscular Atrophies. In: Vivo BTD, ed. Neuromuscular Disorders of Infancy, Childhood, and Adolescence (Second Edition). San Diego: Academic Press; 2015:117-145.

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​Nya analyser av en större mängd data visade att aducanumab minskade den kliniska försämringen hos patienter med tidig Alzheimers sjukdom, mätt med de fördefinierade primära och sekundära effektmåtten.

Baserad på diskussioner med den amerikanska läkemedelsmyndigheten FDA, planerar Biogen att ansöka om godkännande under början av 2020.

Företaget hoppas kunna erbjuda aducanumab till patienter som tidigare deltagit i kliniska studier.

De positiva resultaten från den nya analysen beror primärt på högre doser aducanumab i den större mängden data jämfört med tidigare tillgängliga data som ingick i futilitetsanalysen.

Cambridge, Massachusetts och Tokyo, Japan. Biogen och Eisai meddelade den 22 oktober 2019 att, efter samråd med den amerikanska läkemedelsmyndigheten FDA, att Biogen planerar att fullfölja ansökan om godkännande av aducanumab, en behandling mot Alzheimers sjukdom. Fas 3-studien ”EMERGE”, uppfyllde sitt primära effektmått och visar en statistiskt signifikant minskning av den kliniska försämringen i sjukdomen. Biogen anser att resultaten från en undergrupp patienter i fas 3-studien ENGAGE, som fick högre doser av aducanumab stödjer resultaten från EMERGE.

Patienter som fick aducanumab upplevde betydande kognitiva och funktionella fördelar vad gäller minne, orienteringsförmåga och tal. Patienter upplevde även förbättringar i vardagliga aktiviteter så som att sköta sin privatekonomi, att utföra hushållssysslor som till exempel städa, handla och tvätta, samt resa på egen hand utanför hemmet.

Om aducanumab godkänns, kommer det att vara den första behandlingen som minskar den kliniska nedgången av Alzheimers sjukdom, och visar att reducerad ansamling av beta-amyloid resulterar i bättre kliniska resultat.

Beslutet att ansöka om godkännande är baserat på en ny analys, genomförd av Biogen i samråd med FDA, av ett större dataset från de kliniska fas 3-studierna som avbröts i mars 2019 efter en futilitetsanalys. Denna nya analys av en större mängd data, som inkluderar ytterligare data som blev tillgängliga efter den i förväg specificerade futilitetsanalysen, visar att aducanumab är farmakologiskt och kliniskt aktivt. Det kan fastställas genom dosberoende effekter som minskar ansamlingen av hjärnamyloid och minskar den klinisk försämringen som bedömts av det fördefinierade primära effektmåttet CDR-SB (skala för att kliniskt skatta demens). I båda studierna var säkerhets- och tolerabilitetsprofilen för aducanumab överensstämmande med tidigare studier av aducanumab.

Baserat på diskussioner med FDA planerar Biogen att lämna in en BLA-ansökan (Biologics License Application) i början av 2020. Därefter kommer företaget fortsätta dialogen med registreringsmyndigheter i bland annat Europa och Japan. Ansökan kommer att innefatta data från fas 1/1b ”PRIME”-studier, samt den kompletta uppsättningen av data från fas 3-studierna.

Biogens mål är att kunna erbjuda aducanumab för berättigade patienter som tidigare har deltagit i fas 3-studier, den långsiktiga förlängningsstudien för fas 1b PRIME-studien och säkerhetsstudien EVOLVE. Biogen kommer att arbeta skyndsamt mot detta mål tillsammans med berörda myndigheter och prövare.

Studieresultat

Studierna EMERGE (1 638 patienter) och ENGAGE (1 647 patienter) var båda fas 3-, multicenter-, randomiserade, dubbelblinda, placebokontrollerade, parallellgruppstudier utformade för att utvärdera effekt och säkerhet för två doseringsregimer av aducanumab. Studierna avbröts den 21 mars 2019 efter resultaten av en fördefinierad futilitetsanalys som byggde på ett tidigare och mindre mängder data.

Futilitetsanalysen baserades på tillgängliga data till och med den 26 december 2018 från
1 748 patienter som hade möjlighet att slutföra studieperioden på 18 månader. Analysen visade att det inte var sannolikt att någon av studierna skulle uppfylla sina primära effektmått. Futilitetsanalyser är vanliga i stora kliniska studier och använder statistisk modellering för att försöka förutsäga resultatet av studierna baserat på ett antal förutbestämda antaganden och kriterier.

Efter avslutandet av EMERGE och ENGAGE blev ytterligare data från dessa studier tillgängliga vilket resulterade i en större mängd data, som omfattade totalt 3 285 patienter, varav 2 066 hade möjlighet att fullfölja hela behandlingsperioden på 18 månader. En ny omfattande analys av denna större mängd data visade ett annat resultat än det resultat som förutsades av futilitetsanalysen. Mer specifikt visade den nya analysen med den större mängden data att EMERGE var statistiskt signifikant för det förspecificerade primära effektmåttet (P = 0,01). Biogen anser att data från en del av ENGAGE stödjer resultaten från EMERGE, även om ENGAGE inte uppfyllde sitt primära effektmått. Biogen diskuterade därför med externa rådgivare och FDA om resultaten och dess innebörd.

I EMERGE, som nådde sitt förbestämda primära effektmått i den nya analysen, uppvisade patienter som behandlades med en hög dos av aducanumab en signifikant minskning av klinisk nedgång från baslinjen i CDR-SB-poäng efter 78 veckor (23 procent jämfört med placebo, P = 0,01).

I EMERGE visade patienter som behandlades med en hög dos aducanumab också en bestående minskning av klinisk nedgång mätt med de förutbestämda sekundära effektmåtten: Mini-Mental State Examination (MMSE; 15 % jämfört med placebo, P = 0,06), AD Assessment Scale-Cognitiv Subscale 13 items (ADAS-Cog 13; 27% jämfört med placebo,
P = 0,01), och AD-Cooperative Stud-Acitvities of Daily Living Inventory Mild Cognitive Impairmet Version (ADCS-ADL-MCI; 40% mot placebo, P = 0,001). Avbildningen av ansamlingar av amyloidplack i EMERGE visade att amyloidplackbördan minskades med låg och hög dos aducanumab jämfört med placebo efter 26 och 78 veckor (P <0,001). Ytterligare data från biomarkörer för taunivåer i cerebrospinalvätskan stödde dessa kliniska resultat. Biogen anser att data från patienter i ENGAGE som uppnådde tillräcklig exponering för en hög dos av aducanumab stödde resultaten från EMERGE.

I båda studierna var de vanligaste rapporterade biverkningarna amyloidrelaterade avvikelser avseende ödembildning (ARIA-E) och huvudvärk. Majoriteten av patienterna med ARIA-E upplevde inte symptom under ARIA-E-händelser, och ARIA-E-händelserna gick ofta över inom 4 till 16 veckor, vanligtvis utan långvariga kliniska följder. Biogen planerar att presentera ytterligare detaljer om den nya analysen av den större mängden data från EMERGE och ENGAGE vid CTAD-mötet i december 2019.

Efter att ha granskat uppgifterna i samråd med FDA, anser Biogen att skillnaden mellan resultaten från den nya analysen av den större mängden data och det resultat som förutspåddes av futilitetsanalysen till stor del berodde på patienternas högre exponering för en hög dos av aducanumab. Flera faktorer bidrog till den större exponeringen av aducanumab i den nya analysen med den större datamängden. Det inkluderar data med ett större antal patienter, en längre genomsnittlig exponering för hög dos, timingen för protokolländringar som möjliggjorde att en större andel patienter fick hög dos samt timing och förspecificerade kriterier för futilitetsanalysen.

Om Aducanumab

Aducanumab (BIIB037) är en human monoklonal antikropp som studeras för behandling av tidig Alzheimers sjukdom. Biogen licensierade aducanumab från Neurimmune enligt ett samarbets- och licensavtal. Sedan oktober 2017 har Biogen och Eisai samarbetat om aducanumab globalt.

EMERGE och ENGAGE var fas 3 multicenter, randomiserade, dubbelblinda, placebokontrollerade, parallellgruppstudier utformade för att utvärdera effektiviteten och säkerheten för aducanumab. Det primära syftet med studierna var att utvärdera effekten av månatliga doser av aducanumab jämfört med placebo för att minska kognitiv nedsättning och funktionsnedsättning mätt med förändringar i CDR-SB-poäng. Sekundära mål var att bedöma effekten av månatliga doser av aducanumab jämfört med placebo på klinisk nedgång mätt med MMSE, ADAS-Cog 13 och ADCS-ADL-MCI.

Kontakt: Mats Ekelund +46 76 182 36 27, mats.ekelund@biogen.com

​New analysis of larger dataset showed that aducanumab reduced clinical decline in patients with early Alzheimer’s disease as measured by the pre-specified primary and secondary endpoints

Based on discussions with the FDA, the Company plans to submit a Biologics License Application in early 2020

Biogen aims to offer aducanumab to eligible patients previously enrolled in clinical studies

The positive results of this new analysis were driven primarily by greater exposure to high dose aducanumab in the larger dataset as compared to data available at the time of the futility analysis

Cambridge, Mass. and Tokyo, Japan – October 22, 2019 – Biogen (Nasdaq: BIIB) and Eisai, Co., Ltd. (Tokyo, Japan) today announced that, after consulting with the U.S. Food and Drug Administration (FDA), Biogen plans to pursue regulatory approval for aducanumab, an investigational treatment for early Alzheimer’s disease (AD). The Phase 3 EMERGE Study met its primary endpoint showing a significant reduction in clinical decline, and Biogen believes that results from a subset of patients in the Phase 3 ENGAGE Study who received sufficient exposure to high dose aducanumab support the findings from EMERGE. Patients who received aducanumab experienced significant benefits on measures of cognition and function such as memory, orientation, and language. Patients also experienced benefits on activities of daily living including conducting personal finances, performing household chores such as cleaning, shopping, and doing laundry, and independently traveling out of the home. If approved, aducanumab would become the first therapy to reduce the clinical decline of Alzheimer’s disease and would also be the first therapy to demonstrate that removing amyloid beta resulted in better clinical outcomes.

The decision to file is based on a new analysis, conducted by Biogen in consultation with the FDA, of a larger dataset from the Phase 3 clinical studies that were discontinued in March 2019 following a futility analysis. This new analysis of a larger dataset that includes additional data that became available after the pre-specified futility analysis shows that aducanumab is pharmacologically and clinically active as determined by dose-dependent effects in reducing brain amyloid and in reducing clinical decline as assessed by the pre-specified primary endpoint Clinical Dementia Rating-Sum of Boxes (CDR-SB). In both studies, the safety and tolerability profile of aducanumab was consistent with prior studies of aducanumab.

“With such a devastating disease that affects tens of millions worldwide, today’s announcement is truly heartening in the fight against Alzheimer’s. This is the result of groundbreaking research and is a testament to Biogen’s steadfast determination to follow the science and do the right thing for patients,” said Michel Vounatsos, Chief Executive Officer at Biogen. “We are hopeful about the prospect of offering patients the first therapy to reduce the clinical decline of Alzheimer’s disease and the potential implication of these results for similar approaches targeting amyloid beta.”

Based on discussions with the FDA, the Company plans to file a Biologics License Application (BLA) in early 2020 and will continue dialogue with regulatory authorities in international markets including Europe and Japan. The BLA submission will include data from the Phase 1/1b studies as well as the complete set of data from the Phase 3 studies.

The Company aims to offer access to aducanumab to eligible patients previously enrolled in the Phase 3 studies, the long-term extension study for the Phase 1b PRIME study, and the EVOLVE safety study. Biogen will work towards this goal with regulatory authorities and principal investigators with a sense of urgency.

Study Results

EMERGE (1,638 patients) and ENGAGE (1,647 patients) were Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies designed to evaluate the efficacy and safety of two dosing regimens of aducanumab. These studies were discontinued on March 21, 2019, following the results of a pre-specified futility analysis which relied on an earlier and smaller dataset. The futility analysis was based on data available as of December 26, 2018, from 1,748 patients who had the opportunity to complete the 18-month study period and predicted that both studies were unlikely to meet their primary endpoint upon completion. Futility analyses are common in large clinical studies and use statistical modeling to attempt to predict the outcome of the studies based on a number of pre-specified assumptions and criteria.

Following the discontinuation of EMERGE and ENGAGE, additional data from these studies became available resulting in a larger dataset, which included a total of 3,285 patients, 2,066 of whom had the opportunity to complete the full 18 months of treatment. A new extensive analysis of this larger dataset showed a different outcome than the outcome predicted by the futility analysis. Specifically, the new analysis of this larger dataset showed EMERGE to be statistically significant on the pre-specified primary endpoint (P=0.01). Biogen believes that data from a subset of ENGAGE support the findings from EMERGE, though ENGAGE did not meet its primary endpoint. Biogen consulted with external advisors and the FDA on these different results and their implications.

“This large dataset represents the first time a Phase 3 study has demonstrated that clearance of aggregated amyloid beta can reduce the clinical decline of Alzheimer’s disease, providing new hope for the medical community, the patients, and their families,” said Dr. Anton Porsteinsson, William B. and Sheila Konar Professor of Psychiatry, Neurology and Neuroscience, director of the University of Rochester Alzheimer's Disease Care, Research and Education Program (AD-CARE), and principal investigator. “There is tremendous unmet medical need, and the Alzheimer’s disease community has been waiting for this moment. I commend Biogen, the FDA, the medical community, and the patients and their study partners for their persistence in working to make today’s announcement a reality.”

In EMERGE, which met its pre-specified primary endpoint in the new analysis, patients treated with high dose aducanumab showed a significant reduction of clinical decline from baseline in CDR-SB scores at 78 weeks (23% versus placebo, P=0.01). In EMERGE, patients treated with high dose aducanumab also showed a consistent reduction of clinical decline as measured by the pre-specified secondary endpoints: the Mini-Mental State Examination (MMSE; 15% versus placebo, P=0.06), the AD Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13; 27% versus placebo, P=0.01), and the AD Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI; 40% versus placebo, P=0.001). Imaging of amyloid plaque deposition in EMERGE demonstrated that amyloid plaque burden was reduced with low and high dose aducanumab compared to placebo at 26 and 78 weeks (P<0.001). Additional biomarker data of tau levels in the cerebrospinal fluid supported these clinical findings. Biogen believes that data from patients in ENGAGE who achieved sufficient exposure to high dose aducanumab supported the findings of EMERGE.

In both studies, the most commonly reported adverse events were amyloid-related imaging abnormalities-edema (ARIA-E) and headache. The majority of patients with ARIA-E did not experience symptoms during the ARIA-E episode, and ARIA-E episodes generally resolved within 4 to 16 weeks, typically without long-term clinical sequelae. Biogen plans to present further detail on the new analysis of the larger dataset from EMERGE and ENGAGE at the Clinical Trials on Alzheimer's Disease (CTAD) meeting in December 2019.

After reviewing the data in consultation with the FDA, Biogen believes that the difference between the results of the new analysis of the larger dataset and the outcome predicted by the futility analysis was largely due to patients’ greater exposure to high dose aducanumab. Multiple factors contributed to the greater exposure to aducanumab in the new analysis of the larger dataset, including data on a greater number of patients, a longer average duration of exposure to high dose, the timing of protocol amendments that allowed a greater proportion of patients to receive high dose, and the timing and pre-specified criteria of the futility analysis.

Biogen Conference Call and Webcast

On October 22, 2019, at 8:00 a.m. ET, Biogen will host its third quarter 2019 earnings conference call, which will include a discussion of the new analysis of the larger dataset from the Phase 3 studies of aducanumab. This conference call will be broadcast via the internet and will be accessible through the Investors section of Biogen’s website, www.biogen.com. Following the live webcast, an archived version of the call will be available on the website. Supplemental information in the form of a slide presentation is also accessible at the same location on the internet and will be subsequently available on the website for at least one month.

About Aducanumab

Aducanumab (BIIB037) is an investigational human monoclonal antibody studied for the treatment of early Alzheimer’s disease. Biogen licensed aducanumab from Neurimmune under a collaborative development and license agreement. Since October 2017 Biogen and Eisai have collaborated on the development and commercialization of aducanumab globally.

EMERGE and ENGAGE were Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies designed to evaluate the efficacy and safety of aducanumab. The primary objective of the studies was to evaluate the efficacy of monthly doses of aducanumab as compared with placebo in reducing cognitive and functional impairment as measured by changes in the CDR-SB score. Secondary objectives were to assess the effect of monthly doses of aducanumab as compared to placebo on clinical decline as measured by MMSE, ADAS-Cog 13, and ADCS-ADL-MCI.

About Biogen

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics, and is focused on advancing research programs in multiple sclerosis and neuroimmunology, neuromuscular disorders, movement disorders, Alzheimer’s disease and dementia, ophthalmology, immunology, neurocognitive disorders, acute neurology, and pain.

We routinely post information that may be important to investors on our website at www.biogen.com. To learn more, please visit www.biogen.com and follow us on social media – Twitter, LinkedIn, Facebook, YouTube.

About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. Eisai’s corporate philosophy is to give first thought to patients and their families, and to increase the benefits that health care provides to them. Under this philosophy, the company endeavors to become a human health care (hhc) company. With approximately 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to address unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.

Leveraging the experience gained from the development and marketing of Aricept® (donepezil), a treatment for Alzheimer’s disease and dementia with Lewy bodies, Eisai has been working to establish a social environment that involves patients in each community in cooperation with various stakeholders including the government, healthcare professionals and care workers, and is estimated to have held over ten thousand dementia awareness events worldwide. As a pioneer in the field of dementia treatment, Eisai is striving to not only develop next generation treatments but also to develop diagnosis methods and provide solutions.

For more information about Eisai Co., Ltd., please visit www.eisai.com.

Biogen Safe Harbor
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about additional results from the Phase 3 clinical studies of aducanumab; the potential clinical effects of aducanumab; the potential benefits, safety, and efficacy of aducanumab; potential regulatory discussions, submissions, and approvals and the timing thereof; clinical development programs, clinical trials, data readouts, and presentations related to aducanumab; the enrollment of any future clinical studies of aducanumab; the treatment of AD; the potential of Biogen’s commercial business and pipeline programs, including aducanumab; the anticipated benefits and potential of Biogen’s collaboration arrangements with Eisai; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would,” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation actual timing and content of submissions to and decisions made by the regulatory authorities regarding aducanumab; regulatory submissions may take longer or be more difficult to complete than expected; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of Biogen’s drug candidates, including aducanumab; actual timing and enrollment of future studies of aducanumab; the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis; risks of unexpected costs or delays; the risks of other unexpected hurdles; uncertainty of success in the development and potential commercialization of aducanumab; failure to protect and enforce Biogen’s data, intellectual property, and other proprietary rights and uncertainties relating to intellectual property claims and challenges; risks relating to the potential launch of aducanumab, including preparedness of healthcare providers to treat patients, the ability to obtain and maintain adequate reimbursement for aducanumab, and other unexpected difficulties or hurdles; product liability claims; and third party collaboration risks. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogen’s expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in Biogen’s most recent annual or quarterly report and in other reports it has filed with the U.S. Securities and Exchange Commission. These statements are based on Biogen’s current beliefs and expectations and speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

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MEDIA CONTACTS:

Mats Ekelund

+46 76 182 36 27

mats.ekelund@biogen.com

• ​DEVOTE studien undersöker säkerhet och potentiellt ökad effekt med en högre dos SPINRAZA vid behandling av SMA
• Långtidsdata från SHINE studien visar förbättringar eller stabilisering av motoriska funktioner för patienter behandlade med Spinraza upp till 21 års ålder under upp till 6 års tid.

Cambridge, Mass.,Sept. 18, 2019 –Biogen Inc. (Nasdaq: BIIB) today announced updates to the SPINRAZA (nusinersen) clinical development program including the initiation of a new global clinical trial, DEVOTE. The DEVOTE study will evaluate if a higher dose of nusinersen can provide increased efficacy in the treatment of spinal muscular atrophy (SMA) across a broad patient population. In addition, new data further demonstrating the safety and efficacy of treatment with nusinersen in individuals with later-onset SMA will be featured in a podium presentation at the 13^th Congress of the European Paediatric Neurology Society (EPNS) in Athens (September 17-21).

New study, DEVOTE, to evaluate if SPINRAZA can offer increased efficacy in treating SMA
​Building on the long-term safety profile and efficacy of nusinersen in a broad range of patients, the DEVOTE trial will examine the potential for increased efficacy, as well as the safety and tolerability of nusinersen, when administered at a higher dose. The trial is a Phase 2/3 randomized, controlled dose-escalating study that will be conducted at 50 sites around the world with a projected enrollment of 126 individuals with SMA of all ages, including adults.

The three-part trial will include an open-label safety evaluation and a pivotal, double-blind, active control randomized treatment period followed by an open-label treatment period. After the safety evaluation, the trial will compare two loading doses of 50 milligrams (mg) 15 days apart followed by a maintenance dose of 28 mg every four months with the current U.S. Food and Drug Administration-approved administration of nusinersen, which is four loading doses with 12 mg maintenance doses every four months. The third part of the trial will be an open-label evaluation to determine how to safely and efficiently transition patients from the currently approved dose of SPINRAZA to the higher dose being tested in the study.

More information on the trial (NCT04089566) is available at clinicaltrials.gov.

Data to be presented at EPNS demonstrate improvements or stabilization in motor function following longer-term treatment

An integrated analysis from SHINE (NCT02594124), an open-label extension study for patients with SMA who participated in prior nusinersen studies, found that children with later-onset SMA (Type 2 or Type 3) experienced improvements or stabilization in one or more measures of motor function for up to nearly six years, in contrast to the expected decline observed in natural history cohorts. SHINE is following 24 patients aged 2-15 at treatment initiation (SMA Type 2; n=10 and Type 3; n=14) who transitioned from the CS2/CS12 studies, which previously showed that individuals with later-onset SMA who were treated with nusinersen demonstrated improvements in motor function and disease stabilization over approximately three years, that were not observed in natural history cohorts.¹ Patients in the study were between 7 and 21 years old at the last study visit.

Motor function measures in this analysis of the SHINE study included the Hammersmith Functional Motor Scale–Expanded (HFMSE), Upper Limb Module (ULM), and Six-Minute Walk Test (6MWT). No participants discontinued treatment due to adverse events, and no new safety concerns were identified during the nearly six-year follow-up period.

“These findings are important in understanding the need for long-term treatment in individuals with SMA,” said Basil Darras, M.D., lead study author, director of the Neuromuscular Center and Spinal Muscular Atrophy Program at Boston Children’s Hospital, and professor of neurology at Harvard Medical School. “These data reinforce the long-term safety and durability of SPINRAZA to improve or stabilize motor function in individuals with later-onset SMA.”

Om Spinraza
​Spinraza är avsett för behandling av spinal muskelatrofi av typ 5q. Biverkningar som observerats är fall av allvarlig infektion, såsom meningit. Det har även förekommit rapporter om kommunicerande hydrocefalus, aseptisk meningit och överkänslighet (t.ex. angioödem, urtikaria och hudutslag). För information om kontraindikationer, varningar och försiktighet, biverkningar, dosering och förpackningar se www.fass.se.

About Biogen
​At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp, and today has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, neuromuscular disorders, movement disorders, Alzheimer’s disease and dementia, ophthalmology, immunology, neurocognitive disorders, acute neurology and pain.

Biogen Safe Harbor
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential benefits, safety and efficacy of SPINRAZA; the results of certain real-world data; the identification and treatment of SMA; our research and development program for the treatment of SMA; the clinical development program for SPINRAZA, including the enrollment of the DEVOTE study; the potential benefits and results from early treatment of SMA; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. You should not place undue reliance on these statements, or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation risks relating to the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; failure to obtain regulatory approvals in other jurisdictions; risks of unexpected costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges;; regulatory authorities may require additional information or further studies; product liability claims; and third party collaboration risks. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports, we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

References

1Darras BT, Chiriboga CA, Iannaccone ST, et al. Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies. Neurology. 2019 May 21;92(21):e2492-e2506.

2Finkel R, Chiriboga C, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017-3026.

3 Darras B, Markowitz J, Monani U, De Vivo D. Chapter 8 - Spinal Muscular Atrophies. In: Vivo BTD, ed. Neuromuscular Disorders of Infancy, Childhood, and Adolescence (Second Edition). San Diego: Academic Press; 2015:117-145.

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MEDIA CONTACTS:

Mats Ekelund

+46 76 182 36 27

mats.ekelund@biogen.com​

• ​Det positiva utlåtandet grundas på data från över 1000 graviditeter
• Data indikerar inte någon ökad risk för allvarliga medfödda defekter efter interferon beta exponering före befruktning och/eller under första trimestern.
• Data visar att utfallen från graviditeterna ligger i linje med utfallen för graviditeter i den allmänna befolkningen

Cambridge, Mass. – September 23, 2019 Biogen Inc. (Nasdaq: BIIB) today announced that the Committee for Medicinal Products for Human Use (CHMP), part of the of the European Medicines Agency (EMA), recommended an update to marketing authorizations of approved interferon beta treatments, including Plegridy^® (peginterferon beta-1a) and Avonex^® (interferon beta-1a), to remove pregnancy contraindications and, where clinically needed, to allow use during pregnancy and breastfeeding in women with relapsing multiple sclerosis (MS).

“Women are diagnosed with MS at least two to three times more frequently than men,[1] and the disease may strike during their child-bearing years.[2] Choosing a treatment plan that allows women to continue or start their MS therapy while pregnant or breastfeeding is a step forward for those living with this chronic, debilitating disease and their partners,” said Alfred Sandrock, Jr., M.D., Ph.D., executive vice president and chief medical officer at Biogen. “This CHMP opinion gives physicians and their patients added confidence when considering treatment with Plegridy or Avonex, two therapy options for relapsing MS that have been prescribed to more than half a million people living with the disease.”

The CHMP opinion is based on data from the European Interferon Beta Pregnancy Registry, as well as the national health registers in Finland and Sweden, which together created the largest cohort studies providing safety data related to interferon beta exposure in women of child-bearing age with MS.

Data collected from more than 1,000 pregnancy outcomes from registries and post-marketing experience indicate no increased risk of major congenital anomalies following exposure to interferon beta before conception or during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment was likely interrupted when the pregnancy was detected and/or confirmed. Additionally, experience with exposure in the second and third trimesters is very limited. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far.Limited data suggest the levels of interferon beta-1a excreted in human milk are negligible, and no harmful effects on the breastfed newborn/infant are anticipated.

Om Plegridy

Plegridy är avsett för vuxna patienter för behandling av skovvis förlöpande multipel skleros, vilket är den vanligaste formen av multipel skleros. De vanligaste biverkningarna, i kliniska studier, var erytem vid injektionsstället och influensaliknande symtom. Fertila kvinnor ska använda effektiv preventivmetod. För ytterligare information om förpackningar, kontraindikationer, varningar och försiktighet, biverkningar och pris, se www.fass.se

Om Avonex

Avonex är avsett för vuxna patienter för behandling av skovvis förlöpande multipel skleros, vilket är den vanligaste formen av multipel skleros. Den vanligaste biverkningen, i kliniska studier var influensaliknande symtom. Kvinnor i fertil ålder skall använda lämpliga preventivmetoder. För ytterligare information om förpackningar, kontraindikationer, varningar och försiktighet, biverkningar och pris, se www.fass.se

About BiogenAt Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp, and today has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, neuromuscular disorders, movement disorders, Alzheimer’s disease and dementia, ophthalmology, immunology, neurocognitive disorders, acute neurology and pain.

Biogen Safe Harbor

This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential benefits, safety and efficacy of PLEGRIDY and AVONEX; the results of certain real-world data; our research and development program for the treatment of MS; plans for additional regulatory filings in other jurisdictions; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “except,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation the occurrence of adverse safety eventsand/or unexpected concerns that may arise from additional data or analysis; failure to obtain regulatory approvals in other jurisdictions; regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of expansion of product labeling; risks of unexpected costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; and product liability claims. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

[1] Multiple Sclerosis Coalition. The Use of Disease-modifying Therapies in Multiple Sclerosis Principles and Current Evidence. Updated March 2017. http://www.nationalmssociety.org/getmedia/1e64b96c-9e55-400e-9a64-0cdf5e2d60fe/summaryDMTpaper_-final

[2] Coyle PK. Pregnancy and multiple sclerosis. Neurol Clin. 2012 Aug;30(3):877-88. doi: 10.1016/j.ncl.2012.05.002. Epub 2012 Jun 22.

MEDIA CONTACTS:

Mats Ekelund

+46 76 182 36 27

mats.ekelund@biogen.com

​

Cambridge, Mass. – September 13, 2019 – Biogen Inc. (Nasdaq: BIIB) is highlighting new data that demonstrate the potential benefits of treatment with NATALIZUMAB, PEGINTERFERON BETA-1A and INTERFERON BETA-1A in specific multiple sclerosis (MS) patient populations. Results obtained in real-world clinical practice are being presented at the 35^th Congress of the European Committee for Treatment and 24^th Annual Conference of Rehabilitation in MS in Stockholm (September 11-13).

“Biogen’s long-standing leadership in MS presents an opportunity to continue evolving the paradigm of care through continued research of some of our most widely prescribed MS therapies, including NATALIZUMAB, PEGINTERFERON BETA-1A and INTERFERON BETA-1A,” said Alfred Sandrock, Jr., M.D., Ph.D., executive vice president and chief medical officer at Biogen. “Through exploration of potential new approaches, like NATALIZUMAB extended interval dosing, we are working to optimize patient outcomes.”

Data Further Support Early Treatment with NATALIZUMAB and Extended Interval Dosing

Four-year data from the observational, open-label, single-arm STRIVE study support the real-world long-term effectiveness of NATALIZUMAB in patients with early relapsing MS, who are within three years from diagnosis and are anti-JC virus antibody negative. Over the first two to four years of treatment (N=110/157), 70.1 percent of patients in the study achieved clinical NEDA (no evidence of disease activity), defined as no relapses or 24-week confirmed disability worsening. Additionally, 83.7 percent achieved MRI NEDA, defined as no gadolinium-enhancing or new/newly enlarging T2 lesions, and more than half (58%) achieved overall NEDA, which encompassed both clinical and MRI NEDA. Results also show NATALIZUMAB was associated with significant improvements in disability and cognitive performance.

The effectiveness of every six weeks (Q6W) dosing with natalizumab was evaluated using data from the NATALIZUMAB Observational Program (TOP), an ongoing, real-world study of natalizumab-treated patients. Analyses compared relapse outcomes in patients who switched to natalizumab Q6W dosing after at least one year on every four weeks (Q4W) dosing to those who remained on the approved Q4W dosing.After propensity score matching, results indicate there was no significant difference in annualized relapse rate or risk of relapse between the two groups. These data complement the previously presented TOUCH database safety analysis showing that natalizumab extended interval dosing (EID; average of approximately six weeks) was associated with a significantly lower risk of the rare but serious brain infection progressive multifocal leukoencephalopathy (PML), compared to Q4W dosing. Biogen recently completed enrollment for the Phase 3b NOVA study, a two-year, randomized, prospective trial that will compare the effectiveness of natalizumab Q4W versus Q6W after at least one year of Q4W dosing.

Real-World Data Indicate Interferon Beta Treatment May Not Impact Pregnancy/Infant Outcomes

As women with MS are often diagnosed and treated at child-bearing age, family planning is frequently an important consideration for physicians and patients when choosing a treatment path. New data from two real-world observational studies provide further support that exposure to interferon beta treatment, including PEGINTERFERON BETA-1A and INTERFERON BETA-1A,before conception and/or during pregnancy has no adverse effect on pregnancy or infant growth outcomes.

Researchers utilized healthcare data from Nordic registers (Finland and Sweden) to investigate infant outcomes for women with MS treated with interferon beta compared to women with MS unexposed to disease-modifying therapies. Results show outcomes were similar between the two groups, with no evidence that exposure to interferon beta treatment before and/or during pregnancy affected the weight or head circumference of infants at birth. Data on pregnancy outcomes collected during the ongoing five-year PEGINTERFERON BETA-1A Observational Program (POP), which is evaluating the long-term safety and effectiveness of PEGINTERFERON BETA-1A in more than 1,200 relapsing MS patients worldwide, were consistent with previously reported pregnancy outcomes from both the Nordic registers study and the European Interferon Beta Pregnancy Registry.

Featured data presentation details:

• Natalizumab is Associated with No Evidence of Disease Activity and with Improvement in Disability and Cognitive Performance in Anti–JC Virus Seronegative Patients with Early Relapsing-Remitting Multiple Sclerosis: STRIVE 4-Year Results (P1348; Poster Session 3, Friday, September 13, 12:15-2:15 p.m. CET)
• No Significant Difference in Relapse Outcomes in Patients Switching to Natalizumab Extended Interval Dosing or Remaining on Standard Interval Dosing: Propensity Score Comparative Effectiveness Analysis of Patients in the NATALIZUMAB Observational Program (P1033, Poster Session 2, Thursday, September 12, 5:15-7:15 p.m. CET)
• Prevalence of Infant Outcomes at Birth After Exposure to Interferon Beta Prior to or During Pregnancy: A Register-based Cohort Study in Finland and Sweden Among Women with MS (P1144; Poster Session 3, Friday, September 13, 12:15-2:15 p.m. CET)
• Safety, Pregnancy Outcomes, and Clinical Effectiveness of Peginterferon Beta-1a for Patients with Newly Diagnosed and Non-Newly Diagnosed Relapsing Multiple Sclerosis: Third Interim Analysis of the Peginterferon beta-1a Observational Program (P1019; Poster Session 3, Friday, September 13, 12:15-2:15 p.m. CET)

Om TYSABRI

Natalizumab är indicerat i monoterapi hos vuxna med mycket aktiv skovvis förlöpande multipel skleros (MS), för följande patientgrupper: Patienter med mycket aktiv sjukdom trots fullständig och adekvat behandling med minst en sjukdomsmodifierande behandling; eller patienter med snabb utveckling av svår RRMS, definierat som två eller flera funktionsnedsättande skov under ett år eller en eller flera Gd+ lesioner vid MRT eller en avsevärd ökning av T2-lesioner jämfört med nyligen utförd MRT.

Natalizumab är kontraindicerat hos patienter med: progressiv multifokal leukoencefalopati (PML), förhöjd risk för opportunistiska infektioner (inklusive nedsatt immunförsvar), aktiva maligniteter (undantaget basalcellscancer i huden) samt i kombination med andra sjukdomsmodifierande behandlingar.

Behandling med natalizumab har förknippats med en förhöjd risk för PML (progressiv multifokal leukoencefalopati) som orsakas av JC-virus. Följande riskfaktorer är förknippade med en ökad risk för PML: förekomst av anti-JCV-antikroppar; Behandling efter 2 år; användning av immunosuppressiva medel före behandling med natalizumab. Nyttan och riskerna med natalizmab-behandling ska utvärderas regelbundet. Patienten bör upplysas om tidiga tecken och symtom på PML.

Före start av behandling med natalizumab måste en nyligen genomförd (vanligen inom ca tre månader) undersökning med MRT finnas tillgänglig som en referens och upprepas minst årligen. Mer frekventa MRT-undersökningar ska övervägas för patienter som löper en högre risk att drabbas av PML.

För information om kontraindikationer, varningar och försiktighet, biverkningar, dosering, pris och förpackning se www.fass.sewww.fass.sewww.fass.sewww.fass.se

Om PLEGRIDY

Plegridy är avsett för vuxna patienter för behandling av skovvis förlöpande multipel skleros, vilket är den vanligaste formen av multipel skleros. De vanligaste biverkningarna, i kliniska studier, var erytem vid injektionsstället och influensaliknande symtom. Fertila kvinnor ska använda effektiv preventivmetod. För ytterligare information om förpackningar, kontraindikationer, varningar och försiktighet, biverkningar och pris, se www.fass.se

Om AVONEX

Avonex är avsett för vuxna patienter för behandling av skovvis förlöpande multipel skleros, vilket är den vanligaste formen av multipel skleros. Den vanligaste biverkningen, i kliniska studier var influensaliknande symtom. Kvinnor i fertil ålder skall använda lämpliga preventivmetoder. För ytterligare information om förpackningar, kontraindikationer, varningar och försiktighet, biverkningar och pris, se www.fass.se

About BiogenAt Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp, and today has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics, and is focused on advancing research programs in multiple sclerosis and neuroimmunology, neuromuscular disorders, movement disorders, Alzheimer’s disease and dementia, ophthalmology, immunology, neurocognitive disorders, acute neurology, and pain.

Biogen Safe Harbor

This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to the potential benefits, safety and efficacy of NATALIZUMAB, PEGINTERFERON BETA-1A and INTERFERON BETA-1A; potential clinical effects of NATALIZUMAB, PEGINTERFERON BETA-1A and INTERFERON BETA-1A; the results of certain real-world data; the clinical development program for natalizumab; clinical trial results and plans; our research and development program for the treatment of MS; the treatment of MS; the potential of our commercial business; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “except,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis; risks of unexpected costs or delays; regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our products and expansion of product labeling; unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; and product liability claims. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

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MEDIA CONTACTS:

Mats Ekelund

+46 76 182 36 27

mats.ekelund@biogen.com

Cambridge, Mass. – September 13, 2019 – Biogen Inc. (Nasdaq: BIIB) announced new data to support the consistent, long-term benefits of treatment with dimethyl fumarate over 10 years, as well as additional diroximel fumarate data that further characterize the tolerability profile of this investigational oral fumarate for relapsing multiple sclerosis (MS). These findings are being presented at the 35^th Congress of the European Committee for Treatment and Research in MS (ECTRIMS) and 24^th Annual Conference of Rehabilitation in MS in Stockholm (September 11-13).

“Biogen’s new data underscore the role of dimethyl fumarate as a option for relapsing MS, with many patients in the study experiencing no relapses or progression in their disability over a 10-year period,” said Alfred Sandrock, Jr., M.D., Ph.D., executive vice president and chief medical officer at Biogen. “We are proud of the legacy dimethyl fumarate has achieved over the years and are excited to continue building our franchise of fumarate products with the potential addition of diroximel fumarate. Diroximel fumarate offers a differentiated gastrointestinal tolerability profile and, if approved, will be a potential choice for physicians and patients with relapsing MS to consider.”

The dimethyl fumarate 10-Year Data

New results from the ongoing Phase 3 ENDORSE extension study reinforce the long-term effectiveness and safety of continuous DIMETHYL FUMARATE treatment over a decade. The analysis, included participants (N= 192) with at least 10 years of follow up. Results show that approximately half (51 percent) of patients remained relapse-free over the study period. In addition, 64 percent of patients had no confirmed disability progression over the study period, and patients generally maintained the ability to walk without significant disability (79 percent). The safety profile of DIMETHYL FUMARATE was consistent over 10 years, with no increased occurrence of serious infections.

Separately, a meta-analysis of real-world evidence to compare the effectiveness of DIMETHYL FUMARATE versus other disease-modifying therapies for relapsing MS is also being presented. The meta-analysis analyzed data from 18 databases of large real-world studies and found that DIMETHYL FUMARATE was significantly more effective than interferon beta, glatiramer acetate and teriflunomide in reducing annualized relapse rate and delaying time to first relapse. DIMETHYL FUMARATE demonstrated comparable effectiveness to fingolimod and was less effective than natalizumab and alemtuzumab. These results are consistent with previously reported comparative effectiveness data.

Data Support Diroximel Fumarate as a Potential New Option for Relapsing MS

Updated interim data from the Phase 3 EVOLVE-MS-1 study support the potential of Biogen and Alkermes’ investigational treatment, diroximel fumarate, as a novel oral fumarate. EVOLVE-MS-1 is an ongoing, single-arm, open-label, two-year study evaluating the safety and exploring the efficacy of diroximel fumarate in patients with relapsing-remitting MS and has enrolled approximately 1,000 patients. The interim results, which included data from 888 patients treated with diroximel fumarate for a median of approximately 18 months, corroborate previous data indicating diroximel fumarate is generally well-tolerated in people with relapsing MS.

In the study, most adverse events were mild to moderate in nature. 16.3 percent of treatment discontinuation were reported overall, with less than 1 percent of patients discontinuing diroximel fumarate treatment due to gastrointestinal (GI) side effects. These data are further supportive of recently reported topline results from the elective Phase 3 EVOLVE-MS-2 study, in which diroximel fumarate demonstrated statistically superior GI tolerability compared to DIMETHYL FUMARATE based on patient-reported outcomes.

Exploratory efficacy results from EVOLVE-MS-1 suggest diroximel fumarate significantly reduced annualized relapse rate by 79.4 percent and the mean number of gadolinium-enhancing lesions by 64.3 percent compared to baseline over 18 months, with similar results observed in newly diagnosed patients.

Featured data presentation details:

• Overall Safety and Efficacy Through 10 Years of Treatment with Delayed-release Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis (P1397; Poster Session 3, Friday, September 13, 12:15-2:15 pm CET)
• Comparative Effectiveness of Delayed-release Dimethyl Fumarate vs. Other Disease-modifying Therapies in Patients with Multiple Sclerosis: A Network Meta-analysis of Real-world Evidence (P1394; Poster Session 3, Friday, September 13, 12:15-2:15 pm CET)
• Diroximel Fumarate (DRF) in Patients with Relapsing-Remitting Multiple Sclerosis: Interim Safety and Efficacy Results from the Phase 3 EVOLVE-MS-1 Study (ePoster; available for duration of congress)

Om TECFIDERA® (dimetylfumarat)
Dimetylfumarat är en oral behandling för vuxna patienter med skovvis förlöpande multipel skleros, vilket är den vanligaste formen av multipel skleros. De vanligaste biverkningarna, i kliniska studier, var hudrodnad och gastrointestinala biverkningar. Dimetylfumarat rekommenderas inte under graviditet eller till fertila kvinnor som inte använder lämpliga preventivmedel. Sällsynta fall av progressiv multifokal leukoencefalopati (PML) har förekommit. För ytterligare information om förpackningar, kontraindikationer, varningar och försiktighet, biverkningar och pris, se www.fass.se

About Diroximel Fumarate
Diroximel fumarate is an investigational, novel oral fumarate candidate in development for the treatment of relapsing forms of MS. Diroximel fumarate is designed to rapidly convert to monomethyl fumarate in the body and, based on bioequivalence data, is referencing DIMETHYL FUMARATE as part of the 505(b)(2) regulatory pathway in the United States.

About BiogenAt Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp, and today has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics, and is focused on advancing research programs in multiple sclerosis and neuroimmunology, neuromuscular disorders, movement disorders, Alzheimer’s disease and dementia, ophthalmology, immunology, neurocognitive disorders, acute neurology, and pain.

Biogen Safe Harbor

This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to the potential benefits, safety and efficacy of DIMETHYL FUMARATE and diroximel fumarate; potential clinical effects of DIMETHYL FUMARATE and diroximel fumarate; potential regulatory approval and the timing thereof; the results of certain real-world data; the clinical development program for diroximel fumarate; clinical trial results and plans; the potential of our commercial business and pipeline programs, including diroximel fumarate; the anticipated benefits and potential of our collaboration arrangements with Alkermes; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “except,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis; risks of unexpected costs or delays; regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates, including diroximel fumarate; actual timing and content of submissions to and decisions made by the regulatory authorities regarding our drug candidates, including diroximel fumarate; regulatory submissions may take longer or be more difficult to complete than expected; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; uncertainty of success in the development and potential commercialization of VUMERITY; risks relating to the potential launch of VUMERITY, including preparedness of healthcare providers to treat patients, the ability to obtain and maintain adequate reimbursement for VUMERITY and other unexpected difficulties or hurdles; product liability claims; and third party collaboration risks. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

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MEDIA CONTACTS:

Mats Ekelund

+46 76 182 36 27

mats.ekelund@biogen.com

Läkemedelsföretaget Biogen inleder ett samarbete med H2 Health Hub, en innovationshub inom digital hälsa. Samarbetet syftar till att knyta nära band mellan Biogen och H2 Health Hubs medlemmar för att tillsammans lära om och driva utvecklingen av hur patientnära, digitala hälsotjänster och produkter implementeras i människors vardag.

– Biogen är ett innovativt forskningsinriktat företag som är nyfiket på och öppet för det som händer inom digitalisering och artificiell intelligens. Vi står inte bara i ett labb och forskar om molekyler, vi ser bredare på läkemedel och deras plats i sjukvården och där ser vi att det finns kopplingar till den övriga utvecklingen, säger Mats Ekelund, nordiskt ansvarig för hälsoekonomi på Biogen.

H2 Health Hub är Nordens ledande innovationshub inom digital hälsa där entreprenörer, bolag, beslutsfattare, forskare och andra tillsammans skapar framtidens hälsolösningar. De drygt 40 startup-bolag som redan sitter på H2 jobbar bland annat med artificiell intelligens, big data, sensorer och virtual reality,VR, för att skapa tjänster som gör hälsa tillgänglig och personligt anpassad.

– Digitalisering och artificiell intelligens är de två krafter som är viktigast för att förändra hälso- och sjukvården just nu. Vi ser att det leder till förändringar både när det gäller hur sjukvården är utformad, hur patienterna involveras och för att förbättra screening, diagnosticering och behandling, säger Mats Ekelund.

– Jag tror att det finns en enorm patientnytta att uppnå med digitaliseringen. Det kan dels stärka patientens nytta i kontakten med hälso- och sjukvården. Bara en sådan sak som att digitaliseringen innebär att patienten delar information om sig själv kan leda till att vi kan hjälpa till att förbättra och erbjuda lösningar som är mer skräddarsydda. Det kan också underlätta forskningen och öka kunskapen kring vilken effekt som läkemedel har på olika patienter.

Mats Ekelund konstaterar att utvecklingen på läkemedelsområdet alltmer går mot specialistläkemedel.

– Här det viktigt att hitta rätt patienter, att patienterna har rätt diagnos och att de följer den ordinerade behandlingen. Här kan den nya teknologin hjälpa till.

– Genom samarbete med globala bolag som Biogen, kan smarta lösningar från startups på H2 Health Hub snabbare få en större spridning och nå fler patienter, säger Paul Beatus, grundare av H2 Health Hub.

Kontakt:

Mats Ekelund, Nordic Value & Access Director Market Access

Biogen Sweden AB

mats.ekelund@biogen.com

tel: +46 76 182 36 27

Paul Beatus, CEO & Co-founder H2 Health Hub

paul@h2healthhub.com

www.h2healthhub.com

tel: +46 76 2569953