`
`New Data Show Strong, Sustained Effects of
`TECFIDERA® (Dimethyl Fumarate) in Newly-Diagnosed
`and Early Disease Course Multiple Sclerosis Patients
`Release Date:
`Wednesday, October 7, 2015 6:00 am EDT
`Terms:
`Neurodegenerative diseases [1]
`Dateline City:
`CAMBRIDGE, Mass.
`− TECFIDERA Significantly Reduced MS Inflammatory Disease Activity
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`− − L
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`ong-Term Efficacy and Safety of TECFIDERA Demonstrated in Six-
`Year Data from ENDORSE Study −
`
`CAMBRIDGE, Mass.--(BUSINESS WIRE [2])--Biogen [3] (NASDAQ: BIIB) will present new data that reinforce the proven efficacy
`and well-established safety profile of TECFIDERA® (dimethyl fumarate) in a broad range of people with relapsing-remitting
`multiple sclerosis (RRMS) at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis
`(ECTRIMS) in Barcelona, Spain (7-10 October). The data show that TECFIDERA significantly reduced multiple sclerosis (MS)
`relapses and delayed disability progression in patients who are newly diagnosed and those early in their disease course;
`these effects were sustained over six years of follow-up.
`New data at ECTRIMS also include a post-hoc analysis in which TECFIDERA significantly reduced key inflammatory disease
`outcomes compared to glatiramer acetate (GA)1 and, in a separate analysis, TECFIDERA demonstrated a favorable benefit-
`risk profile throughout six years of follow-up from the ENDORSE study.
`“The benefits of taking a strong, efficacious therapy early in the disease course have been shown to improve a patient’s
`long-term prognosis when treatment is initiated before MS has advanced and caused irreparable damage,” said Ralf Gold,
`M.D., professor and chair of the Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum. “The data at ECTRIMS
`demonstrate that patients initiating treatment with TECFIDERA early in their disease experienced significant reductions in
`relapse rates and disability progression over time compared to those taking placebo.”
`Strong Efficacy in Early MS Patients
`An analysis of the Phase 3 DEFINE and CONFIRM studies shows that TECFIDERA had significant effects on clinical outcomes in
`RRMS patients who initiated treatment early in their disease course, defined as those patients with a baseline Expanded
`Disability Status Scale (EDSS) score of ≤2.0 (indicating minimal to no disability). Compared to patients treated with placebo,
`TECFIDERA reduced annualized relapse rate (ARR) by 63 percent (p<0.0001) and reduced risk of 12-week confirmed disability
`progression by 40 percent (p=0.0066).
`Reductions in Inflammatory Disease Outcomes
`A post-hoc analysis of the MRI population from the Phase 3 CONFIRM study found that TECFIDERA significantly reduced key
`inflammatory disease outcomes compared to GA (20 mg subcutaneous daily injection). CONFIRM investigated TECFIDERA
`against placebo and included a reference comparator arm of GA versus placebo.
`In this analysis, inflammatory disease activity was measured using a novel composite endpoint that included the presence of
`relapses, gadolinium-enhancing (Gd+) lesions and new or newly enlarging T2 lesions. An event was defined as a relapse, Gd+
`lesion or new/newly enlarging T2 lesion occurring within a specified time interval over two years (weeks 0−24, 24−48, or
`48−96). Patients were considered free of inflammatory disease activity if they did not experience an event within a given
`interval or any preceding intervals, and were evaluated for inflammatory disease activity as long as they were known to be at
`risk.
`Results show that a higher proportion of TECFIDERA patients were free of inflammatory disease activity at all time intervals
`over two years:
`36 percent of TECFIDERA patients compared to 29 percent of GA patients during weeks 0–24
`34 percent of TECFIDERA patients compared to 23 percent of GA patients during weeks 24–48
`21 percent of TECFIDERA patients compared to 16 percent of GA patients during weeks 48–96
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`Page 1 of 3
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`Biogen Exhibit 2081
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`IPR2015-01993
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`The overall hazard ratio (HR) (95% confidence interval [CI]) for TECFIDERA compared to GA was 0.77 (0.59−0.99; p=0.0446),
`and the overall HR (95% CI) for TECFIDERA compared to placebo was 0.60 (0.46−0.79; p=0.0002).
`“Data continue to demonstrate that TECFIDERA reduces disability and relapse activity early in the disease course – meaning
`that it can help slow the progression of this debilitating disease, which is particularly important in newly-diagnosed or early
`disease course patients,” said Gilmore O’Neill, M.D., vice president of Multiple Sclerosis Research and Development at
`Biogen. “With more than six years of clinical data supporting its strong, sustained efficacy and well-established safety
`profile, TECFIDERA has been used by more than 170,000 patients worldwide,2 making it the most-prescribed oral MS
`medication globally.”
`Sustained Long-Term Efficacy and Well-Characterized Safety
`Updated six-year data from an integrated post-hoc analysis of the Phase 3 DEFINE, CONFIRM and ENDORSE studies show
`long-term treatment with TECFIDERA resulted in strong and sustained effects on relapses and disability progression in
`newly-diagnosed patients (defined as those patients diagnosed with MS within one year prior to enrolling in DEFINE or
`CONFIRM and either treatment-naïve or previously treated with corticosteroids alone).
`Throughout six years of study (two years in DEFINE or CONFIRM followed by four years in ENDORSE), the ARR for patients who
`started TECFIDERA treatment at the beginning of the study (n=85) remained low at 0.14 (0.10–0.19). In those patients who
`switched from placebo to TECFIDERA, the ARR was substantially reduced from 0.26 (0.18–0.37) from the placebo period
`(years zero to two) to 0.10 (0.06–0.16) when TECFIDERA treatment was received (years three to six), representing a 61
`percent reduction of risk.
`The proportion of patients with 24-week confirmed disability after six years of TECFIDERA treatment was 15.7 percent
`compared to 24.3 percent in those who switched to TECFIDERA treatment in year three. This represents a 49 percent
`reduction of disability risk (p=0.0397) at year six for those who started TECFIDERA treatment from the beginning, compared
`to those who started treatment later after two years of placebo.
`Additional results from the ENDORSE extension study indicate that the favorable overall benefit-risk profile of TECFIDERA has
`remained consistent across all patients who received the therapy, including in those patients treated for up to eight years.
`Data presentation details:
`Efficacy of Delayed-Release Dimethyl Fumarate in Early Multiple Sclerosis: Post-Hoc Analysis of the Phase 3 DEFINE and
`CONFIRM Studies According to Baseline Disability – Poster P565 – Thursday, 8 October – 15:45-17:00 CEST
`Longer-Term Follow-Up of the Efficacy of Delayed-Release Dimethyl Fumarate in Newly Diagnosed Patients with RRMS:
`An Integrated Analysis of DEFINE, CONFIRM, and ENDORSE – Poster P564 – Thursday, 8 October – 15:45-17:00 CEST
`Long-Term Follow-Up of the Safety of Delayed-Release Dimethyl Fumarate in RRMS: Interim Results from the ENDORSE
`Extension Study – Poster P544 – Thursday, 8 October – 15:45-17:00 CEST
`Efficacy of Delayed-Release Dimethyl Fumarate Versus Glatiramer Acetate on a Novel Composite Outcome Measure of
`Inflammatory Disease Activity: Post-Hoc Analysis of the CONFIRM Study – Poster P1063 – Friday, 9 October – 15:30-
`17:00 CEST
`About ENDORSE
`ENDORSE is an ongoing global, dose-blind, Phase 3 extension study to determine the long-term safety and efficacy of
`TECFIDERA (240 mg, BID or TID). The study has enrolled 1,738 patients with RRMS who completed the DEFINE or CONFIRM
`studies. Patients who received two years of TECFIDERA in DEFINE and CONFIRM continued on the same dose (BID or TID) in
`ENDORSE. Patients who previously received placebo or GA (CONFIRM only) were randomized 1:1 to TECFIDERA BID or TID.
`Following TECFIDERA approval at a dose of 240 mg BID, all subjects continuing in this study received open-label TECFIDERA
`240 mg BID. Patients participating in ENDORSE will be followed for up to eight years.
`The primary objective of the study is to evaluate the long-term safety profile of TECFIDERA. Secondary objectives include:
`long-term efficacy of TECFIDERA on clinical outcomes and MS brain lesions on MRI scans; and effects of TECFIDERA on quality
`of life measurements.
`About DEFINE and CONFIRM
`DEFINE (Determination of the Efficacy and safety of oral Fumarate IN relapsing-rEmitting MS) was a global, two-year,
`randomized, multi-center, double-blind, placebo-controlled, dose-comparison Phase 3 clinical trial that enrolled more than
`1,200 patients with RRMS at 198 sites in 28 countries. The study evaluated TECFIDERA (240 mg, BID or TID) compared to
`placebo.
`The primary objective was to determine if TECFIDERA was effective in reducing the proportion of relapsing patients at two
`years. Secondary endpoints included reduction in: the number of new or newly enlarging T2-hyperintense lesions and Gd+
`lesions as measured by MRI; ARR; and disability progression as measured by EDSS. Safety and tolerability of TECFIDERA were
`also assessed.
`CONFIRM (COmparator and aN oral Fumarate In Relapsing-remitting MS) was a global, two-year, randomized, multi-center,
`placebo-controlled, double-blind, dose-comparison Phase 3 clinical trial that enrolled more than 1,400 patients with RRMS at
`200 sites in 28 countries. The study investigated TECFIDERA (240 mg, BID or TID) compared to placebo and included a
`reference comparator arm of glatiramer acetate (GA; 20 mg subcutaneous daily injection) versus placebo.
`The primary objective was to determine whether TECFIDERA was effective in reducing the rate of clinical relapse at two years
`compared to the placebo group. Secondary endpoints at two years included reduction in: the number of new or newly
`enlarging T2-hyperintense lesions and the number of new non-enhancing T1-hypointense lesions (MRI scans were obtained at
`a cohort of sites); the proportion of patients who relapsed; and progression of disability as measured by EDSS. Safety and
`tolerability of TECFIDERA were also assessed.
`About TECFIDERA®
`TECFIDERA is an oral therapy for relapsing forms of MS, including relapsing-remitting MS, the most common form of MS.
`TECFIDERA is currently approved in the United States, the European Union, Canada, Australia and Switzerland. Through a
`robust clinical trial program and commercial launches starting with the United States in March 2013, more than 170,000
`patients have been treated with TECFIDERA worldwide.2
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`TECFIDERA has been proven to reduce rate of MS relapses, slow the progression of disability, and the number of MS brain
`lesions, while demonstrating a favorable benefit-risk profile in a broad range of patients with relapsing forms of MS. 3 In
`clinical trials, the most common adverse events associated with TECFIDERA were flushing and gastrointestinal (GI) events.
`Other side effects included a decrease in mean lymphocyte counts during the first year of treatment, which then plateaued.
`TECFIDERA is contraindicated in patients with a known hypersensitivity to dimethyl fumarate or any of the excipients of
`TECFIDERA. Rare cases of progressive multifocal leukoencephalopathy (PML) have been seen with TECFIDERA patients in the
`setting of severe and prolonged lymphopenia.
`The efficacy and safety of TECFIDERA have been studied in a large, global clinical program, which includes an ongoing long-
`term extension study. It is believed that TECFIDERA provides a new approach to treating MS by activating the Nrf2 pathway,
`although its exact mechanism of action is unknown. This pathway provides a way for cells in the body to defend themselves
`against inflammation and oxidative stress caused by conditions like MS.
`For additional important safety information, and the United States full prescribing information, please visit
`www.tecfidera.com [4].
`About Biogen
`Through cutting-edge science and medicine, Biogen discovers, develops and delivers to patients worldwide innovative
`therapies for the treatment of neurodegenerative diseases, hematologic conditions and autoimmune disorders. Founded in
`1978, Biogen is one of the world’s oldest independent biotechnology companies and patients worldwide benefit from its
`leading multiple sclerosis and innovative hemophilia therapies. For product labeling, press releases and additional information
`about the company, please visit http://www.biogen.com [5].
`Safe Harbor
`This press release includes forward-looking statements, including statements about the potential benefits of TECFIDERA in
`newly diagnosed and early onset MS patients. These forward-looking statements may be accompanied by such words as
`"anticipate," "believe," "estimate," "expect," "forecast," "intend," "may," "plan," "will," and other words and terms of similar
`meaning. You should not place undue reliance on these statements. 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.
`Factors which could cause actual results to differ materially from our current expectations include the risk that unexpected
`concerns may arise from additional data or analysis, regulatory authorities may require additional information or further
`studies, or may fail to approve or may delay approval of our drug candidates, or we may encounter other unexpected
`hurdles. For more detailed information on the risks and uncertainties associated with our drug development and
`commercialization activities, please review the Risk Factors section of our most recent annual or quarterly report filed with
`the Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak
`only as of the date of this press release. We do not undertake any obligation to publicly update any forward-looking
`statements.
`1 Glatiramer acetate was an active reference comparator
`2 Combined post-marketing and clinical trials exposure to TECFIDERA as of August 31, 2015
`3 TECFIDERA is approved in the European Union for relapsing-remitting multiple sclerosis
`
`Language:
`English
`Contact:
`Biogen
`MEDIA CONTACT:
`Catherine Falcetti, +1 781-464-3260
`public.affairs@biogen.com [6]
`or
`INVESTOR CONTACT:
`Carlo Tanzi, Ph.D., +1 781-464-2442
`IR@biogen.com [7]
`Ticker Slug:
`Ticker:BIIB
`Exchange:NASDAQ
`ISIN:
`US09062X1037
`
`Source URL: http://media.biogen.com/press-release/neurology/new-data-show-strong-sustained-effects-tecfidera-dimethyl-
`fumarate-newly-dia
`Links:
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`[2] http://www.businesswire.com
`[3] http://cts.businesswire.com/ct/CT?
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