-- Diroximel Fumarate Demonstrated Statistically Superior
Gastrointestinal (GI) Tolerability on EVOLVE-MS-2 Study's Primary
Endpoint Assessing Self-Reported GI Events --
-- Discontinuations Due to GI Events were Less than 1% for
Diroximel Fumarate --
DUBLIN and CAMBRIDGE, Massachusetts, July 30, 2019 /PRNewswire/ -- Alkermes plc
(Nasdaq: ALKS) and Biogen Inc. (Nasdaq: BIIB) today announced
positive topline results from EVOLVE-MS-2, a large, randomized,
double-blind, five-week, Phase 3 study of diroximel fumarate, an
investigational, novel oral fumarate with a distinct chemical
structure, for relapsing-remitting multiple sclerosis (RRMS),
compared to TECFIDERA® (dimethyl fumarate). Diroximel
fumarate was statistically superior to dimethyl fumarate on the
study's pre-specified primary endpoint, with patients treated with
diroximel fumarate self-reporting significantly fewer days of key
gastrointestinal (GI) symptoms with intensity scores ≥2 on the
Individual Gastrointestinal Symptom and Impact Scale (IGISIS), as
compared to dimethyl fumarate (p = 0.0003).
The most common adverse events (AEs) reported in the study for
both treatment groups were flushing, diarrhea and nausea (32.8%,
15.4% and 14.6% for diroximel fumarate; 40.6%, 22.3% and 20.7% for
dimethyl fumarate). The overall proportion of patients with AEs
leading to study discontinuation were 1.6% for diroximel fumarate
and 6.0% for dimethyl fumarate. Of those, the proportion of
patients who discontinued due to GI adverse events during the
five-week treatment period were 0.8% for diroximel fumarate and
4.8% for dimethyl fumarate. Further analysis of the data from the
EVOLVE-MS-2 study is ongoing and will be presented at a future
scientific forum.
"As part of our leadership in multiple sclerosis, Biogen has
long understood that the disease differs from person to person, as
well as throughout the course of the disease. We are committed to
offering a range of options to patients to meet their needs," said
Michael Ehlers, executive vice
president, research & development at Biogen. "These data build
on the foundation we have created with TECFIDERA, the most
prescribed oral MS therapy worldwide, and further demonstrate the
potential of diroximel fumarate as a novel oral fumarate within our
MS portfolio."
"Diroximel fumarate demonstrated statistically superior GI
tolerability compared to dimethyl fumarate on the EVOLVE-MS-2
study's primary endpoint, as well as a low discontinuation rate of
less than 1% due to GI adverse events. These results reinforce the
safety and tolerability profile diroximel fumarate has consistently
demonstrated across the EVOLVE-MS development program, underscoring
the potential importance of diroximel fumarate for the treatment of
people living with relapsing-remitting MS. We look forward to the
FDA's completion of its review of the diroximel fumarate NDA in the
fourth quarter," said Craig
Hopkinson, M.D., chief medical officer and senior vice
president of medicines development and medical affairs at
Alkermes.
EVOLVE-MS-2 was a Phase 3, multicenter, double-blind,
active-controlled, five-week study designed to evaluate the GI
tolerability, including duration and severity, of diroximel
fumarate 462 mg twice daily compared to dimethyl fumarate 240 mg
twice daily in 506 patients with RRMS. The study's primary endpoint
assessed the number of days patients reported GI symptoms with a
symptom intensity score ≥2 on the IGISIS rating scale spanning 0
(not at all) through 10 (extreme). The IGISIS was completed twice
daily and evaluated the intensity of key GI symptoms, including
nausea, vomiting, upper and lower abdominal pain, and diarrhea.
"With a chronic disease like MS, interrupting or stopping
treatment due to GI side effects can often provoke the return of
disease activity. Physicians and patients should work together to
choose a medication that provides the right balance of efficacy,
safety and tolerability to help manage patients' MS and meet their
treatment goals," said Robert
Naismith, M.D., professor of neurology, Washington University School of Medicine in
St. Louis. "These topline results
suggest that diroximel fumarate offers a differentiated GI
tolerability profile and may represent an important new option for
people living with relapsing MS."
The EVOLVE-MS-2 study is part of the EVOLVE-MS diroximel
fumarate clinical development program, which is being conducted as
part of a worldwide development and commercialization agreement
between Alkermes and Biogen. Diroximel fumarate is currently under
review with the U.S. Food and Drug Administration (FDA) with a
PDUFA (Prescription Drug User Fee Act) target action date in the
fourth quarter of 2019. Biogen intends to market diroximel fumarate
under the conditionally approved brand name
VUMERITY™.
About Diroximel Fumarate
Diroximel fumarate is an
investigational, novel oral fumarate candidate with a distinct
chemical structure 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 TECFIDERA® (dimethyl fumarate) as part of
the 505(b)(2) regulatory pathway. Diroximel fumarate is currently
under review with the U.S. Food and Drug Administration (FDA) with
a PDUFA (Prescription Drug User Fee Act) target action date in the
fourth quarter of 2019. If approved by the FDA, Biogen intends to
market diroximel fumarate under the conditionally approved brand
name VUMERITY™.
About the Diroximel Fumarate EVOLVE-MS Clinical Development
Program
The key components of the EVOLVE-MS
(Endeavoring to Advance Treatment for Patients
Living with Multiple Sclerosis) clinical
development program of diroximel fumarate include the EVOLVE-MS-1
study, a Phase 3, open-label, two-year safety study in
relapsing-remitting MS patients, along with pharmacokinetic
bridging studies comparing diroximel fumarate and dimethyl fumarate
to demonstrate bioequivalence. The EVOLVE-MS clinical
development program also includes EVOLVE-MS-2, a Phase 3, five-week
randomized, prospective, double-blind, multi-center study assessing
the GI tolerability of diroximel fumarate and dimethyl
fumarate.
About Tecfidera® (dimethyl fumarate)
TECFIDERA is the most prescribed oral medication for relapsing
multiple sclerosis (MS) in the world and has been shown to reduce
the rate of MS relapses, slow the progression of disability and
impact the number of MS brain lesions, while demonstrating a
well-characterized safety profile in people with relapsing forms of
MS. TECFIDERA is approved in 69 countries and more than
398,000 patients have been treated with it, representing more than
740,000 patient-years of exposure across clinical trial use and
patients prescribed TECFIDERA. Of these, 6,335 patients (12,985
patient-years) were from clinical trials.[i] TECFIDERA
is indicated in the U.S. for the treatment of patients with
relapsing forms of MS, to include clinically isolated syndrome,
relapsing-remitting disease, and active secondary progressive
disease, in adults. TECFIDERA is approved in the European Union for
relapsing-remitting MS.
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, a rare opportunistic viral infection of the
brain which has been associated with death or severe disability,
have been seen with TECFIDERA patients in the setting of prolonged
lymphopenia although the role of lymphopenia in these cases is
uncertain. Other serious side effects include a decrease in mean
lymphocyte counts during the first year of treatment, which then
plateaued, and liver function abnormalities, which resolved upon
treatment discontinuation. In clinical trials, the most common
adverse events associated with TECFIDERA were flushing and
gastrointestinal (GI) events.
Please click here for Important Safety
Information and full Prescribing Information,
including Patient Information for TECFIDERA in the U.S.,
or visit your respective country's product website.
About Alkermes plc
Alkermes plc is a fully
integrated, global biopharmaceutical company developing innovative
medicines for the treatment of central nervous system (CNS)
diseases and oncology. The company has a diversified commercial
product portfolio and a substantial clinical pipeline of product
candidates for chronic diseases that include schizophrenia,
depression, addiction, multiple sclerosis and cancer. Headquartered
in Dublin, Ireland, Alkermes plc
has an R&D center in Waltham,
Massachusetts; a research and manufacturing facility in
Athlone, Ireland; and a
manufacturing facility in Wilmington,
Ohio. For more information, please visit Alkermes' website
at www.alkermes.com.
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 neuroscience 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.
Alkermes Note Regarding Forward-Looking
Statements
Certain statements set forth in this press
release constitute "forward-looking statements" within the meaning
of the Private Securities Litigation Reform Act of 1995, as
amended, including, but not limited to, statements concerning: the
continued clinical development and the potential therapeutic and
commercial value of diroximel fumarate for the treatment of
relapsing forms of MS; plans for presentation of the EVOLVE-MS-2
data at an upcoming scientific forum; the timing and potential
outcome of the FDA review of the NDA for diroximel fumarate; the
differentiated GI tolerability profile of diroximel fumarate in the
future treatment of patients with relapsing forms of MS; and the
potential financial, commercial and therapeutic benefits that may
be achieved through collaboration with Biogen under the license and
collaboration agreement between Alkermes and Biogen. Alkermes
cautions that forward-looking statements are inherently uncertain.
Although Alkermes believes that such statements are based on
reasonable assumptions within the bounds of its knowledge of its
business and operations, the forward-looking statements are neither
promises nor guarantees and they are necessarily subject to a high
degree of uncertainty and risk. Actual performance and results may
differ materially from those expressed or implied in the
forward-looking statements due to various risks and uncertainties.
These risks and uncertainties include, among others: whether
preclinical and early clinical results for diroximel fumarate will
be predictive of future clinical study results or real-world
results; whether clinical trials for diroximel fumarate will be
completed on time or at all; whether diroximel fumarate could be
shown ineffective or unsafe during clinical studies, and whether,
in such instances, Alkermes or Biogen may not be permitted by
regulatory authorities to undertake new or additional clinical
studies of diroximel fumarate; whether regulatory submissions for
diroximel fumarate will be submitted on time or at all; whether
adverse decisions by regulatory authorities will occur; whether the
data included in the NDA for diroximel fumarate will meet the FDA's
requirements for approval; whether the potential financial,
commercial and therapeutic benefits of collaboration with Biogen
under the license and collaboration agreement between Alkermes and
Biogen will be achieved; and those risks described in the Alkermes
Annual Report on Form 10-K for the year ended Dec. 31, 2018 and in subsequent filings made by
Alkermes with the U.S. Securities and Exchange Commission (SEC),
which are available on the SEC's website at www.sec.gov. Existing
and prospective investors are cautioned not to place undue reliance
on these forward-looking statements, which speak only as of the
date hereof. Except as required by law, Alkermes disclaims any
intention or responsibility for updating or revising any
forward-looking statements contained in this press release.
Biogen Safe Harbor
This press 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 diroximel fumarate; potential clinical effects of
diroximel fumarate; results from the EVOLVE-MS-2 study; the
clinical development program for diroximel fumarate; potential
regulatory approval and the timing thereof; clinical trial results
and plans; Biogen's research and development program for the
treatment of MS; the treatment of MS; the potential of Biogen's
commercial business and pipeline programs, including diroximel
fumarate; the anticipated benefits and potential of Biogen's
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
Biogen's drug candidates, including diroximel fumarate; actual
timing and content of submissions to and decisions made by the
regulatory authorities regarding Biogen's drug candidates,
including diroximel fumarate; 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 diroximel fumarate; unexpected concerns
may arise from additional data, analysis or results obtained during
clinical trials; failure to protect and enforce Biogen's 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 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 Biogen 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
press 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.
TECFIDERA® is a registered trademark
of Biogen Inc.; VUMERITY™ is a trademark of Alkermes Pharma
Ireland Limited used by Biogen under an exclusive license.
[i] Combined post-marketing data based on
prescriptions and clinical trials exposure to TECFIDERA as of
April 30, 2019.
Alkermes Contacts:
For Investors: Sandy Coombs +1 781
609 6377
For Media: Gretchen Murphy +1 781
609 6419
Biogen Contacts:
For Investors: Joe Mara, +1 781 464
2442, IR@biogen.com
For Media: David Caouette, + 617 679
4945, public.affairs@biogen.com
Logo -
https://mma.prnewswire.com/media/616416/Alkermes_plc_Logo.jpg
Logo -
https://mma.prnewswire.com/media/799041/Biogen__Logo.jpg