-- Continued Improvements in RSBQ and CGI-I
scores seen with long-term DAYBUE treatment in Phase 3 LAVENDER™
and LILAC studies
-- DAYBUE safety profile was consistent with
findings from the LAVENDER trial
Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that
the journal Med published results from two open-label extension
studies, LILAC-1™ and LILAC-2™, which showed that patients treated
with DAYBUE™ who completed these studies experienced improvement in
Rett symptoms as measured by the Rett Syndrome Behaviour
Questionnaire (RSBQ). LILAC-1 was a 40-week, open-label extension
study of the 12-week Phase 3 LAVENDER™ trial, evaluating the
long-term safety and efficacy of DAYBUE in patients with Rett
syndrome five to 21 years of age. LILAC-2 was a 32-month open-label
extension study, evaluating the long-term safety and efficacy of
DAYBUE in females aged five to 22 years who completed LILAC-1. The
most common side effects reported in these studies were diarrhea
and vomiting. Results from both studies also showed DAYBUE’s safety
profile was consistent with results from the LAVENDER trial.
“These data from the open-label extension LILAC studies provide
deeper insight into the long-term safety and potential benefit of
DAYBUE for patients with Rett syndrome,” said Alan Percy, M.D.,
Professor of Pediatrics, Neurology, Neurobiology, Genetics, and
Psychology at University of Alabama, Birmingham and lead author for
the LILAC-1 and LILAC-2 studies. “These publications add to the
growing body of research on clinical experience with DAYBUE and its
potential ongoing impact for those living with this condition.”
“These findings from LILAC-1 and LILAC-2 add to the results from
the pivotal Phase 3 LAVENDER trial and the ongoing LOTUS real-world
evidence study and include patients who have been on treatment for
over two years, contributing to a robust and growing portfolio of
impactful data furthering our understanding of DAYBUE for the
treatment of Rett syndrome,” said Ponni Subbiah, M.D., M.P.H.,
Acadia’s Senior Vice President, Global Head of Medical Affairs and
Chief Medical Officer.
About the data:
- In LILAC-1, 154 females with Rett syndrome five to 21 years of
age received open-label treatment with DAYBUE for 40 weeks
following double-blind treatment with DAYBUE (n = 69) or placebo (n
= 85) in the 12-week LAVENDER study. The RSBQ mean (SE) change from
LAVENDER baseline to week 40 in LILAC-1 was −7.3 (1.62) for
participants who had been treated with DAYBUE in LAVENDER and
completed the LILAC-1 study (N=44) and −7.0 (1.61) for participants
who had been treated with placebo in LAVENDER and then were
switched to DAYBUE in LILAC-1 and completed LILAC-1 (N=44). Changes
from LAVENDER baseline to LILAC-1 week 40 for all RSBQ domain
subscores were directionally in favor of DAYBUE regardless of
treatment during LAVENDER, irrespective of age, baseline RSBQ
severity or underlying MECP2 mutation severity. Mean (SE) Clinical
Global Impression–Improvement (CGI-I) scores at week 40 compared to
LILAC-1 baseline were 3.1 (0.11) and 3.2 (0.14) for participants
who had been treated with DAYBUE or placebo in LAVENDER and
completed the LILAC-1 study, respectively.
- In the 32-month LILAC-2 study, 77 participants who completed
LILAC-1 continued to receive open-label treatment with DAYBUE for
up to an additional 104 weeks. Improvements in RSBQ scores were
reported for participants treated with DAYBUE with a score decrease
of ≥ 10% reported in 81.8% of participants at week 104. The mean
(SE) change in RSBQ score from LAVENDER baseline to week 104 of
LILAC-2 was −9.8 (3.38) for participants who had been treated with
DAYBUE in LAVENDER and completed the LILAC-2 study (N=11), and
−13.8 (3.61) for participants who received placebo in LAVENDER and
completed the LILAC-2 study (N=11). The mean CGI-I from LILAC-1
baseline to Week 12 of LILAC-2 was 3.1 (0.10) for the overall
population. 20.8% of patients had discontinued the study.
- 27 caregivers of 26 study participants took part in optional
exit interviews to explore the patients’ experiences with Rett
syndrome and DAYBUE during the trials. The most frequently reported
improvements observed by caregivers to participants treated with
DAYBUE in the studies were engagement with others (46.2%), hand use
(42.3%), and eye gaze (30.8%). Caregivers also reported that some
participants acquired new sounds (23.1%) or words (19.2%).
- The safety profile of DAYBUE in LILAC-1 and LILAC-2 was
consistent with the safety profile demonstrated in LAVENDER. The
most common adverse events in LILAC-1 were diarrhea (74.7%) and
vomiting (28.6%) with most reports of diarrhea as mild or moderate
in severity and all reports of vomiting as mild or moderate in
severity. In LILAC-2, the most common adverse events were diarrhea
(53.2%), COVID-19 (27.3%), and vomiting (19.5%). The studies were
conducted during the COVID pandemic. All reports of diarrhea were
of mild or moderate severity and most reports of vomiting (93.3%)
were mild or moderate in severity.
About Rett Syndrome
Rett syndrome is a rare, complex, neurodevelopmental disorder
that may occur over four stages and affects approximately 6,000 to
9,000 patients in the U.S., with approximately 5,000 patients
currently diagnosed according to an analysis of healthcare claims
data.1-4 A child with Rett syndrome exhibits an early period of
apparently normal development until six to 18 months, when their
skills seem to slow down or stagnate. This is typically followed by
a duration of regression when the child loses acquired
communication skills and purposeful hand use. The child may then
experience a plateau period in which they show mild recovery in
cognitive interests, but body movements remain severely diminished.
As they age, those living with Rett may continue to experience a
stage of motor deterioration which can last the rest of the
patient’s life.3 Rett syndrome is typically caused by a genetic
mutation on the MECP2 gene.5 In preclinical studies, deficiency in
MeCP2 function is thought to lead to impairment in synaptic
communication, and the deficits in synaptic function may be
associated with Rett manifestations.5-7
Symptoms of Rett syndrome may also include development of hand
stereotypies, such as hand wringing and clapping, and gait
abnormalities.8 Most Rett patients typically live into adulthood
and require round-the-clock care.2,9
About DAYBUE™ (trofinetide)
Trofinetide is a synthetic analog of the N-terminal tripeptide
of insulin-like growth factor 1. The mechanism by which trofinetide
exerts therapeutic effects in patients with Rett syndrome is
unknown. In animal studies, trofinetide has been shown to increase
branching of dendrites and synaptic plasticity signals.10
Important Safety Information for DAYBUE™
(trofinetide)
- Warnings and Precautions
- Diarrhea: In a 12-week study and in long-term studies,
an aggregate of 85% of patients treated with DAYBUE experienced
diarrhea. In those treated with DAYBUE, 49% either had persistent
diarrhea or recurrence after resolution despite dose interruptions,
reductions, or concomitant antidiarrheal therapy. Diarrhea severity
was of mild or moderate severity in 96% of cases. In the 12-week
study, antidiarrheal medication was used in 51% of patients treated
with DAYBUE. Patients should stop taking laxatives before starting
DAYBUE. If diarrhea occurs, patients should notify their healthcare
provider, consider starting antidiarrheal treatment, and monitor
hydration status and increase oral fluids, if needed. Interrupt,
reduce dose, or discontinue DAYBUE if severe diarrhea occurs or if
dehydration is suspected.
- Weight Loss: In the 12-week study, 12% of patients
treated with DAYBUE experienced weight loss of greater than 7% from
baseline, compared to 4% of patients who received placebo. In
long-term studies, 2.2% of patients discontinued treatment with
DAYBUE due to weight loss. Monitor weight and interrupt, reduce
dose, or discontinue DAYBUE if significant weight loss occurs.
- Adverse Reactions: The common adverse reactions (≥5% for
DAYBUE-treated patients and at least 2% greater than in placebo)
reported in the 12-week study were diarrhea (82% vs 20%), vomiting
(29% vs 12%), fever (9% vs 4%), seizure (9% vs 6%), anxiety (8% vs
1%), decreased appetite (8% vs 2%), fatigue (8% vs 2%), and
nasopharyngitis (5% vs 1%).
- Drug Interactions: Effect of DAYBUE on other Drugs
- DAYBUE is a weak CYP3A4 inhibitor; therefore, plasma
concentrations of CYP3A4 substrates may be increased if given
concomitantly with DAYBUE. Closely monitor when DAYBUE is used in
combination with orally administered CYP3A4 sensitive substrates
for which a small change in substrate plasma concentration may lead
to serious toxicities.
- Plasma concentrations of OATP1B1 and OATP1B3 substrates may be
increased if given concomitantly with DAYBUE. Avoid the concomitant
use of DAYBUE with OATP1B1 and OATP1B3 substrates for which a small
change in substrate plasma concentration may lead to serious
toxicities.
- Use in Specific Population: Renal Impairment
- DAYBUE is not recommended for patients with moderate or severe
renal impairment.
DAYBUE is available as an oral solution (200 mg/mL).
Please read the accompanying full Prescribing Information, also
available at DAYBUE.com
About Acadia Pharmaceuticals
Acadia is advancing breakthroughs in neuroscience to elevate
life. For 30 years we have been working at the forefront of
healthcare to bring vital solutions to people who need them most.
We developed and commercialized the first and only FDA-approved
drug to treat hallucinations and delusions associated with
Parkinson’s disease psychosis and the first and only FDA-approved
drug for the treatment of Rett syndrome. Our clinical-stage
development efforts are focused on Prader-Willi syndrome,
Alzheimer’s disease psychosis and multiple other programs targeting
neuropsychiatric symptoms in central nervous system disorders. For
more information, visit us at Acadia.com and follow us on LinkedIn
and Twitter.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements include all statements other than
statements of historical fact and can be identified by terms such
as “intends,” “may,” “will,” “should,” “could,” “would,” “expects,”
“plans,” “anticipates,” “believes,” “estimates,” “projects,”
“predicts,” “potential” and similar expressions (including the
negative thereof) intended to identify forward-looking statements.
Forward-looking statements contained in this press release,
include, but are not limited to, statements about: (i) the clinical
benefits of DAYBUE and continued statistically significant efficacy
observed in the DAYBUE Phase 3 clinical trial program and LILAC-1
and LILAC-2 open label extension studies, (ii) the safety and
tolerability profile of DAYBUE and anticipated Rett syndrome
symptom improvements, and (iii) the timing and outcome of future
results from, and continued enrollment and possible participation
extensions in, the real world, observational LOTUS study.
Forward-looking statements are subject to known and unknown risks,
uncertainties, assumptions and other factors that may cause our
actual results, performance or achievements to differ materially
and adversely from those anticipated or implied by our
forward-looking statements. Such risks, uncertainties, assumptions
and other factors include, but are not limited to: our ability to
continue to successfully commercialize DAYBUE, the timing,
enrollment and results of ongoing and future clinical trials and
our ability to continue to stay in compliance with applicable laws
and regulations. Given the risks and uncertainties, you should not
place undue reliance on these forward-looking statements. For a
discussion of these and other risks, uncertainties, assumptions and
other factors that may cause our actual results, performance or
achievements to differ, please refer to our quarterly report on
Form 10-Q for the period ended March 31, 2024 filed with the
Securities and Exchange Commission on May 9, 2024, as well as our
subsequent filings with the Securities and Exchange Commission from
time to time. The forward-looking statements contained herein are
made as of the date hereof, and we undertake no obligation to
update them after this date, except as required by law.
References 1 Acadia Pharmaceuticals Inc., Data on file. RTT US
Prevalence. March 2022. 2 Fu C, Armstrong D, Marsh E, et al.
Consensus guidelines on managing Rett syndrome across the lifespan.
BMJ Paediatrics Open. 2020; 4: 1-14. 3 Kyle SM, Vashi N, Justice
MJ. Rett syndrome: a neurological disorder with metabolic
components. Open Biol. 2018; 8: 170216. 4 Acadia Pharmaceuticals
Inc., Data on file. 5 Amir RE, Van den Veyver IB, Wan M, et al.
Rett syndrome is caused by mutations in X-linked MECP2, encoding
methyl-CpG-binding protein 2. Nat Genet. 1999; 23(2): 185-188. 6
Fukuda T, Itoh M, Ichikawa T, et al. Delayed maturation of neuronal
architecture and synaptogenesis in cerebral cortex of
Mecp2-deficient mice. J Neuropathol Exp Neurol. 2005; 64(6):
537-544. 7 Asaka Y, Jugloff DG, Zhang L, et al. Hippocampal
synaptic plasticity is impaired in the Mecp2-null mouse model of
Rett syndrome. Neurobiol Dis. 2006; 21(1): 217-227. 8 Neul JL,
Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic
criteria and nomenclature. Ann Neurol. 2010; 68(6): 944-950. 9
Daniel C, Tarquinio DO, Hou W, et al. The changing face of survival
in Rett syndrome and MECP2-related disorders. Pediatr Neurol. 2015;
53(5): 402-411. 10 Acadia Pharmaceuticals Inc., Data on file.
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Investor Contact: Acadia Pharmaceuticals Inc. Al Kildani (858)
261-2872 ir@acadia-pharm.com
Acadia Pharmaceuticals Inc. Jessica Tieszen (858) 261-2950
ir@acadia-pharm.com
Media Contact: Acadia Pharmaceuticals Inc. Deb Kazenelson (818)
395-3043 media@acadia-pharm.com
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