- Improvement observed in pancreatic function,
as measured by C-peptide response, following 24 weeks of treatment
with AMX0035; worsening is typically expected with disease
progression based on natural history studies of Wolfram
syndrome
- Longer-term data for all participants who
have completed Week 36 and Week 48 assessments showed sustained
improvement over time
- Improvements or stabilization observed across
all secondary endpoints, including measures of glycemic control,
vision, and patient- and clinician-reported impressions of overall
disease burden
- AMX0035 was generally well-tolerated in all
participants
- Amylyx plans to meet with the FDA and other
stakeholders to inform a Phase 3 program and expects to provide an
update in 2025
- Topline data to be presented during a live
webcast today at 1:30 p.m. ET
Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the
“Company”) today announced positive topline data from the Phase 2
open-label HELIOS clinical trial of AMX0035 (sodium phenylbutyrate
[PB] and taurursodiol [TURSO, also known as ursodoxicoltaurine]) in
12 adults living with Wolfram syndrome. Wolfram syndrome is a rare,
progressive, monogenic disease impacting approximately 3,000 people
in the U.S. HELIOS showed improvement in pancreatic function, as
measured by C-peptide response after 24 weeks of treatment with
AMX0035, the study’s primary efficacy endpoint, in contrast to the
expected decrease in pancreatic function with disease progression.
Similar overall improvements or stabilization were observed across
all secondary endpoints, including hemoglobin A1c (HbA1c), time in
target glucose range assessed by continuous glucose monitoring, and
visual acuity. Patient- and physician-reported global impressions
of change showed disease stability or improvement in all
participants, meeting prespecified responder criteria.
In addition, longer-term data for all participants who completed
Week 36 (n=10) and Week 48 (n=6) assessments showed sustained
improvement over time. Data from HELIOS are being presented today
at the International Society for Pediatric and Adolescent Diabetes
(ISPAD) 50th Annual Congress and during a webcast held by the
Company.
“The topline results of HELIOS indicate that AMX0035 has the
potential to favorably change the trajectory of Wolfram syndrome, a
progressive disease with no approved treatment options. These
results build on the interim data presented in April of this year
and show an improvement on multiple measures of pancreatic beta
cell function, glycemic control, and vision,” said Fumihiko Urano,
MD, PhD, Principal Investigator of the Phase 2 HELIOS clinical
trial in Wolfram syndrome and the Samuel E. Schechter Professor of
Medicine in the Division of Endocrinology, Metabolism & Lipid
Research at Washington University School of Medicine in St. Louis.
“In addition, the participants who reached their Week 36 or Week 48
assessments demonstrated sustained improvement over baseline in
C-peptide and HbA1c, which are objective laboratory measures of
pancreatic function and glycemic control. These data are
encouraging since Wolfram syndrome is a progressive disease.”
The analysis performed includes Week 24 data for all 12
participants and data for all participants who completed their Week
36 (n=10) and Week 48 (n=6) assessments as of the data cutoff. The
primary efficacy endpoint of the trial measures change from
baseline in C-peptide, an established, objective laboratory measure
of pancreatic beta cell function and a surrogate marker of glycemic
control, assessed using a mixed meal tolerance test (MMTT) at Week
24. Secondary and exploratory outcomes include the assessment of
other diabetic measures and other domains affected by the
disease.
HELIOS showed improvements in its primary endpoint of C-peptide
response with a change from baseline to Week 24 at 120 minutes of
+3.8 minutes*ng/mL (min*ng/mL) [standard error (SE): 19.3] in the
Intent to Treat group (N=12) and +20.2 min*ng/mL [SE: 11.2] in the
Per Protocol group (N=11). In addition, as outlined in the table
below, participants receiving AMX0035 had improved glycemic
control, as measured by markers of glucose metabolism; improved
visual acuity in some participants, as measured by the Snellen
chart; and improvement or stabilization of the disease, as measured
by the Clinician Reported Global Impression of Change (CGIC) and
Patient Reported Global Impression of Change (PGIC).
Week 24 ITT
(N=12)
Week 24 Per Protocol†
(N=11)
Week 36 (n=10)
Week 48 (n=6)
C-Peptide Response
(min*ng/mL) mean change in AUC from baseline over 120
minutes††
+3.8 (SE: 19.3)
+20.2 (SE: 11.2)
+30.7 (SE: 9.7)
+36.7 (SE: 19.6)
Hemoglobin A1c (%) change
from baseline
-0.09 (SE: 0.14)
-0.16 (SE: 0.13)
-0.35 (SE: 0.18)
-0.30 (SE: 0.31)
Absolute Time in Target
Glucose Range (%) change from baseline
+5.2 (SE: 3.6)
+5.7 (SE: 3.9)
+12.3 (SE: 4.0)
+5.8 (SE: 8.9)
Mean Exogenous Insulin Dose
(units/kg/2 weeks)
change from baseline
-0.01
-0.01
0.01
0.02
Visual Acuity (LogMAR)
change from baseline
-0.04 (SE: 0.06)
-0.04 (SE: 0.06)
Not Collected at this Time
Point
-0.11 (SE: 0.12)
Clinician Report Global
Impression of Change (CGIC) % meeting responder
criteria†††
100%
100%
100%
100%
Patient Reported Global
Impression of Change (PGIC) % meeting responder
criteria†††
100%
100%
100%
100%
† Upon genetic review, one
participant did not meet the inclusion/exclusion criteria for
HELIOS. This participant was found to have an autosomal recessive
mutation confirmed to be pathogenic on just one of the two alleles
and variant of uncertain significance on the other allele. This
participant was within normal range for C-peptide, glycemic
measures, and vision suggesting lack of typical Wolfram syndrome
phenotype. Data presented with and without this participant who
reached Week 24 (Intent to Treat and Per Protocol,
respectively).
†† In non-diabetic individuals,
C-peptide peaks after a meal at approximately ~30 minutes; in
Wolfram syndrome, peak is slower but generally was at or before 120
minutes in HELIOS. Area under the curve (AUC) over 120 minutes
after meal challenge reflects beta cell response to a meal. Amylyx
is currently planning to focus on 120-minute AUC as the C-peptide
measure for future studies.
††† HELIOS defines a “responder” on
both the CGIC and PGIC as no change or improvement given the
progressive nature of Wolfram syndrome.
The safety profile of AMX0035 in HELIOS was consistent with
prior safety data. AMX0035 was generally well-tolerated. All
adverse events (AEs) were mild or moderate, and there were no
serious AEs related to AMX0035 treatment. The most common AE was
diarrhea.
“These outcomes indicate that treatment with AMX0035 may result
in meaningful improvements across multiple measures of disease
progression,” said Camille L. Bedrosian, MD, Chief Medical Officer
of Amylyx. “Wolfram syndrome is a progressive disease that is
expected to consistently worsen over time, despite best supportive
care, because of the underlying endoplasmic reticulum stress and
mitochondrial dysfunction that occurs due to mutations in the WSF1
gene. AMX0035 is believed to target both of these critical
pathways. In addition, we are encouraged by the sustained
improvement observed in all participants who completed Week 36 or
Week 48 assessments, and we thank the Wolfram syndrome community
for their continued collaboration and support in researching the
potential of AMX0035. We continue to engage with stakeholders and
plan to meet with the FDA to inform a Phase 3 program.”
The FDA and the European Commission granted Orphan Drug
Designation to AMX0035 for the treatment of Wolfram syndrome in
November 2020 and August 2024, respectively. HELIOS Interim Data
in Wolfram Syndrome Virtual Webcast Details Amylyx will host a
virtual webcast with management and Fumihiko Urano, MD, PhD,
Principal Investigator of the HELIOS clinical trial and the Samuel
E. Schechter Professor of Medicine in the Division of
Endocrinology, Metabolism & Lipid Research at Washington
University School of Medicine in St. Louis, to discuss topline
HELIOS data today, October 17, 2024, at 1:30 p.m. ET. A live
webcast of the presentation can be accessed under “Events and
Presentations” in the Investor section of the Company’s website,
https://investors.amylyx.com/news-events/events, and will be
available for replay for 90 days following the event.
About the HELIOS Trial HELIOS (NCT05676034) is a
12-participant, single-site, single-arm, 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. Participants in HELIOS receive
AMX0035 for up to 96 weeks followed by a four-week safety
follow-up. Primary and secondary outcomes are assessed at Week 24
and at longer-term time points.
In September 2022, researchers from Washington University School
of Medicine in St. Louis, including Dr. Urano, in collaboration
with Amylyx, published preclinical data on AMX0035 in beta cell,
neuronal cell, and mouse models of Wolfram syndrome in the
peer-reviewed Journal of Clinical Investigation Insight.
About Wolfram Syndrome Wolfram syndrome is a rare,
monogenic neurodegenerative disease characterized by
childhood-onset diabetes, optic nerve atrophy, and
neurodegeneration. Common manifestations of Wolfram syndrome
include diabetes mellitus, optic nerve atrophy, central diabetes
insipidus, sensorineural deafness, neurogenic bladder, and
progressive neurologic difficulties. Genetic and experimental
evidence suggests that endoplasmic reticulum (ER) dysfunction is a
critical pathogenic component of Wolfram syndrome. The prognosis of
Wolfram syndrome is poor, and many people with the disease die
prematurely with severe neurological disabilities.
About AMX0035 AMX0035 is an oral, fixed-dose combination
of sodium phenylbutyrate (PB) and taurursodiol (TURSO; also known
as ursodoxicoltaurine outside of the U.S.). AMX0035 was designed to
slow or mitigate neurodegeneration by targeting endoplasmic
reticulum (ER) stress and mitochondrial dysfunction, two connected
central pathways that lead to cell death and neurodegeneration. We
believe that our proprietary combination of PB and TURSO and their
complementary mechanisms of action will allow us to synergistically
target abnormal cell death to better prevent neurodegeneration than
treatment targeted at either mechanism of action alone. AMX0035 is
being studied as a potential treatment for Wolfram syndrome and
progressive supranuclear palsy, two neurodegenerative diseases.
About Amylyx Pharmaceuticals Amylyx is committed to the
discovery and development of new treatment options for communities
with high unmet needs, including people living with serious and
fatal neurodegenerative diseases and endocrine conditions. Since
its founding, Amylyx has been guided by science to address
unanswered questions, keeping communities at the heart and center
of all decisions. Amylyx is headquartered in Cambridge,
Massachusetts. For more information, visit amylyx.com and follow us
on LinkedIn and X. For investors, please visit
investors.amylyx.com.
Forward-Looking Statements Statements contained in this
press release 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: the potential clinical
benefit for AMX0035 to help people living with Wolfram syndrome;
and interactions with regulatory authorities. Any forward-looking
statements in this press release 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’ Quarterly
Report on Form 10-Q for the quarter ended June 30, 2024, and
subsequent filings with the SEC. All forward-looking statements
contained in this press release 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20241017181662/en/
Media Amylyx Media Team +1 (857) 799-7274
amylyxmediateam@amylyx.com
Investors Lindsey Allen Amylyx Pharmaceuticals, Inc. +1
(857) 320-6244 Investors@amylyx.com
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