- PHOENIX Study Did Not Meet Prespecified
Primary or Secondary Endpoints
- Data From 664-Participant Study Reinforce
That AMX0035 is Generally Safe and Well-Tolerated
- Within the Next Eight Weeks, Amylyx Will
Continue to Engage With Regulatory Authorities and the ALS
Community to Share Topline Data; Amylyx Will Share Plans for
RELYVRIO/ALBRIOZA in ALS Which May Include Voluntarily Withdrawing
RELYVRIO/ALBRIOZA From the Market
- At This Time, RELYVRIO/ALBRIOZA Will Continue
to be Available for People Living With ALS; Amylyx Has Voluntarily
Decided to Pause Promotion; Related Patient Support Services Will
Remain in Place
- Studies With AMX0035 in Wolfram Syndrome (WS)
and Progressive Supranuclear Palsy (PSP) to Continue Based on Data
Supporting its Potential in These Diseases
- Amylyx to Host Investor Conference Call
Today, March 8, at 8:00 a.m. ET
Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the
“Company”) today announced topline results from PHOENIX, a global,
48-week, randomized, placebo-controlled Phase 3 clinical trial of
AMX0035 (sodium phenylbutyrate and taurursodiol [also known as
ursodoxicoltaurine]; RELYVRIO® in the U.S., ALBRIOZA™ in Canada) in
people living with amyotrophic lateral sclerosis (ALS). PHOENIX did
not meet its primary endpoint of reaching statistical significance
(p=0.667) as measured by change from baseline in the Revised
Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R)
total score at Week 48, nor was there statistical significance seen
in secondary endpoints. Amylyx plans to present the data from
PHOENIX at an upcoming medical meeting and will publish the results
in a medical journal later this year.
Amylyx will continue to engage with regulatory authorities and
the broader ALS community, including ALS specialists and other
multidisciplinary experts, people living with ALS, and advocates,
to discuss the results from PHOENIX within the next eight weeks and
make informed decisions. Amylyx intends to share plans for
RELYVRIO/ALBRIOZA in ALS, which may include voluntarily withdrawing
RELYVRIO/ALBRIOZA from the market. At this time, RELYVRIO/ALBRIOZA
and its related patient support program will continue to be
available for people living with ALS. Amylyx has voluntarily
decided to pause promotion of the medication during this time.
“We are surprised and deeply disappointed by the PHOENIX results
following the positive data from the CENTAUR trial. Our main
priority at the moment is sharing the information with people
living with ALS and their treating physicians; this is part of our
continued commitment to them and our mission. Over the next eight
weeks, our team will continue to engage with regulatory authorities
and the ALS community to discuss the results from PHOENIX. We will
be led in our decisions by two key principles: doing what is right
for people living with ALS, informed by regulatory authorities and
the ALS community, and by what the science tells us. On behalf of
the entire Amylyx team, we are grateful to the ALS community and
for the dedication of trial participants, investigators, and study
site teams. With data collected from 664 participants in PHOENIX,
we are certain there will be important learnings that will help
inform future ALS research. We are steadfast in our commitment to
the ALS community and our mission, including with AMX0035 where it
has shown potential in neurodegenerative diseases such as Wolfram
syndrome and progressive supranuclear palsy, and with AMX0114, our
investigational antisense oligonucleotide targeting calpain-2, in
ALS,” said Justin Klee and Joshua Cohen, Co-CEOs of Amylyx.
PHOENIX Study Results:
The Phase 3 PHOENIX study enrolled 664 adults living with ALS.
Participants were randomized three-to-two to receive either AMX0035
or placebo, with both treatment groups receiving standard-of-care.
Continuation of a stable dosing regimen of riluzole and/or
edaravone was permitted.
- PHOENIX did not meet the primary endpoint: There was no
significant difference observed between participants treated with
AMX0035 and placebo in ALSFRS-R total score change from baseline at
Week 48 (p=0.667). No significant difference was observed in the
subset of participants who met the CENTAUR trial criteria. There
were also no significant differences observed across secondary
endpoints.
- Consistent safety and tolerability profile: AMX0035 was
well-tolerated in PHOENIX. There were no new safety signals,
reinforcing the favorable and manageable safety profile observed
with AMX0035 to date.
- European participants who completed the 48-week randomized
phase had the option to enroll in an open label extension of the
trial of up to two years in duration, which remains ongoing.
Science of AMX0035:
AMX0035, a specially formulated oral fixed-dose combination of
PB and TURSO, has been shown in numerous preclinical studies to
have a robust, synergistic effect in targeting two different
destructive neurodegenerative disease pathways by mitigating
endoplasmic reticulum stress and the associated unfolded protein
response and mitochondrial dysfunction thereby reducing neuronal
cell death. Additionally, AMX0035 has been shown to also reduce
markers associated with neurodegenerative diseases in clinical
trials, including a reduction of tau, a key protein aggregate
shared across several neurodegenerative diseases, and YKL-40, a
marker of neuroinflammation.
Update on Ongoing AMX0035 Studies:
The global, randomized, double-blind, placebo-controlled Phase 3
ORION clinical study of AMX0035 in PSP remains ongoing. The first
participant was dosed in December 2023, and the Company is planning
for an interim analysis. Topline results continue to be anticipated
in 2025 or 2026.
Data from the ongoing 12-participant, single site, open-label
Phase 2 HELIOS clinical study are demonstrating evidence of
clinical activity of AMX0035 in Wolfram syndrome. This study is
fully recruited, and the Company plans to present preliminary data
in the second quarter of 2024.
Investor Conference Call Information
Amylyx’ management team will host a live conference call and
webcast today, March 8, 2024, at 8:00 a.m. ET to discuss the
results of the PHOENIX trial. To participate in the conference
call, please dial +1 (877) 870-4263 (U.S.), +1 (855) 669-9657
(Canada), or +1 (412) 317-0790 (International) at least 10 minutes
prior to the start time and ask to be joined into the Amylyx
Pharmaceuticals call. All interested parties are invited to access
a live broadcast of the call via a webcast, which will be available
on the “Events and Presentations” page in the “Investors” section
of the Company’s website at
investors.amylyx.com/news-events/events. An archived webcast will
be available on the Company's website approximately two hours after
the conference call and will be available for replay for 90 days
following the call.
About the PHOENIX Trial
PHOENIX was a 48-week, randomized, placebo-controlled, global
Phase 3 clinical trial further evaluating the safety and efficacy
of AMX0035 (sodium phenylbutyrate and taurursodiol) for the
treatment of ALS. The primary efficacy outcome of the trial was
change from baseline in ALS Functional Rating Scale-Revised
(ALSFRS-R) total score at 48 weeks. Secondary endpoints include
quality of life patient-reported outcome assessments, overall
survival, and respiratory function as measured by slow vital
capacity (SVC). Safety and tolerability were also assessed.
European participants who completed the 48-week trial had the
option to enroll in an open-label extension (OLE) phase. During
this phase, all participants receive AMX0035, and continued safety
and efficacy measures will be assessed.
About the CENTAUR Trial
CENTAUR was a multicenter Phase 2 clinical trial in 137
participants with ALS encompassing a 6-month randomized,
placebo-controlled phase and an open-label long-term follow-up
phase. The trial met its primary efficacy endpoint of reducing
functional decline as measured by the ALS Functional Rating
Scale-Revised (ALSFRS-R).
Overall, reported rates of adverse events and discontinuations
were similar between AMX0035 and placebo groups during the 24-week
randomized phase; however, gastrointestinal events occurred with
greater frequency (≥2%) in the AMX0035 group. Detailed data from
CENTAUR is published in the New England Journal of Medicine (NEJM)
and Muscle & Nerve.
The CENTAUR trial was funded, in part, by the ALS ACT grant and
the ALS Ice Bucket Challenge, and was supported by The ALS
Association, ALS Finding a Cure (a program of The Leandro P.
Rizzuto Foundation), the Northeast ALS Consortium, and the Sean M.
Healey & AMG Center for ALS at Mass General.
About AMX0114
AMX0114 is an antisense oligonucleotide designed to target the
gene encoding calpain-2, a key contributor to the axonal
(Wallerian) degeneration pathway. Axonal degeneration has been
recognized as an important early contributor to the clinical
presentation and pathogenesis of ALS and other neurodegenerative
diseases. Calpain-2 has been implicated in the pathogenesis of ALS
based on findings of elevated levels of calpain-2 and its cleavage
products in postmortem ALS tissue, therapeutic benefit of calpain-2
modulation in animal models of ALS, and the role of calpain-2 in
cleaving neurofilament, a broadly researched biomarker in ALS.
Preclinical studies completed to date have shown that AMX0114
achieves potent, dose-dependent, and durable knockdown of CAPN2
mRNA expression and calpain-2 protein levels in human motor
neurons. Moreover, in preclinical efficacy studies, treatment with
AMX0114 reduced extracellular neurofilament light chain levels
following neurotoxic insult in iPSC-derived human motor neurons,
and improved survival of iPSC-derived human motor neurons harboring
ALS-linked, pathogenic TDP-43 mutations.
About ALS
Amyotrophic lateral sclerosis (ALS, also known as motor neuron
disease) is a relentlessly progressive and fatal neurodegenerative
disorder caused by motor neuron death in the brain and spinal cord.
Motor neuron loss in ALS leads to deteriorating muscle function,
the inability to move and speak, respiratory paralysis, and
eventually, death. More than 90% of people with ALS have sporadic
disease, showing no clear family history. ALS affects around 30,000
people in the U.S., and more than 30,000 people are estimated to be
living with ALS in Europe (European Union and United Kingdom).
People living with ALS have a median survival of approximately two
years from diagnosis.
About HELIOS
The HELIOS trial (NCT05676034) is a 12-participant, open-label
proof of biology, Phase 2 trial designed to study the effect of
AMX0035 on safety and tolerability, and various measures of
endocrinological, neurological, and ophthalmologic function in
adult participants living with Wolfram syndrome (WS).
About Wolfram Syndrome
Wolfram syndrome (WS) is an autosomal recessive
neurodegenerative disease characterized by childhood-onset
diabetes, optic nerve atrophy, and neurodegeneration. Common
manifestations of WS include diabetes mellitus, optic nerve
atrophy, central diabetes insipidus, sensorineural deafness,
neurogenic bladder, and progressive neurologic difficulties.
Genetic and experimental evidence suggest that endoplasmic
reticulum (ER) dysfunction is a critical pathogenic component of
WS. The prognosis of WS is poor, and many people with the disease
die prematurely with severe neurological disabilities.
About the ORION Trial
The Phase 3 ORION trial (NCT06122662) is a global, randomized,
double-blind, placebo-controlled Phase 3 clinical trial designed to
assess the efficacy, safety, and tolerability of AMX0035 compared
to placebo in people living with progressive supranuclear palsy
(PSP). The ORION Phase 3 trial was designed and planned in
collaboration with key global academic leaders, people living with
PSP and their caregivers, and industry advocacy organizations.
About PSP
Progressive supranuclear palsy (PSP) is a sporadic, rare and
adult-onset neurodegenerative disorder that affects walking and
balance, eye movement, swallowing, and speech. People living with
PSP have a life expectancy of six to eight years after initial
diagnosis, and its epidemiology is similar to that of amyotrophic
lateral sclerosis (ALS). PSP typically begins in late-middle age
and rapidly progresses over time. The disease affects approximately
seven in 100,000 people worldwide, and there are currently no
disease-modifying therapies approved for the treatment of PSP.
PSP is characterized by abnormal tau inclusions and is
consequently also known as a tauopathy. Similar to other
neurodegenerative diseases, pathophysiologic changes underlying PSP
are multifactorial with several genetic and environmental factors
likely contributing to tau dysfunction and aggregation.
Multiple pathways, including genetic mutations, endoplasmic
reticulum (ER) stress and the activation of unfolded protein
response, mitochondrial dysfunction, and neuroinflammation have
been implicated as contributors to tau dysfunction and
aggregation.
About AMX0035 / RELYVRIO® / ALBRIOZA™
AMX0035 is an oral, fixed-dose combination of sodium
phenylbutyrate and taurursodiol (known as ursodoxicoltaurine
outside of the U.S.). It is approved as RELYVRIO® to treat
amyotrophic lateral sclerosis (ALS) in adults in the U.S. and
approved with conditions as ALBRIOZA™ for the treatment of ALS in
Canada. AMX0035 is being studied for the potential treatment of
other neurodegenerative diseases, and Amylyx is exploring its
treatment in other populations and regions. The formulation of
RELYVRIO, ALBRIOZA, and AMX0035 is identical.
RELYVRIO® (sodium phenylbutyrate and taurursodiol) Safety
Information for United States
WARNINGS AND PRECAUTIONS
Risk in Patients with Enterohepatic Circulation Disorders,
Pancreatic Disorders, or Intestinal Disorders
RELYVRIO contains taurursodiol, which is a bile acid. In
patients with disorders that interfere with bile acid circulation,
there may be an increased risk for worsening diarrhea, and patients
should be monitored appropriately for this adverse reaction.
Pancreatic insufficiency, intestinal malabsorption, or intestinal
diseases that may alter the concentration of bile acids may also
lead to decreased absorption of either of the components of
RELYVRIO. Because different enterohepatic circulation, pancreatic,
and intestinal disorders have varying degrees of severity, consider
consulting with a specialist. Patients with disorders of
enterohepatic circulation (e.g., biliary infection, active
cholecystitis), severe pancreatic disorders (e.g., pancreatitis),
and intestinal disorders that may alter concentrations of bile
acids (e.g., ileal resection, regional ileitis) were excluded from
the study; therefore, there is no clinical experience in these
conditions.
Use in Patients Sensitive to High Sodium Intake
RELYVRIO has a high salt content. Each initial daily dosage of 1
packet contains 464 mg of sodium; each maintenance dosage of 2
packets daily contains 928 mg of sodium. In patients sensitive to
salt intake (e.g., those with heart failure, hypertension, or renal
impairment), consider the amount of daily sodium intake in each
dose of RELYVRIO and monitor appropriately.
ADVERSE REACTIONS
The most common adverse reactions (at least 15% and at least 5%
greater than placebo) with RELYVRIO were diarrhea, abdominal pain,
nausea, and upper respiratory tract infection.
Gastrointestinal-related adverse reactions occurred throughout the
study but were more frequent during the first 3 weeks of
treatment.
Please click here for RELYVRIO Full U.S.
Prescribing Information.
About Amylyx Pharmaceuticals
Amylyx Pharmaceuticals, Inc. is committed to supporting and
creating more moments for the neurodegenerative disease community
through the discovery and development of innovative new treatments.
Amylyx is headquartered in Cambridge, Massachusetts and has
operations in Canada, EMEA, and Japan. For more information, visit
amylyx.com and follow us on LinkedIn and X, (formerly Twitter). For
investors, please visit investors.amylyx.com.
Forward-Looking Statements
Statements contained in this press release and related comments
in our earnings conference call regarding matters that are not
historical facts are “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995, as
amended. Because such statements are subject to risks and
uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Such
statements include, but are not limited to, Amylyx’ expectations
regarding: interactions with regulatory authorities; the continued
availability of RELYVRIO/ALBRIOZA for people living with ALS while
such interactions are ongoing; the pausing of promotion of
RELYVRIO/ALBRIOZA; pathways for continued access for patients if
RELYVRIO/ALBRIOZA are withdrawn from the market; the possibility
for Amylyx to voluntarily withdraw RELYVRIO/ALBRIOZA from the
market; the continued evaluation of AMX0035 in other
neurodegenerative diseases, including the timing for expected data
readouts in the ORION and HELIOS studies; and the evidence of
biological activity of AMX0035 in Wolfram syndrome. Any
forward-looking statements in this press release and related
comments in the Company's conference call are based on management’s
current expectations of future events and are subject to a number
of risks and uncertainties that could cause actual results to
differ materially and adversely from those set forth in or implied
by such forward-looking statements. Risks that contribute to the
uncertain nature of the forward-looking statements include the
risks and uncertainties set forth in Amylyx’ United States
Securities and Exchange Commission (SEC) filings, including Amylyx’
Annual Report on Form 10-K for the year ended December 31, 2023,
and subsequent filings with the SEC. All forward-looking statements
contained in this press release and related comments in our
conference call speak only as of the date on which they were made.
Amylyx undertakes no obligation to update such statements to
reflect events that occur or circumstances that exist after the
date on which they were made.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240308462671/en/
Media Amylyx Media Team (857) 799-7274
amylyxmediateam@amylyx.com Investors Lindsey Allen (857)
320-6244 Investors@amylyx.com
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