Amylyx Pharmaceuticals Announces Pivotal Phase 3 LUCIDITY Trial Design for GLP-1 Receptor Antagonist (Avexitide) in Post-Bariatric Hypoglycemia
04 Décembre 2024 - 1:30PM
Business Wire
- Pivotal Phase 3 LUCIDITY trial will evaluate
FDA-agreed upon primary outcome of reduction in hypoglycemia events
and designed to align as closely as possible with previous Phase 2
trial designs
- Amylyx expects first study participant dosed
in LUCIDITY in Q1 2025 and topline results in 2026
- Avexitide has FDA Breakthrough Therapy
Designation for the treatment of post-bariatric hypoglycemia and
Orphan Drug Designation
- Amylyx to present the Phase 3 LUCIDITY trial
design at the World Congress on Insulin Resistance, Diabetes &
Cardiovascular Disease on December 12-14
Amylyx Pharmaceuticals, Inc. (Nasdaq: AMLX) (“Amylyx” or the
“Company”) today announced the design of its pivotal Phase 3
LUCIDITY clinical trial for avexitide, an investigational,
first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist,
for the treatment of post-bariatric hypoglycemia (PBH). LUCIDITY is
designed to evaluate the FDA-agreed upon primary outcome of
reduction in hypoglycemia events and to have similar inclusion and
exclusion criteria to the previous Phase 2 trials of avexitide in
PBH. Amylyx expects that the first study participant will be dosed
in the first quarter of 2025, followed by expected completion of
recruitment in 2025, and anticipates topline data in 2026.
“We are excited to advance avexitide into a Phase 3 clinical
trial, marking a pivotal step toward bringing this investigational
therapy to people living with PBH,” said Joshua Cohen and Justin
Klee, Co-CEOs of Amylyx. “The consistent data from five clinical
trials of avexitide in PBH underscore avexitide’s potential to be
the first therapy approved for people living with PBH.”
LUCIDITY will be a multicenter, randomized, double-blind,
placebo-controlled Phase 3 clinical trial evaluating the efficacy
and safety of avexitide in participants with PBH following
Roux-en-Y gastric bypass (RYGB) surgery. The Phase 3 trial will be
conducted at approximately 20 sites in the U.S. Approximately 75
participants will be randomized 3:2 to receive either 90 mg of
avexitide subcutaneously once daily or placebo. The trial will
include a three-week run-in period and a 16-week double-blind
treatment period. Participants who complete the double-blind period
of the planned study will be eligible to enter an open-label
extension (OLE) period with a duration of 32 weeks. The primary
efficacy objective of LUCIDITY will evaluate the reduction in the
composite of Level 2 and Level 3 hypoglycemia events through Week
16. Safety and tolerability will also be evaluated.
“PBH is believed to result from an excessive GLP-1 response
leading to persistent, recurrent, and debilitating hypoglycemia
events that take a profound toll on someone’s quality of life.
Avexitide is designed to bind to the GLP-1 receptor and inhibit the
effects of excessive GLP-1 in PBH, mitigating hypoglycemia by
decreasing insulin secretion and stabilizing blood glucose levels.
We are excited to evaluate avexitide, which has FDA Breakthrough
Therapy and Orphan Drug Designations, in the Phase 3 LUCIDITY
trial, following two Phase 2 clinical studies that demonstrated
compelling clinical data supporting avexitide’s ability to
significantly reduce the rates of hypoglycemia events,” said
Camille L. Bedrosian, MD, Chief Medical Officer of Amylyx. “Our
goal in Phase 3 is to align the trial design as closely as possible
with the prior studies. Importantly, we believe LUCIDITY is well
powered to detect a treatment effect. We look forward to continuing
to collaborate with study investigators and the PBH community as we
seek to initiate LUCIDITY and advance avexitide through the
clinical development process.”
LUCIDITY was informed by data from five clinical trials of
avexitide in people with PBH showing consistent, dose-dependent
effects across studies. The five clinical trials include a Phase 1
trial, a single ascending dose trial, a multiple ascending dose
trial, and two Phase 2 trials:
- In the Phase 2 (PREVENT), 28-day, randomized,
placebo-controlled crossover trial (N=18), results showed a
significant reduction in rates of Level 2 and 3 hypoglycemia events
in participants with PBH after RYGB surgery following treatment
with 30 mg twice daily and 60 mg once daily of avexitide compared
with placebo. PREVENT’s primary endpoint was met with statistical
significance, showing both avexitide dosing regimens improved the
lowest glucose level (nadir) after a meal as measured during formal
mixed meal tolerance testing (MMTT). Mean plasma glucose nadir was
increased by 21% (p=0.001) and 26% (p=0.0002) following avexitide
30 mg twice daily and 60 mg once daily dosing, respectively,
compared to placebo.
- In the Phase 2b, 28-day, open-label, investigator-initiated,
crossover trial (N=16), 90 mg once daily and 45 mg twice daily of
avexitide met its primary endpoint and significantly reduced rates
of hypoglycemia events in participants following RYGB surgery and
other upper-gastrointestinal surgeries. Participants in the Phase
2b trial receiving 90 mg once daily of avexitide, the dose Amylyx
plans to evaluate in LUCIDITY, saw a statistically significant 53%
reduction in Level 2 hypoglycemia events (p=0.004) and a
statistically significant 66% reduction in Level 3 hypoglycemia
events (p=0.0003).
Avexitide was generally well tolerated, with a favorable safety
profile replicated across the clinical trials.
Amylyx will present the trial design at the World Congress on
Insulin Resistance, Diabetes & Cardiovascular Disease (WCIRDC)
in Los Angeles on December 12-14, 2024. Following the conclusion of
the poster presentation on December 12, the poster will be made
available on the “Publications” page of the Amylyx website.
About Avexitide
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). 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 inhibit the effect of GLP-1 to
mitigate hypoglycemia by decreasing insulin secretion and
stabilizing blood glucose levels. In PBH, excessive GLP-1 can lead
to the hypersecretion of insulin and subsequent debilitating
hypoglycemia events. In two Phase 2 PBH trials, avexitide
demonstrated highly statistically significant reductions in
hypoglycemia 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, or approximately 160,000 people, in the U.S. PBH
is thought to be caused by an excessive glucagon-like peptide-1
(GLP-1) response leading to hypoglycemia and impaired quality of
life. PBH can cause debilitating hypoglycemia events associated
with inadequate supply of glucose to the brain, known as
neuroglycopenia. Clinical manifestations can include impaired
cognition, loss of consciousness, and seizures. PBH is also
associated with a high degree of disability that can result in
major disruptions to independent living. There are no approved
therapies for PBH.
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 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, the potential of
avexitide as a treatment for PBH; expectations regarding the timing
of initiation of a Phase 3 trial of avexitide in PBH and the timing
of results from the trial; and expectations regarding the potential
for the results of a Phase 3 trial to support approval of
avexitide; the Company’s expectations regarding its financial
performance; and expectations regarding the Company’s cash runway
and longer-term strategy. Any forward-looking statements in this
press release and related comments in the Company's earnings
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 success,
cost, and timing of Amylyx’ program development activities; Amylyx’
ability to execute on its regulatory development plans and
expectations regarding the timing of results from its planned data
announcements and initiation of clinical studies; the risk that
early-stage results may not reflect later-stage results; Amylyx’
ability to fund operations, and the impact that global
macroeconomic uncertainty, geopolitical instability, and public
health events will have on Amylyx’ operations, as well as 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 earnings 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20241203046765/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
Amylyx Pharmaceuticals (NASDAQ:AMLX)
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