- The study did not achieve statistical
significance on the primary endpoint
- Conference call and webcast to be held today
at 4:30 p.m. Eastern Time
ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD) today announced
top-line results from its 298 patient Phase 3 CLARITY study which
combined two identical, double-blind, placebo-controlled studies
evaluating the efficacy, safety and tolerability of pimavanserin as
an adjunctive treatment for major depressive disorder (MDD). The
combined efficacy and safety analysis was pre-specified prior to
data unblinding following feedback from the FDA.
The study did not achieve statistical significance on the
primary endpoint which was the 17-item Hamilton Depression Rating
Scale (HAMD-17) total score change from baseline to week 5.
Pimavanserin 34 mg, given once-daily as an adjunctive treatment to
standard antidepressant therapy was associated with a mean
reduction of 9.0 in HAMD-17 total score compared to 8.1 for placebo
as an adjunctive treatment (p=0.296).
Positive results were observed on the key secondary endpoint,
the Clinical Global Impression – Severity (CGI-S) score, a
clinician assessment of a patient’s severity of depression (nominal
p=0.042).
“We observed a consistent improvement of depressive symptoms
over time with pimavanserin but, unfortunately, the robust positive
results from our CLARITY-1 study were not replicated,” said Serge
Stankovic, ACADIA’s President. “While these results do not support
the product profile to pursue an additional Phase 3 study in
adjunctive MDD, we will continue to analyze the data and the
findings from our earlier positive depression studies as we assess
next steps. All of us at ACADIA thank the patients, their families
and the investigators who participated in the Phase 3 CLARITY
study.”
In the study, pimavanserin was generally well-tolerated when
added to existing antidepressant therapy, and similar rates of
adverse events were observed between pimavanserin (58.1%) and
placebo (54.7%).
About the Phase 3 CLARITY Study
The Phase 3 CLARITY study is a combination of CLARITY-2 and
CLARITY-3, which were both 6-week, parallel-designed, randomized,
double-blind, placebo-controlled, multi-center studies designed to
evaluate the efficacy and safety of pimavanserin as adjunctive
treatment in patients with MDD who have an inadequate response to
standard antidepressant therapy with either a selective serotonin
reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake
inhibitor (SNRI). A total of 298 patients were randomized to
receive six weeks of oral treatment with either 34 mg of
pimavanserin or placebo, once daily, in addition to their ongoing
antidepressant. The primary endpoint was change from baseline on
the HAMD-17 total score.
Phase 3 CLARITY Study Results:
Efficacy Analysis
- Statistical significance not achieved on the primary endpoint:
HAMD-17 (p=0.296).
- Positive results observed on key secondary endpoint: CGI-S
(nominal p=0.042).
- Positive results observed on Karolinska Sleepiness Scale (KSS)
score (nominal p=0.005).
- Clinically meaningful separation was not achieved on the other
secondary endpoints.
Safety and Tolerability
- Similar rates of adverse events were observed between
pimavanserin (58.1%) and placebo (54.7%).
- Adverse events reported in greater than 5% of patients on
pimavanserin and greater than placebo were diarrhea, dry mouth and
headache.
- Discontinuations due to adverse events were 2.7% for both
pimavanserin and placebo.
- Two subjects in each of the pimavanserin and placebo groups
reported serious adverse events (SAEs). These SAEs were deemed not
to be related to the study drug by the investigators.
- The adjunctive use of pimavanserin did not result in clinically
significant differences in vital signs, metabolic parameters or
extrapyramidal symptoms compared to placebo.
ACADIA previously announced plans to combine its CLARITY-2 and
CLARITY-3 Phase 3 studies evaluating pimavanserin for the
adjunctive treatment of MDD with a pre-specified statistical
analysis plan. The two Phase 3 studies concluded with slightly more
than 50% enrollment.
Patients who completed the Phase 3 study were eligible to
participate in the ongoing 52-week open-label extension study to
evaluate the long-term safety and tolerability of pimavanserin as
adjunctive treatment to standard antidepressants in MDD.
About the CLARITY-1 Study
CLARITY-1 was a Phase 2, 10-week, randomized, double-blind,
placebo-controlled, multi-center, 2-stage sequential parallel
comparison design (SPCD) study that evaluated the safety,
tolerability, and efficacy of pimavanserin (34 mg once daily) as an
adjunctive treatment in patients with MDD who had an inadequate
response to a stable dose of standard antidepressant therapy with
either a SSRI or a SNRI. The study was conducted in collaboration
with the Massachusetts General Hospital Clinical Trials Network
& Institute and randomized 207 patients across 27 clinical
research centers in the U.S. and was completed in 2018.
In the trial, pimavanserin met the primary endpoint by
significantly reducing the HAMD-17 total score compared to placebo
(p=0.039). On the key secondary endpoint, pimavanserin demonstrated
statistically significant reductions compared to placebo in the
Sheehan Disability Scale score (p=0.004). Positive results were
also observed for seven other secondary endpoints including the
CGI-S score (p=0.008) and the KSS score (p=0.021).
In the parallel design portion (Stage 1) of this SPCD study,
adding pimavanserin to SSRI or SNRI therapy also significantly
reduced HAMD-17 scores compared to placebo (p=0.0003). On the key
secondary endpoint, pimavanserin also demonstrated statistically
significant reductions compared to placebo in the Sheehan
Disability Scale score (p=0.004).
About the Open-Label Comorbid Parkinson’s Disease and Depression
Study
This was an 8-week, open-label, single-arm Phase 2 study
evaluating the efficacy and safety of pimavanserin as an adjunct to
a SSRI or a SNRI or as a monotherapy in adults with both
Parkinson’s disease and depression (n=47) and was completed in
2019. In the study, patients treated with pimavanserin had
significant improvement on the primary endpoint, the HAMD-17 total
score change in baseline to week 8 (p<0.0001), with significant
improvement seen as early as week 2 (p<0.0001). Improvement of
≥50% on the HAMD-17 total score was observed in 60.0% of patients
at week 8, with 44.4% of patients reaching remission (HAMD-17
≤7).
Additional results from this study showed that Parkinson’s
disease patients treated with pimavanserin for depression also
demonstrated improvement on multiple secondary endpoints compared
to baseline, including the CGI-S score (p<0.0001) and the
SCOPA-Global Sleep Quality scale (p<0.0001).
Conference Call and Webcast Information
ACADIA will provide a corporate update via conference call and
webcast today at 4:30 p.m. Eastern Time. The conference call can be
accessed by dialing 855-638-4820 for participants in the U.S. or
Canada and 443-877-4067 for international callers (reference
passcode 1486597). A telephone replay of the conference call may be
accessed through July 27, 2020 by dialing 855-859-2056 for callers
in the U.S. or Canada and 404-537-3406 for international callers
(reference passcode 1486597). The conference call will also be
webcast live on ACADIA’s website, www.acadia-pharm.com, in the
investors section and will be archived there until August 20,
2020.
About Major Depressive Disorder
According to the National Institute of Mental Health, MDD
affects approximately 17 million adults in the U.S.1, with
approximately 2.5 million adults treated with adjunctive
therapy.2,3 MDD is a condition characterized by depressive symptoms
such as a depressed mood or a loss of interest or pleasure in daily
activities for more than two weeks, as well as impaired social,
occupational, or other important functioning. Continuing depression
has been consistently linked with greater economic burden, with
higher rate of healthcare utilization and reduced work
productivity.4 The majority of people who suffer from MDD do not
respond adequately to initial antidepressant therapy or discontinue
due to side effects or safety concerns.5,6
About Pimavanserin
Pimavanserin is a selective serotonin inverse agonist and
antagonist preferentially targeting 5-HT2A receptors. The serotonin
system is thought to play an important role in neuropsychiatric
disorders. In vitro, pimavanserin demonstrated no appreciable
binding affinity for dopamine (including D2), histamine,
muscarinic, or adrenergic receptors. Pimavanserin was approved for
the treatment of hallucinations and delusions associated with
Parkinson’s disease psychosis by the U.S. Food and Drug
Administration in April 2016 under the trade name NUPLAZID®. ACADIA
submitted a supplemental new drug application (sNDA) for
pimavanserin for the treatment of hallucinations and delusions
associated with dementia-related psychosis on June 3, 2020. The FDA
has accepted for filing the sNDA for DRP with a PDUFA date of April
3, 2021. NUPLAZID is not approved for dementia-related psychosis.
In addition, ACADIA is developing pimavanserin in other
neuropsychiatric conditions.
About ACADIA Pharmaceuticals
ACADIA is a biopharmaceutical company focused on the development
and commercialization of innovative medicines to address unmet
medical needs in central nervous system disorders. ACADIA has
developed and commercialized the first and only medicine approved
for the treatment of hallucinations and delusions associated with
Parkinson’s disease psychosis. ACADIA’s development efforts are
focused on pimavanserin for additional neuropsychiatric conditions,
trofinetide for Rett syndrome, and an early-stage muscarinic
receptor program. This press release and further information about
ACADIA can be found at: www.acadia-pharm.com.
Forward-Looking Statements
Statements in this press release that are not strictly
historical in nature are forward-looking statements. These
statements include, but are not limited to, statements related to
the potential benefits of pimavanserin as adjunctive treatment for
major depressive disorder or other central nervous system disorders
as well as the potential results of clinical trials of pimavanserin
in other indications. These statements are only predictions based
on current information and expectations and involve a number of
risks and uncertainties. Actual events or results may differ
materially from those projected in any of such statements due to
various factors, including the risks and uncertainties inherent in
drug development, approval and commercialization, and the fact that
past results of clinical trials may not be indicative of future
trial results. For a discussion of these and other factors, please
refer to ACADIA’s annual report on Form 10-K for the year ended
December 31, 2019 as well as ACADIA’s subsequent filings with the
Securities and Exchange Commission. You are cautioned not to place
undue reliance on these forward-looking statements, which speak
only as of the date hereof. This caution is made under the safe
harbor provisions of the Private Securities Litigation Reform Act
of 1995. All forward-looking statements are qualified in their
entirety by this cautionary statement and ACADIA undertakes no
obligation to revise or update this press release to reflect events
or circumstances after the date hereof, except as required by
law.
Important Safety Information and Indication for NUPLAZID
(pimavanserin)
Indication
NUPLAZID is indicated for the treatment of hallucinations and
delusions associated with Parkinson’s disease psychosis.
Important Safety Information
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH
DEMENTIA-RELATED PSYCHOSIS
- Elderly patients with dementia-related psychosis treated
with antipsychotic drugs are at an increased risk of
death.
- NUPLAZID is not approved for the treatment of patients with
dementia-related psychosis unrelated to the hallucinations and
delusions associated with Parkinson’s disease psychosis.
- Contraindication: NUPLAZID is contraindicated in
patients with a history of a hypersensitivity reaction to
pimavanserin or any of its components. Rash, urticaria, and
reactions consistent with angioedema (e.g., tongue swelling,
circumoral edema, throat tightness, and dyspnea) have been
reported.
- Warnings and Precautions: QT Interval Prolongation
- NUPLAZID prolongs the QT interval. The use of NUPLAZID should
be avoided in patients with known QT prolongation or in combination
with other drugs known to prolong QT interval including Class 1A
antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic
medications, and certain antibiotics.
- NUPLAZID should also be avoided in patients with a history of
cardiac arrhythmias, as well as other circumstances that may
increase the risk of the occurrence of torsade de pointes and/or
sudden death, including symptomatic bradycardia, hypokalemia or
hypomagnesemia, and presence of congenital prolongation of the QT
interval.
- Adverse Reactions: The common adverse reactions (≥2% for
NUPLAZID and greater than placebo) were peripheral edema (7% vs
2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination
(5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs
<1%).
- Drug Interactions:
- Coadministration with strong CYP3A4 inhibitors (e.g.,
ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to
10 mg taken orally as one tablet once daily.
- Coadministration with strong or moderate CYP3A4 inducers
reduces NUPLAZID exposure. Avoid concomitant use of strong or
moderate CYP3A4 inducers with NUPLAZID.
Dosage and Administration Recommended dose: 34 mg capsule
taken orally once daily, without titration.
NUPLAZID is available as 34 mg capsules and 10 mg tablets.
Please read the full Prescribing Information including Boxed
WARNING.
References
1National Institute of Mental Health. (2017). Major Depression.
Retrieved from
http://www.nimh.nih.gov/health/statistics/major-depression.shtml
2IMS NSP, NPA, NDTI MAT-24 month data through Aug 2017. 3PLOS One,
Characterization of Treatment Resistant Depression Episodes in a
Cohort of Patients from a US Commercial Claims Database, Oct 2013,
Vol 8, Issue 10. 4Greenberg PE, Fournier AA, Sisitsky T, Pike CT,
Kessler RC. The economic burden of adults with major depressive
disorder in the United States (2005 and 2010). J Clin Psych.
2015;76(2):155-162. doi: 10.4088/JCP.14m09298. 5Rush AJ, et al.
(2007) Am J. Psychiatry 163:11, pp. 1905-1917 (STAR*D Study).
6Sansone RA, Sansone LA. Antidepressant adherence: are patients
taking their medications? Innov Clin Neurosci.
2012;9(5-6):41-46.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200720005747/en/
Media Contact: ACADIA Pharmaceuticals Inc. Stephanie Fagan (858)
212-0534 media@acadia-pharm.com
Investor Contact: ACADIA Pharmaceuticals Inc. Mark Johnson, CFA
(858) 261-2771 ir@acadia-pharm.com
Acadia Pharmaceuticals (NASDAQ:ACAD)
Historical Stock Chart
From Mar 2024 to Apr 2024
Acadia Pharmaceuticals (NASDAQ:ACAD)
Historical Stock Chart
From Apr 2023 to Apr 2024