- Avexitide is a novel, first-in-class GLP-1
receptor antagonist with the potential to treat hyperinsulinemic
hypoglycemia
- FDA Breakthrough Therapy Designation granted
for avexitide for post-bariatric hypoglycemia (PBH) and congenital
hyperinsulinism
- Acquisition builds on Amylyx’ endocrine and
neuroscience expertise and aligns with pipeline focus of delivering
important potential treatment options to communities with high
unmet needs
- Phase 3 program for avexitide in PBH expected
to begin in Q1 2025, with data readout anticipated in 2026; FDA has
agreed to the primary endpoint expected to be utilized in Phase
3
- Data from two Phase 2 studies of avexitide in
people with PBH demonstrated highly statistically significant
reductions in severe hypoglycemic events, an endpoint supported by
the FDA
- Avexitide was generally well tolerated, with
a favorable safety profile replicated across five clinical trials
in people with PBH
- Management to host conference call and
webcast today at 8:00 a.m. Eastern Time
Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the
“Company”) today announced the acquisition of avexitide from Eiger
BioPharmaceuticals, Inc. (“Eiger”). Avexitide has been studied for
the potential treatment of hyperinsulinemic hypoglycemia to
date.
“Since Amylyx was founded, we have been guided by a rigorous
approach to our science to bring potential treatments to
communities with high unmet needs. When we reviewed all the
compelling data supporting avexitide, it clearly aligned with our
strategic scientific criteria, expertise, and community values, and
we are excited to build upon the important work done to date to
study this asset,” said Joshua Cohen and Justin Klee, Co-CEOs of
Amylyx.
Avexitide is an investigational, first-in-class glucagon-like
peptide-1 (GLP-1) receptor antagonist that has been evaluated in
five clinical trials for post-bariatric hypoglycemia (PBH) and has
also been studied in congenital hyperinsulinism (HI), two
indications characterized by hyperinsulinemic hypoglycemia. The
U.S. Food and Drug Administration (FDA) has granted avexitide
Breakthrough Therapy Designation for both indications, Rare
Pediatric Disease Designation in congenital HI, and Orphan Drug
Designation for the treatment of hyperinsulinemic hypoglycemia
(which includes PBH and congenital HI).
Avexitide is designed to bind to the GLP-1 receptor on
pancreatic islet beta cells and block the effect of GLP-1 to
mitigate hypoglycemia by decreasing insulin secretion and
stabilizing glucose levels. In PBH, excessive GLP-1 can lead to the
hypersecretion of insulin and subsequent severe hypoglycemic
events, including autonomic and neuroglycopenic symptoms if left
unaddressed.
In previous Phase 2 and Phase 2b studies in PBH, avexitide
showed statistically significant reductions in hypoglycemic events
characterized by low blood glucose, including severe hypoglycemic
events with altered mental and/or physical function requiring
assistance. FDA guidance for industry combined with initial FDA
feedback specific to the pivotal Phase 3 program of avexitide for
PBH suggest that reduction in hypoglycemia events could be an
endpoint to support approval following positive results from a
pivotal Phase 3 clinical trial.
Amylyx expects to begin the Phase 3 program for avexitide in PBH
in Q1 2025. Furthermore, Amylyx is actively engaging in discussions
with the broader congenital HI community, including experts in the
field, to develop a path forward based on promising Phase 2 study
results conducted at Children's Hospital of Philadelphia. Avexitide
will be added to Amylyx’ current pipeline programs that have been
in research and development for several years: AMX0035 for the
treatment of Wolfram syndrome, AMX0035 for the treatment of
progressive supranuclear palsy, and AMX0114, the Company’s
antisense oligonucleotide targeting calpain-2 for the treatment of
amyotrophic lateral sclerosis, or ALS.
Avexitide in PBH: Key Clinical Trial Results to Date
The following table shows key results from the Phase 2,
randomized, placebo-controlled crossover study (PREVENT) that
evaluated efficacy and safety of avexitide for treatment of PBH
following Roux-en-Y gastric bypass surgery. The results showed
that, compared with placebo, avexitide 30 mg twice daily (BID) and
60 mg once daily (QD) significantly increased mean plasma glucose
nadir (prespecified primary endpoint) and lowered insulin peak,
corresponding to 50% and 75% fewer participants requiring rescue
during mixed meal tolerance testing, respectively. Significant
reductions in rates of Levels 1, 2, and 3 hypoglycemia were
observed. Continuous glucose monitoring (CGM) demonstrated
reductions in time in hypoglycemia without induction of clinically
relevant hyperglycemia.
Outcomea
N=17
Avexitide 30 mg BID
Avexitide 60 mg QD
Improvement
vs. Placebo
p-value
Improvement
vs. Placebo
p-value
Post Prandial Glucose Nadir (Primary
Endpoint)
21% higher
0.001
26% higher
0.0002
Peak Insulin Level (Secondary
Endpoint)
23% lower
0.029
21% lower
0.042
Rate of Level 1 Hypoglycemia
30% lower
0.072
61% lower
0.001
Rate of Level 2 Hypoglycemia
40% lower
0.040
60% lower
0.004
Rate of Level 3 (Severe) Hypoglycemia
23% lower
0.22
56% lower
0.014
aLevel 1 hypoglycemia:
self-monitoring of blood glucose (SMBG) <70 mg/dL; Level 2
hypoglycemia: SMBG <54 mg/dL; Level 3 hypoglycemia: a severe
event characterized by altered mental and/or physical functioning
that requires assistance from another person for recovery.
Avexitide was generally well tolerated. The most common adverse
events were injection site bruising, headache, and nausea; these
occurred more often with placebo than either avexitide dose. No
participants withdrew due to adverse events.
A Phase 2b open-label, investigator-initiated, cross-over study
of higher dose avexitide (45 mg BID and 90 mg QD) was completed in
a broader eligible population of 16 participants with PBH following
Roux-en-Y gastric bypass surgery, vertical sleeve gastrectomy,
esophagectomy, Nissen fundoplication, or gastrectomy. This trial
met both its primary endpoint of number of diurnal Level 2
hypoglycemia events (glucose <54mg/dL) as measured by CGM as
well as its secondary endpoints, which includes the rate of Level 2
hypoglycemia, rate of Level 3 hypoglycemia, percent diurnal time
<70 mg/dL as measured by CGM, and percent diurnal time <54
mg/dL as measured by CGM.
Avexitide was successful in reducing the frequency of
hypoglycemia up to 65% and the amount of time in hypoglycemia up to
64%. The below table shows results of avexitide at both doses of 45
mg BID and 90 mg QD compared to medical nutrition therapy
alone.
Outcome
N=16
Avexitide 45 mg BID
Avexitide 90 mg QD
Decrease from
Baseline
p-value
Decrease from
Baseline
p-value
Rate of Level 1 Hypoglycemia
54% lower
0.003
68% lower
0.0005
Rate of Level 2 Hypoglycemia (Secondary
Endpoint)a
57% lower
0.003
53% lower
0.004
Rate of Level 3 (Severe) Hypoglycemia
(Secondary Endpoint)b
68% lower
0.0003
66% lower
0.0003
aRate of Level 2 hypoglycemia:
self-monitoring of blood glucose (SMBG) <54 mg/dL.
bRate of Level 3 hypoglycemia:
severe event characterized by altered mental and/or physical
function requiring assistance.
There were no reported serious adverse events, and adverse
events were mostly mild to moderate and resolved without medical
treatment. The most common adverse events included diarrhea,
headache, bloating, and injection site reaction/bruising. No
participant withdrew due to adverse events.
“PBH is a debilitating condition with no approved treatment
options, and we look forward to advancing this critical work with
avexitide into Phase 3 for individuals with PBH based on the
totality of data from five clinical trials, and informed by our
ongoing work to address endocrine and metabolic aspects of Wolfram
syndrome. We also are continuing our conversations with the
congenital HI community regarding the clinical development of
avexitide in congenital HI to develop a path forward,” said Camille
L. Bedrosian, MD, Chief Medical Officer of Amylyx. “While we are
excited to study this new scientific pathway in hyperinsulinemic
hypoglycemia, our research in ALS and other neurodegenerative
diseases continues through our AMX0035 and AMX0114 programs, guided
by the understanding that people living with these devastating
diseases have no time to wait – we must continue to research and
collaborate with urgency.”
Transaction Details
On July 9, 2024, Amylyx completed the acquisition of
substantially all of the rights, title and interests in, to and
under those assets and interests used by the seller in the
development, manufacture and commercialization of avexitide from
Eiger for $35.1 million plus the aggregate amount of determined
cure costs and assumed liabilities. As part of the transaction,
Amylyx assumed certain contractual obligations from Eiger,
including a 3% royalty on future sales of avexitide in PBH, if
approved, to certain academic institutions.
Investor Conference Call Information
Amylyx’ management team will host a conference call and webcast
today, July 10, 2024, at 8:00 a.m. ET to discuss the asset
acquisition. To access the conference call, please dial +1 (800)
836-8184 (U.S. and Canada) or +1 (646) 357-8785 (international) at
least 10 minutes prior to the start time and ask to be joined into
the Amylyx Pharmaceuticals call. A live audio webcast of the call
will be available 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 Avexitide
Avexitide is an investigational, first-in-class glucagon-like
peptide-1 (GLP-1) receptor antagonist that has been evaluated in
five Phase 2 clinical studies for post-bariatric hypoglycemia (PBH)
and has also been studied in congenital hyperinsulinism (HI), with
U.S. Food and Drug Administration (FDA) Breakthrough Therapy
Designation for both indications and FDA Rare Pediatric Disease
Designation in congenital HI. Avexitide is designed to bind to the
GLP-1 receptor on pancreatic islet beta cells and block the effect
of excessive GLP-1 to mitigate hypoglycemia by decreasing insulin
secretion and stabilizing glucose levels. In PBH, excessive GLP-1
can lead to the hypersecretion of insulin and subsequent severe
hypoglycemic events. In two Phase 2 PBH trials, avexitide
demonstrated highly statistically significant reductions in
hypoglycemic events. These events can lead to autonomic and
neuroglycopenic symptoms that can have a devastating impact on
daily living.
About Post-Bariatric Hypoglycemia (PBH)
Symptomatic post-bariatric hypoglycemia (PBH) is a condition
that affects approximately 8% of people who have undergone
bariatric surgery. It is characterized by exaggerated secretion of
glucagon-like peptide-1 (GLP-1), dysregulated secretion of insulin,
and a rapid drop in blood sugar. PBH can cause severe hypoglycemic
events associated with brain glucose starvation, known as
neuroglycopenia, including impaired cognition, cardiac arrythmias,
loss of consciousness, and seizures. PBH is associated with a high
degree of disability and can result in major disruptions to life,
including falls, motor vehicle accidents, and job and income loss.
It is estimated that ~160,000 people are currently living with
symptomatic PBH in the U.S., classifying it as an orphan
condition.
About Congenital Hyperinsulinism (HI)
Congenital hyperinsulinism (HI) is a rare disease characterized
by hypersecretion of insulin leading to severe, persistent
hypoglycemia in infants and young children with limited therapeutic
options. Common symptoms of congenital HI include lack of energy,
irritability, lethargy, and excessive hunger. Repeated episodes of
low blood glucose increase the risk for serious complications such
as breathing difficulties, seizures, intellectual disability,
vision loss, brain damage, and coma.
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.
Preclinical studies have provided evidence that the proprietary
combination of PB and TURSO and their complementary mechanisms of
action targets cell death and better prevents neurodegeneration
than targeting either mechanism of action alone. AMX0035 is being
studied as a potential treatment in neurodegenerative diseases,
including Wolfram syndrome and progressive supranuclear palsy
(PSP).
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 induced pluripotent stem cell
(iPSC)-derived human motor neurons, and improved survival of
iPSC-derived human motor neurons harboring ALS-linked, pathogenic
TDP-43 mutations.
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 diseases. 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
(formerly Twitter). 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: plans for initiating a Phase 3 clinical program of
avexitide, including interactions with regulatory authorities; the
possibility that results from a Phase 3 program could support FDA
approval of avexitide in PBH; and expectations regarding the
benefits of the acquisition of avexitide. 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’ 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 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/20240710172870/en/
Media Amylyx Media Team +1 (857) 799-7274
amylyxmediateam@amylyx.com
Investors Lindsey Allen +1 (857) 320-6244
Investors@amylyx.com
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