Biogen Announces Topline Results from the Tofersen Phase 3
Study and its Open-Label Extension in SOD1-ALS
Biogen Inc. (Nasdaq: BIIB) today announced topline results from its
pivotal Phase 3 VALOR study of tofersen (BIIB067), an
investigational antisense drug being evaluated for people with
superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS).
While tofersen did not meet the primary endpoint of change from
baseline to week 28 in the Revised Amyotrophic Lateral Sclerosis
Functional Rating Scale (ALSFRS-R), trends favoring tofersen were
seen across multiple secondary and exploratory measures of biologic
activity and clinical function.
In addition, a pre-specified integration of data from VALOR and
its ongoing open-label extension study (OLE) reinforced these
findings and showed that early tofersen initiation led to less
decline across multiple measures of motor function, respiratory
function, muscle strength, and quality of life in people with
SOD1-ALS. Most adverse events in both VALOR and OLE were mild to
moderate in severity, including procedural pain, headache, pain in
extremity, fall and back pain.
Biogen is actively engaging with regulators, the medical
community, patient advocacy groups and other key stakeholders
around the world to determine potential next steps.
“The results from the VALOR study are encouraging as they show
reduction of SOD1 protein, reduction of neurofilament, a potential
biomarker for neurodegenerative disease, and positive signals
across multiple key endpoints including measures of important
aspects of the daily lives of SOD1-ALS patients,” said Timothy
Miller, M.D., Ph.D., principal investigator of VALOR and ALS Center
Director at Washington University School of Medicine, St. Louis.
“The wait for new options has been long and difficult for the ALS
community, and we welcome this important research advancement in
this difficult to treat disease space.”
“Data from the tofersen Phase 3 study and its open-label
extension showed signs of slowing disease progression in people
with SOD1-ALS, a rare, devastating disease that leads to loss of
everyday functions and ultimately death,” said Alfred Sandrock,
Jr., M.D., Ph.D., Head of Research and Development at Biogen.
“Following discussions with investigators, bioethicists, and having
listened to the voice of patient advocacy groups, we will broaden
early access to tofersen to all eligible SOD1-ALS patients through
our already established expanded access program. We are grateful
for the courageous efforts of patients, families, advocates, and
the scientific community who have contributed to this important
research.”
ALS is a progressive neurodegenerative disease that is uniformly
fatal with an average survival of three to five years. The most
common cause of death is respiratory failure. SOD1-ALS is a rare,
genetic form of ALS that accounts for approximately two percent of
the estimated 168,000 people who have the disease globally.
Currently, there are no genetically targeted treatment options for
ALS.
Click here for a fact sheet to learn more about genetic
amyotrophic lateral sclerosis
(ALS):http://ml.globenewswire.com/Resource/Download/ae9c9142-ae2a-4d95-8f6f-0b5cf6e80963
In light of the critical unmet need, Biogen will expand
eligibility for its ongoing early access program (EAP) to all
people with SOD1-ALS, in countries where such programs are
permitted by local regulations and future access may be secured.
EAP programs enable patients to gain access to a medicine free of
charge before the treatment is licensed commercially. If a clear
path forward for tofersen is not established, or if another
controlled trial is required by regulators, Biogen may revise or
discontinue the EAP.
The VALOR and Open-Label Extension Studies
VALOR was a 28-week Phase 3, randomized, double-blind,
placebo-controlled study to evaluate the efficacy, safety and
tolerability, pharmacodynamic, and biomarker 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). Sixty of these participants met the
study’s protocol-defined enrichment criteria for rapid disease
progression, comprising the primary analysis population (“faster
progressing”). Forty-eight participants did not meet these
prognostic enrichment criteria (“slower progressing”).
The open-label extension study is an ongoing Phase 3 study for
participants who completed VALOR. Of the 108 participants in VALOR,
95 enrolled in the OLE.
Topline Results
In VALOR the primary efficacy endpoint of change from baseline
to week 28 in the Revised Amyotrophic Lateral Sclerosis Functional
Rating Scale (ALSFRS-R) total score in the primary analysis
(faster-progressing) population did not reach statistical
significance as measured by a joint-rank analysis (difference of
1.2; p=0.97).
Trends favoring tofersen were seen across multiple secondary and
exploratory measures of biologic activity and clinical function,
including motor function, respiratory function, and quality of
life. On the first key secondary endpoint of change from baseline
in total CSF SOD1 protein, a marker of target engagement,
differences were observed between the tofersen and placebo groups
of 38% and 26% in the faster- and slower-progressing populations,
respectively. On the second key secondary endpoint of change from
baseline in plasma neurofilament light chain (NfL), a potential
marker of neuronal degeneration, differences were observed between
the tofersen and placebo groups of 67% and 48% in the faster- and
slower-progressing populations, respectively.
In the faster-progressing population, trends favored tofersen on
measures of respiratory function (Slow Vital Capacity (SVC);
difference of 7.9 percent-predicted) and muscle strength (Hand-held
dynamometer (HHD); difference of 0.02). Similar trends were
observed across multiple exploratory patient-reported outcome
measures of disease severity, quality of life, and fatigue. Median
time to event could not be estimated for survival analyses due to
the low number of events over the 28-week period.
In addition, with longer-term follow up in the OLE, earlier
tofersen initiation consistently led to a reduction in decline in
measures of clinical function across the population.
The most common adverse events (AEs) in participants receiving
tofersen in the VALOR study were procedural pain, headache, pain in
extremity, fall and back pain. Most AEs in both VALOR and the OLE
were mild to moderate in severity. In VALOR, serious AEs were
reported in 18.1% of participants receiving tofersen and 13.9% of
those receiving placebo. In the tofersen group, 5.6% of
participants discontinued treatment due to an AE. There were no
discontinuations due to AEs in the placebo group. Serious
neurologic events were reported in 4.8% of patients receiving
tofersen in VALOR and its OLE, including 2 cases of myelitis
(2.0%). There was one death reported in the tofersen-treated group
in VALOR, which was determined not to be related to tofersen.
American Neurological Association (ANA) Annual Meeting
Presentation Details
Results from VALOR and the OLE are being presented at the ANA
Annual Meeting.
Sunday, October 17, 2021, 4:20 p.m. ET – Results from the Phase
3 VALOR study and its open-label extension: evaluating the clinical
efficacy and safety of tofersen in adults with ALS and confirmed
SOD1 mutation, presented by Timothy Miller, M.D., Ph.D., principal
investigator of VALOR and ALS Center Director at Washington
University School of Medicine, St. Louis.
To access the presentation, please go to the Investors section
of Biogen’s website at investors.biogen.com. Following the event,
an archived version will be available on the website.
Biogen’s Commitment to ALSFor over a decade,
Biogen has been committed to advancing ALS research to provide a
deeper understanding 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 broad 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 broad pipeline of
investigational drugs being evaluated in ALS.
About TofersenTofersen is an antisense drug
being evaluated for the potential treatment of SOD1-ALS. Tofersen
binds to SOD1 mRNA, allowing for its degradation by RNase-H in an
effort to reduce synthesis of SOD1 protein production. Tofersen is
also being studied in the Phase 3 ATLAS study, which is designed to
evaluate the ability of tofersen to 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 the Phase 3 VALOR Study (NCT02623699)
VALOR was a Phase 3, randomized, double-blind,
placebo-controlled study to evaluate the efficacy, safety,
tolerability and pharmacodynamic effects of tofersen 100 mg in
adults with ALS and a confirmed SOD1 mutation. Subjects were
randomized to receive tofersen or placebo. In total, 108
participants were randomized in VALOR (n=72 to tofersen 100 mg and
n=36 to placebo). Sixty of these participants met the study’s
prognostic enrichment criteria for rapid disease progression based
on SOD1 mutation type and pre-randomization ALSFRS-R slope decline
and comprised the primary analysis population (“faster-progressing
population”). Forty-eight participants did not meet these
prognostic enrichment criteria (“slower-progressing population”).
For more information about the Phase 3 VALOR study, visit
www.clinicaltrials.gov.
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. Life expectancy for people with ALS is 3-5
years from time of symptom onset. Multiple genes have been
implicated in ALS. Mutations in the SOD1 gene are responsible for
approximately two percent of all ALS cases (SOD1-ALS). SOD1-ALS can
occur in patients with or without a family history of ALS. Genetic
testing may help determine if a person’s ALS is associated with a
genetic mutation, even in individuals without a family history of
the disease.
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. 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, neuropsychiatry,
immunology, acute neurology and neuropathic pain.
We routinely post information that may be important to investors
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Biogen Safe Harbor StatementThis 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; the potential clinical
effects of tofersen; the potential benefits, safety and efficacy of
tofersen; the clinical development program for 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
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“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
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