- Accelerated approval marks a scientific advancement in
treatment of superoxide dismutase 1 (SOD1)-amyotrophic lateral
sclerosis (ALS)
- Approval based on reduction of neurofilament, a biomarker
associated with neuronal damage in ALS
- QALSODY joins SPINRAZA® as Ionis-discovered
medicine approved for treatment of a rare and fatal
neurodegenerative disease
CARLSBAD, Calif., April 25,
2023 /PRNewswire/ -- Ionis Pharmaceuticals,
Inc. (Nasdaq: IONS) today announced that its partner Biogen
has received U.S. Food and Drug Administration (FDA) approval of
QALSODY™ (tofersen) 100 mg/15mL injection for the treatment of
amyotrophic lateral sclerosis (ALS) in adults who have a mutation
in the superoxide dismutase 1 (SOD1) gene. This indication
is approved under accelerated approval based on a reduction in
plasma neurofilament light chain (NfL) observed in patients treated
with QALSODY. Continued approval for this indication may be
contingent upon verification of clinical benefit from ongoing
trial(s). The ongoing Phase 3 ATLAS study of tofersen in people
with presymptomatic SOD1-ALS will serve as the confirmatory
study. QALSODY is the first and only approved treatment to target a
genetic cause of ALS and the latest Ionis-discovered medicine to
gain market approval.
Neurofilaments are proteins that are released from neurons when
they are damaged, making them a marker of neurodegeneration.
"Today's approval of QALSODY represents a scientific advancement
for the ALS community. We thank the people with SOD1-ALS
whose participation in the clinical studies made this day possible.
We are proud of the Ionis scientists whose dedication made the
discovery of this medicine possible, and we are appreciative of our
partners at Biogen for their ongoing commitment to ALS," said
Brett P. Monia, Ph.D., chief
executive officer of Ionis. "The QALSODY approval highlights our
significant progress advancing RNA-based treatments targeting
severe neurological diseases."
Warnings and precautions associated with QALSODY were serious
neurologic events, including myelitis and or radiculitis;
papilledema and elevated intracranial pressure; and aseptic
meningitis. If symptoms consistent with myelitis, radiculitis
papilledema, elevated intracranial, or aseptic meningitis develop,
diagnostic workup and treatment should be initiated according to
the standard of care. Management may require interruption or
discontinuation of QALSODY. The most common adverse reactions that
occurred in ≥10% of QALSODY treated participants and more than the
placebo arm were pain, fatigue, arthralgia, CSF white blood cell
increased, and myalgia.
The efficacy of QALSODY was assessed in a 28-week randomized,
double-blind, placebo-controlled clinical study in patients 23 to
78 years of age with weakness attributable to ALS and a SOD1
mutation confirmed by a central laboratory. One hundred eight (108)
patients were randomized 2:1 to receive treatment with either
QALSODY 100 mg (n=72) or placebo (n=36) for 24 weeks (3 loading
doses followed by 5 maintenance doses). Concomitant riluzole and/or
edaravone use was permitted for patients and at baseline 62% of
patients were taking riluzone, and 8% of patients were taking
edaravone.
Over 28 weeks in VALOR, participants in the primary analysis
population (n=60) treated with QALSODY experienced less decline
from baseline as measured by the Revised Amyotrophic Lateral
Sclerosis Functional Rating Scale (ALSFRS-R) compared to placebo,
though the results were not statistically significant
(QALSODY-placebo adjusted mean difference [95% CI]: 1.2 [-3.2,
5.5]). In the overall intent-to-treat population (n=108),
QALSODY-treated participants experienced a 55% reduction in plasma
NfL compared to a 12% increase in placebo-treated participants
(difference in geometric mean ratios for QALSODY to placebo: 60%;
nominal p<0.0001). Additionally, levels of CSF SOD1
protein, an indirect measure of target engagement, were reduced by
35% in the QALSODY-treated group compared to 2% in the
corresponding placebo group (difference in geometric mean ratios
for QALSODY to placebo: 34%; nominal p<0.0001).
At an interim analysis at 52 weeks of participants who had
completed VALOR and enrolled in an open-label extension (OLE)
study, reductions in NfL were seen in participants previously
receiving placebo and who initiated QALSODY in the OLE, similar to
the reductions seen in participants treated with QALSODY in VALOR.
Earlier initiation of QALSODY compared to placebo/delayed-start of
QALSODY was associated with trends for reduction in decline on
measures of clinical function (ALSFRS-R), respiratory strength
(slow vital capacity percent-predicted), and muscle strength
(hand-held dynamometry megascore), though they were not
statistically significant. QALSODY was also associated with a
non-statistically significant trend towards reduction of the risk
of death or permanent ventilation. These exploratory analyses
should be interpreted with caution given the limitations of data
collected outside of controlled study, which may be subject to
confounding.
The approval of QALSODY was supported by 12-month integrated
results from VALOR and its OLE comparing earlier initiation of
tofersen (at the start of VALOR) to delayed initiation of tofersen
(six months later, in the OLE), that were published in The New
England Journal of Medicine.
What is QALSODY?
QALSODY™ (tofersen) is a prescription medicine used to
treat adults with amyotrophic lateral sclerosis (ALS) associated
with a mutation in the superoxide dismutase 1 (SOD1) gene.
This indication is approved under accelerated approval based on
reduction in plasma neurofilament light chain (NfL) observed in
patients treated with QALSODY. Continued approval for this
indication may be contingent upon verification of clinical benefit
in confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
What is the most important information that I should know
about QALSODY?
QALSODY can cause serious side effects, including:
Inflammation of the spinal cord (myelitis) and/ or irritation
of the nerve roots (radiculitis), including serious cases, have
been reported in patients treated with QALSODY. Contact your
healthcare provider to learn more about symptoms associated with
myelitis or radiculitis, and/ or if you believe you are
experiencing either of these conditions. QALSODY may need to
be interrupted or discontinued.
Swelling of the optic nerve (papilledema) and increased
pressure inside the skull (elevated intracranial pressure),
including serious cases, have been reported in patients treated
with QALSODY. Contact your healthcare provider to learn more about
symptoms associated with papilledema or elevated intracranial
pressure, and/ or if you believe you are experiencing either of
these conditions.
Inflammation of the brain linings (aseptic meningitis),
including serious cases, have been reported in patients treated
with QALSODY. Contact your healthcare provider to learn more about
symptoms associated with aseptic meningitis, and/ or if you believe
you are experiencing this condition.
What should I tell my HCP before I start using
QALSODY?
Before taking QALSODY, tell your healthcare provider if
you are pregnant, plan to become pregnant, or are breastfeeding or
plan to breastfeed.
What are the possible side effects of QALSODY?
The most common adverse reactions reported in patients
treated with QALSODY were pain (back pain, pain in arms or legs),
feeling tired, muscle and joint pain and increased white blood cell
count in the cerebrospinal fluid (CSF).
This information is not intended to replace discussions with
your healthcare provider.
These are not all the possible side effects of QALSODY.
Please talk to your healthcare provider if you experience any of
these symptoms, or other new symptoms that concern you.
Call your doctor for medical advice about side effects. You
may report side effects to FDA at 1-800-FDA-1088.
Please see full Prescribing Information.
For more details on QALSODY, visit www.QALSODY.com.
About QALSODY™ (tofersen)
QALSODY is an antisense oligonucleotide (ASO) designed to bind
to SOD1 mRNA to reduce SOD1 protein production. QALSODY is
indicated for the treatment of ALS in adults who have a mutation in
the SOD1 gene in the U.S. This indication is approved under
accelerated approval based on reduction in plasma NfL observed in
patients treated with QALSODY. Continued approval for this
indication may be contingent upon verification of clinical benefit
in confirmatory trial(s). QALSODY is administered intrathecally as
three loading doses administered at 14-day intervals followed by
maintenance doses administered once every 28 days thereafter. In
people with SOD1-ALS, mutations in their SOD1 gene
cause their bodies to create a toxic misfolded form of SOD1
protein. This toxic protein causes motor neurons to degenerate,
resulting in progressive muscle weakness, loss of function, and
eventually, death.
Biogen licensed tofersen from Ionis under a collaborative
development and license agreement.
In addition to the ongoing OLE of VALOR, QALSODY is being
studied in the Phase 3, randomized, placebo-controlled ATLAS study
to evaluate whether QALSODY can delay clinical onset when initiated
in presymptomatic individuals with a SOD1 genetic mutation
and biomarker evidence of disease activity (elevated plasma NfL).
The primary efficacy endpoint is the proportion of participants
with emergence of clinically manifest ALS. ATLAS is currently more
than 50 percent enrolled with clinical trial sites in 14 countries
worldwide with an estimated primary completion date in 2026. More
details about ATLAS (NCT04856982) can be found at
clinicaltrials.gov.
About Amyotrophic Lateral Sclerosis and SOD1-ALS
Amyotrophic 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.
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 known family history of the
disease. Currently, there are no genetically targeted treatment
options for ALS. SOD1-ALS is diagnosed in approximately 2% of all
ALS cases, impacting about 330 people in the United States. While there are medications
approved for broad ALS, no available treatments target a genetic
mutation associated with ALS. Approximately 5-10% of people with
ALS are thought to have a genetic form of the disease; however,
they may not have a known family history of the disease.
About Ionis' Neurology Franchise
Ionis' neurology franchise addresses all major brain regions and
central nervous system cell types and currently has three Phase 3
studies ongoing with 12 therapies in clinical development, several
of which Ionis plans to commercialize directly. Ionis is
discovering and developing potential treatments for many
neurological diseases for which there are few or no disease
modifying treatments, including common diseases like Alzheimer's
and Parkinson's as well as rare diseases such as amyotrophic
lateral sclerosis (ALS) and Alexander disease. Ionis has discovered
and developed three commercially available neurological disease
medicines, including the first approved treatment for spinal
muscular atrophy, a medicine to treat hereditary
transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), and now
QALSOLDY for SOD1-ALS.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been a 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 promising late-stage pipeline highlighted by
cardiovascular and neurological franchises. Our scientific
innovation began and continues with the knowledge that sick people
depend on us, which fuels our vision to become the leader in
genetic medicine, utilizing a multi-platform approach to discover,
develop and deliver life-transforming therapies.
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
QALSODY (tofersen), Ionis' technologies and Ionis' 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 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 Dec. 31, 2022, which is on file
with the Securities and Exchange Commission. Copies of this and
other documents are available from the Company.
In this press release, unless the context requires otherwise,
"Ionis," "Company," "we," "our" and "us" all refer to Ionis
Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals® is a registered trademark of
Ionis Pharmaceuticals.
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SOURCE Ionis Pharmaceuticals, Inc.