The New England Journal of Medicine Publishes Pivotal Tofersen Data
that Show Benefits in Rare, Genetic Form of ALS
Biogen Inc. (Nasdaq: BIIB) today announced that The New England
Journal of Medicine (NEJM) has published detailed results from
the Phase 3 VALOR study and the combined analysis of VALOR and its
open label extension (OLE) study evaluating tofersen for the
treatment of superoxide dismutase 1 (SOD1) amyotrophic lateral
sclerosis (ALS). There is currently no treatment targeted for
SOD1-ALS.
“I see three key take home points from these data. First,
tofersen clearly leads to lowering of SOD1 protein, as would be
expected. Second there is substantial lowering of
neurofilament levels, which I interpret as potentially slowing the
underlying disease process. And third, there is a meaningful
clinical benefit when looking at the later time points in the open
label extension,” said Timothy Miller, M.D., Ph.D., principal
investigator of VALOR and ALS Center co-Director at Washington
University School of Medicine, St. Louis. “We are grateful to the
dedication from participants, their families, and the sites for
taking part in this important study.”
Data from the combined analysis were previously presented at the
European Network to Cure ALS (ENCALS) annual meeting and included
within Biogen’s New Drug Application for tofersen that was recently
accepted for priority review by the U.S. Food and Drug
Administration. The application was given a Prescription Drug User
Fee Act action date of January 25, 2023.
“The ALS community has been actively pursuing new medicines for
decades. To have data like these published in NEJM gives us energy
and hope. We are now seeing in the data what we suspected about
tofersen for a long time – that it has the potential to make a
clinical difference for people living with SOD1-ALS,” said Merit
Cudkowicz, M.D., co-principal investigator of the VALOR trial and
co-founder of the Northeast ALS Consortium, Director of the Healey
& AMG Center for ALS and Chair of Neurology at Massachusetts
General Hospital and the Julieanne Dorn Professor of Neurology at
Harvard Medical School. “The lowering of neurofilament, a marker of
axonal injury and neurodegeneration along with the clinical data,
highlights the potential of tofersen.”
About VALOR and the OLEVALOR was a six-month
Phase 3, randomized, double-blind, placebo-controlled study to
evaluate the effects of tofersen 100 mg in adults with ALS
associated with a SOD1 mutation. In total, 108 participants were
randomized in VALOR (n=72 to tofersen 100 mg and n=36 to placebo).
Of these participants, 95 enrolled in the ongoing OLE. At the time
of the analysis all participants had an opportunity for at least 12
months of follow-up, with a median exposure to tofersen of
approximately 20 months (range: 1 – 34 months).
The primary endpoint of VALOR was change from baseline to week
28 in ALS Functional Rating Scale-Revised (ALSFRS-R) total score.
Secondary endpoints included changes in total cerebrospinal fluid
SOD1 protein concentration, plasma neurofilament light chain (NfL),
slow vital capacity and handheld dynamometry in 16 muscles.
As previously reported in October 2021, VALOR did not meet the
primary endpoint. However, trends of reduced disease progression
across multiple secondary and exploratory endpoints were observed.
The combined VALOR and OLE 12-month data, in which the clinical
analyses adjusted for neurofilament levels as a marker of the
disease progression rate at baseline, showed sustained reductions
in SOD1 protein (a marker of target engagement) and neurofilament
(a marker of neurodegeneration) and slowed decline in clinical
function, respiratory function, strength, and quality of life with
earlier initiation of tofersen.
In the 12-month data, the most common adverse events (AEs) in
participants receiving tofersen in VALOR and the OLE study were
procedural pain, headache, pain in the arms or legs, falls, and
back pain. Most AEs in both VALOR and the OLE were mild to moderate
in severity. Serious neurologic events including myelitis, chemical
or aseptic meningitis, radiculitis, increased intracranial pressure
and papilledema, were reported in 6.7 percent of participants
receiving tofersen in VALOR and its OLE.
About TofersenTofersen is an antisense drug
being evaluated for the potential treatment of SOD1-ALS. Tofersen
binds and degrades SOD1 mRNA to reduce synthesis of SOD1 protein
production. In addition to the ongoing open label extension of
VALOR, tofersen is being studied in the Phase 3 ATLAS study
designed to evaluate whether tofersen can delay clinical onset when
initiated in presymptomatic individuals with a SOD1 genetic
mutation and biomarker evidence of disease activity. Biogen
licensed tofersen from Ionis Pharmaceuticals, Inc. under a
collaborative development and license agreement.
About Amyotrophic Lateral Sclerosis and
SOD1-ALSAmyotrophic lateral sclerosis (ALS) is a rare,
progressive and fatal neurodegenerative disease that results in the
loss of motor neurons in the brain and the spinal cord that are
responsible for controlling voluntary muscle movement. People with
ALS experience muscle weakness and atrophy, causing them to lose
independence as they steadily lose the ability to move, speak, eat,
and eventually breathe. Average life expectancy for people with ALS
is three to five years from time of symptom onset.1
Multiple genes have been implicated in ALS. Genetic testing
helps determine if a person’s ALS is associated with a genetic
mutation, even in individuals without a family history of the
disease. Currently, there are no genetically targeted treatment
options for ALS. Mutations in the SOD1 gene are responsible for
approximately 2 percent of the estimated 168,000 people who have
ALS globally (SOD1-ALS).2 Life expectancy in SOD1-ALS varies
widely with some patients surviving less than a year.3
Biogen’s Continuous Commitment to ALSFor over a
decade, Biogen has been committed to advancing ALS research to
provide a deeper understanding of all forms of the disease. The
company has continued to invest in and pioneer research despite
making the difficult decision to discontinue a late-stage ALS asset
in 2013. Biogen has applied important learnings to its portfolio of
assets for genetic and other forms of ALS, with the goal of
increasing the probability of bringing a potential therapy to
patients in need. These applied learnings include evaluating
genetically validated targets in defined patient populations,
pursuing the most appropriate modality for each target and
employing sensitive clinical endpoints. Today, the company has a
pipeline of investigational drugs being evaluated in ALS, including
tofersen and BIIB105.
About BiogenAs pioneers in neuroscience, Biogen
discovers, develops, and delivers worldwide innovative therapies
for people living with serious neurological 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, Sir Kenneth Murray, and Nobel Prize
winners Walter Gilbert and Phillip Sharp. Today, Biogen has a
leading portfolio of medicines to treat multiple sclerosis, has
introduced the first approved treatment for spinal muscular
atrophy, and developed the first and only approved treatment to
address a defining pathology of Alzheimer’s disease. Biogen is also
commercializing biosimilars and focusing on advancing one of the
industry’s most diversified pipelines in neuroscience that will
transform the standard of care for patients in several areas of
high unmet need.
In 2020, Biogen launched a bold 20-year, $250 million initiative
to address the deeply interrelated issues of climate, health, and
equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil
fuels across the company’s operations, build collaborations with
renowned institutions to advance the science to improve human
health outcomes, and support underserved communities.
We routinely post information that may be important to investors
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Biogen Safe HarborThis news release contains
forward-looking statements, including statements made pursuant to
the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995, including statements about results from the
Phase 3 VALOR study of tofersen or its OLE; the potential clinical
effects of tofersen; the potential benefits, safety and efficacy of
tofersen; the clinical development program for tofersen; the
potential approval of tofersen; the identification and treatment of
ALS; our research and development program for the treatment of ALS;
the potential of our commercial business and pipeline programs,
including tofersen; and risks and uncertainties associated with
drug development and commercialization. These forward-looking
statements may be accompanied by words such as “aim,” “anticipate,”
“believe,” “could,” “estimate,” “expect,” “forecast,” “intend,”
“may,” “plan,” “potential,” “possible,” “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, uncertainty of
success in the development and potential commercialization of
tofersen; 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; regulatory authorities may require additional
information or further studies, or may fail or refuse to approve or
may delay approval of our drug candidates, including tofersen; the
occurrence of adverse safety events; the risks of unexpected
hurdles, 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; product liability claims; 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:
- Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. N Engl J
Med. 2017 Jul 13.
- Brown CA, Lally C, Kupelian V, Flanders WD. Estimated
Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1
and C9orf72 Genetic Variants. Neuroepidemiology. 2021.
- Brown CA, Lally C, Kupelian V, Flanders WD. Estimated
Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1
and C9orf72 Genetic Variants. Neuroepidemiology. 2021.
MEDIA CONTACT:Dan Haro+ 1 617 914
6936public.affairs@biogen.com |
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