CARLSBAD, Calif., Oct. 17, 2021 /PRNewswire/ -- Ionis
Pharmaceuticals, Inc. (NASDAQ: IONS) partner Biogen today announced
topline results from its placebo-controlled pivotal Phase 3 VALOR
study of tofersen (BIIB067), an investigational antisense medicine
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 disease 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 including 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, which licensed tofersen from Ionis in 2018, also
announced today that it is actively engaging with regulators, the
medical community, patient advocacy groups and other key
stakeholders around the world to determine next steps.
"The topline results of the Phase 3 VALOR study showed signs of
reduced disease progression across key secondary and exploratory
endpoints, including biomarker data, clinical outcomes and quality
of life measures. These data represent an important step forward in
our commitment to find new treatments for this devastating disease.
We applaud the efforts of Biogen, whose advancement of tofersen
reflects the promise of our broad partnership to develop medicines
for the treatment of neurological diseases," said Brett P. Monia, Ph.D., chief executive officer
of Ionis.
"Given Ionis' long-standing commitment to the ALS community, we
are encouraged by the results of the Phase 3 VALOR study of
tofersen and its open-label extension, which showed signs of
slowing disease progression in people living with SOD1-ALS," said
C. Frank Bennett, Ph.D., Ionis'
executive vice president, chief scientific officer and franchise
leader for neurological programs. "On behalf of all of us at Ionis,
I would like to express our deep gratitude to the patients,
families, scientific investigators, and others who participated in
the VALOR study."
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.
In light of the critical unmet need, Biogen announced that it
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 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:
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 at
https://investors.biogen.com/
About Tofersen
Tofersen is an antisense medicine being evaluated for the
potential treatment of SOD1-ALS. Tofersen binds to SOD1 mRNA,
allowing for its degradation by RNase-H1 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 Ionis' Neurology Franchise
The Ionis neurology franchise addresses all major brain regions
and central nervous system cell types and currently has four Phase
3 studies ongoing with 11 medicines in clinical development, three
of which are wholly owned. Ionis is leading the way in treating
root causes of many neurological diseases and developing antisense
medicines for common diseases like Alzheimer's and Parkinson's as
well as rare diseases like amyotrophic lateral sclerosis (ALS) and
Alexander disease. Ionis' marketed neurological disease medicines
include SPINRAZA®, a global foundation of care for
spinal muscular atrophy (SMA), licensed to and commercialized by
Biogen.
About Ionis Pharmaceuticals
For more than 30 years, Ionis has been the leader in
RNA-targeted therapy, pioneering new markets and changing standards
of care with its novel antisense technology. Ionis currently has
three marketed medicines and a premier late-stage pipeline
highlighted by industry leading neurological and cardiometabolic
franchises. Our scientific innovation began and continues with the
knowledge that sick people depend on us, which fuels our vision of
becoming one of the most successful biotechnology companies.
To learn more about Ionis visit www.ionispharma.com and follow
us on twitter @ionispharma.
Ionis' Forward-looking Statement
This press release includes forward-looking statements regarding
Ionis' business and the therapeutic and commercial potential of
Ionis' technologies, tofersen and other products in
development. Any statement describing Ionis' goals, expectations,
financial or other projections, intentions or beliefs is a
forward-looking statement and should be considered an at-risk
statement. Such statements are subject to certain risks and
uncertainties, including those related to the impact COVID-19 could
have on our business, and including but not limited to those
related to our commercial products and the medicines in our
pipeline, and particularly those inherent in the process of
discovering, developing and commercializing medicines that are safe
and effective for use as human therapeutics, and in the endeavor of
building a business around such medicines. Ionis' forward-looking
statements also involve assumptions that, if they never materialize
or prove correct, could cause its results to differ materially from
those expressed or implied by such forward-looking statements.
Although Ionis' forward-looking statements reflect the good
faith judgment of its management, these statements are based only
on facts and factors currently known by Ionis. As a result, you are
cautioned not to rely on these forward-looking statements. These
and other risks concerning Ionis' programs are described in
additional detail in Ionis' annual report on Form 10-K for the year
ended December 31, 2020, and the most
recent Form 10-Q quarterly filing, which are on file with the SEC.
Copies of these and other documents are available from the
Company.
In this press release, unless the context requires otherwise,
"Ionis," "Company," "we," "our," and "us" refers to Ionis
Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals® is a trademark of Ionis
Pharmaceuticals, Inc.
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SOURCE Ionis Pharmaceuticals, Inc.