FDA Grants Accelerated Approval for QALSODY™ (tofersen) for
SOD1-ALS, a Major Scientific Advancement as the First Treatment to
Target a Genetic Cause of ALS
Biogen Inc. (Nasdaq: BIIB) announced today that the U.S. Food and
Drug Administration (FDA) has approved 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 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).1 The
ongoing Phase 3 ATLAS study of tofersen in people with
presymptomatic SOD1-ALS will serve as the confirmatory trial.1
Neurofilaments are proteins that are released from neurons when
they are damaged, making them a marker of neurodegeneration.6
“For more than a decade, Biogen has been steadfast in our
commitment to pursuing treatments for ALS, and I want to thank the
scientists as well as the entire ALS community who have all worked
tirelessly to bring this first-of-its-kind treatment to people with
SOD1-ALS,” said Christopher A. Viehbacher, President and Chief
Executive Officer of Biogen. “Today also marks a pivotal moment in
ALS research as we gained, for the first time, consensus that
neurofilament can be used as a surrogate marker reasonably likely
to predict clinical benefit in SOD1-ALS. We believe this important
scientific advancement will further accelerate innovative drug
development for ALS.”
QALSODY is the first approved treatment to target a genetic
cause of ALS.1 Biogen collaborated with Ionis Pharmaceuticals on
the early development of tofersen.
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, cerebrospinal (CSF)
white blood cell increased, and myalgia.1
“Since SOD1 mutations were first identified as a cause of ALS 30
years ago, the familial ALS community has been searching for
genetically targeted treatments. QALSODY offers families who have
lost generation after generation in the prime of their life to this
devastating disease a therapy targeting the underlying cause of
SOD1-ALS. Today marks an important moment in ALS research as
QALSODY is the first ALS treatment approved based on a biomarker,”
said Jean Swidler, chair of Genetic ALS & FTD: End the Legacy.
“We are excited to see what future therapies are developed now that
it is understood that lowering levels of neurofilament provides
important evidence that a treatment is affecting the
neurodegenerative process.”
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.1
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).1
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.1
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.7
“I have observed the positive impact QALSODY has on slowing the
progression of ALS in people with SOD1 mutations,” said Timothy M.
Miller, MD, PhD, principal investigator of the QALSODY clinical
trials and co-director of the ALS Center at Washington University
School of Medicine in St. Louis. “The FDA’s approval of QALSODY
gives me hope that people living with this rare form of ALS could
experience a reduction in decline in strength, clinical function,
and respiratory function.”
QALSODY will be made available for shipment in the U.S. to
healthcare providers in approximately one week. Biogen anticipates
there may be variation in time to treatment as institutions and
treatment centers learn about QALSODY.
What is QALSODY?QALSODYTM (tofersen) is a
prescription medicine used to treat 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 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.1 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.8
Biogen licensed tofersen from Ionis Pharmaceuticals, Inc. under
a collaborative development and license agreement. Tofersen was
discovered by Ionis.
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.
Financial Assistance Programs and Access to
QALSODY Biogen provides comprehensive support
services which includes insurance couseling and financial
assistance for eligible individuals. Support Coordinators are
available to help with understanding insurance coverage, navigating
the access landscape, and exploring financial assistance options
including the QALSODY (tofersen) Copay Program, which may lower the
out-of-pocket costs for eligible commercially insured patients to
as low as $0. They can be reached at 1-877-725-7639 between the
hours of 8:30 AM – 8:00 PM ET, Monday to Friday.
ALS Identified™ ProgramUp to 15 percent of
people living with ALS are thought to have a genetic form of the
disease, whether or not they have a known family history. As
genetic testing is not broadly available, Biogen sponsors a genetic
testing program, ALS Identified™, for people living with ALS and
their families in the U.S.
Sponsored by Biogen and offered through Invitae, the ALS
Identified™ program facilitates access to genetic counseling and
testing for all individuals 18 years or older within the U.S. and
Puerto Rico with a clinical diagnosis of ALS, or a family history
of ALS at no charge. More information about ALS Identified is
available at insideALS.com, a website designed in collaboration
with outside medical experts and the ALS community that offers
continuous updates on the emerging science that provides insights
and information to the ALS community. Interested people with ALS
should talk to their doctor about genetic testing options and can
learn more at insideALS.com.
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.2
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. SOD1-ALS is diagnosed in approximately 2 percent of all
ALS cases, with about 330 people in the United States living with
the disease.5 More than 15 percent of people with ALS are thought
to have a genetic form of the disease;8 however, they may not have
a known family history of the disease.5
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. In addition to QALSODY, the
company has a pipeline of investigational drugs being evaluated in
ALS, including BIIB105.
About BiogenFounded in 1978, Biogen is a
leading global biotechnology company that has pioneered multiple
breakthrough innovations including a broad portfolio of medicines
to treat multiple sclerosis, the first approved treatment for
spinal muscular atrophy, and two co-developed treatments to address
a defining pathology of Alzheimer’s disease. Biogen is advancing a
pipeline of potential novel therapies across neurology,
neuropsychiatry, specialized immunology and rare diseases and
remains acutely focused on its purpose of serving humanity through
science while advancing a healthier, more sustainable and equitable
world. We routinely post information that may be important to
investors on our website at www.biogen.com. Follow us on
social
media - Twitter, LinkedIn, Facebook, YouTube.
Biogen Safe Harbor This news release
contains forward-looking statements, the potential clinical effects
of QALSODY; the potential benefits, safety and efficacy of QALSODY;
the clinical development program for QALSODY; 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 QALSODY; 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 our
forward-looking statements.
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 speak only as of the date
of this news release.
We do not undertake any obligation to publicly update any
forward-looking statements.
References:
- QALSODY Prescribing Information, Cambridge, MA: Biogen.
- National Institute of Neurological Disorders and Stroke.
Amyotrophic Lateral Sclerosis (ALS). Available at:
https://www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als.
Accessed: April 2023.
- Frederiksen SD, Avramović V, Maroilley T, et al. Rare disorders
have many faces: in silico characterization of rare disorder
spectrum. Orphanet J Rare Dis. 2022 Feb 22;17(1):76. doi:
10.1186/s13023-022-02217-9.
- Hee SW, Willis A, Tudur Smith C, et al. Does the low prevalence
affect the sample size of interventional clinical trials of rare
diseases? An analysis of data from the aggregate analysis of
clinicaltrials.gov. Orphanet J Rare Dis. 2017 Mar 2;12(1):44. doi:
10.1186/s13023-017-0597-1.
- Brown CA, Lally C, Kupelian V, Flanders WD. Estimated
Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1
and C9orf72 Genetic Variants. Neuroepidemiology.
2021;55(5):342-353. doi: 10.1159/000516752. Epub 2021 Jul 9.
- Yuan A, Rao MV, Veeranna, Nixon RA. Neurofilaments and
Neurofilament Proteins in Health and Disease. Cold Spring Harb
Perspect Biol. 2017;9(4):a018309.
- Miller TM, Cudkowicz ME, Genge A, et al. Trial of Antisense
Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med.
2022;387:1099-110. doi: 10.1056/NEJMoa2204705.
- Akcimen F, Lopez ER, Landers JE, et al. Amyotrophic lateral
sclerosis: translating genetic discoveries into therapies. Nat Rev
Genet. 2023. https://doi.org/10.1038/s41576-023-00592-y
MEDIA
CONTACT:BiogenJack Cox+ 1 210 544
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