- Long-term data analysis suggests that REXULTI was associated
with a sustained, clinically meaningful response over 24 weeks with
a consistent rate of improvement.1
- Patients who received REXULTI showed a reduction in frequency
of the most common agitation behaviors compared to those who
received a placebo, including restlessness, pacing and
cursing.2
- Among the behaviors rated by caregivers as the “most
bothersome,” patients who received REXULTI had a greater reduction
in frequency of those behaviors compared to those who received a
placebo.3
- REXULTI is the first and only treatment approved by the U.S.
Food and Drug Administration (FDA) for agitation associated with
dementia due to Alzheimer’s disease.4
Otsuka Pharmaceutical Development & Commercialization, Inc.
(Otsuka) and Lundbeck Pharmaceuticals LLC (Lundbeck) presented new
post hoc pooled analyses of Phase 3 trials evaluating the safety
and efficacy of REXULTI® (brexpiprazole) in patients with agitation
associated with dementia due to Alzheimer’s disease.1-3 These data
analyses were presented in three posters at the 2024 Alzheimer’s
Association International Conference (AAIC), taking place July 28
to Aug. 2 in Philadelphia, USA.1-3
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New analysis from an extension trial confirmed the efficacy of
REXULTI in treating patients with agitation associated with
dementia due to Alzheimer’s disease. The analysis explored
clinically meaningful response (CMR) among patients over 12 and 24
weeks (NCT03548584 and NCT03594123), defined by a 20-point score
reduction from baseline in Cohen-Mansfield Agitation Inventory
(CMAI) total score. Over the initial 12-week Phase 3 trial period,
approximately 62 percent of patients who received REXULTI achieved
a CMR versus approximately 45 percent of patients who received
placebo. Following this, patients enrolled in a 12-week extension
trial, during which efficacy was an exploratory endpoint. Over the
full 24-week period, approximately 82 percent of patients
previously on REXULTI achieved a CMR while approximately 73 percent
of patients who were switched to REXULTI from placebo also achieved
a CMR.1
The second analysis focused specifically on patients (n=610) who
most frequently exhibited agitation symptoms at baseline in two
Phase 3 trials (NCT03548584 and NCT01862640). Efficacy was measured
using the CMAI, which gauges the frequency of 29 agitation
behaviors, including restlessness, pacing/aimless wandering, and
cursing or verbal aggression, each scoring 1 (never) to 7 (a few
times an hour). Patients taking REXULTI showed a reduction in
frequency of the most common agitation behaviors, with a
numerically greater reduction of the least squares mean CMAI score
in 24 out of the 29 agitation behaviors versus placebo from
baseline to Week 12.2
A further analysis of the same group of patients (n=610)
specifically examined the efficacy of REXULTI in agitation
behaviors that had been identified by unpaid caregivers as “most
bothersome” and which may influence their decision to transfer the
patient to long-term care. The survey highlighted agitation
behaviors such as excessive motor activity, verbal aggression and
physical aggression. In patients frequently exhibiting these
bothersome behaviors, fixed-dosed (2 or 3 mg/day) REXULTI was
associated with a greater reduction in frequency of these behaviors
than placebo.3
“Agitation is a complex and stressful aspect of caring for
people living with Alzheimer’s dementia,”5 said John Kraus, M.D.,
Ph.D., executive vice president and chief medical officer, Otsuka.
“This is the first time REXULTI was associated with a sustained
clinically meaningful response over 24 weeks, providing clinicians
with longer term data to inform clinical practice.”1
“These new data analyses underscore the efficacy of REXULTI in
addressing the most frequent forms of agitation behaviors in
patients,” said Johan Luthman, DDS, Ph.D., executive vice
president, Lundbeck Research & Development. “Collectively, the
analyses presented add to a substantial body of clinical evidence
showing the potential of REXULTI to address the many ways agitation
presents itself, which can impact patients’ and their caregivers’
lives.”
About Agitation Associated with Dementia Due to Alzheimer’s
Disease
Agitation associated with dementia due to Alzheimer’s disease is
a common neuropsychiatric symptom that is reported in approximately
half of all patients with dementia due to Alzheimer’s disease.5 The
condition has a large impact on patients, family members and
caregivers.5,6
Agitation associated with dementia due to Alzheimer’s disease
covers a large group of behaviors occurring in patients with this
condition, such as pacing, gesturing, profanity, shouting, shoving
and hitting.7 Symptoms of agitation are also a consistent predictor
of nursing home admission in patients with dementia, including
those with Alzheimer’s disease.8-9
About REXULTI (brexpiprazole)
Brexpiprazole was approved in the U.S. in 2015, as an adjunctive
therapy to antidepressants in adults with major depressive disorder
(MDD) and as a treatment for schizophrenia in adults. Most
recently, brexpiprazole was approved in the U.S. for the treatment
of agitation associated with dementia due to Alzheimer's disease,
in May 2023. Brexpiprazole was also approved by Health Canada for
schizophrenia and adjunctive treatment of MDD in 2017 and 2019,
respectively, and for agitation associated with dementia due to
Alzheimer's disease in 2024. It was approved by the European
Medicines Agency in 2018 for the treatment of schizophrenia and the
Ministry of Health, Labour and Welfare in Japan for the treatment
of schizophrenia and MDD in 2018 and 2023, respectively.
Brexpiprazole was discovered by Otsuka and is being co-developed
by Otsuka and Lundbeck. The mechanism of action of brexpiprazole is
unknown. Brexpiprazole has high receptor binding affinity to
norepinephrine, serotonin and dopamine receptors. It is an
antagonist at norepinephrine α1B and α2C receptors and serotonin
5-HT2A receptors, as well as a partial agonist at serotonin 5-HT1A
and dopamine D2 receptors.10-12
INDICATION and IMPORTANT SAFETY INFORMATION for
REXULTI® (brexpiprazole)
INDICATION: REXULTI is a prescription medicine used to
treat agitation that may happen with dementia due to Alzheimer’s
disease. REXULTI should not be used as an “as needed” treatment for
agitation that may happen with dementia due to Alzheimer’s
disease.
IMPORTANT SAFETY INFORMATION:
Increased risk of death in elderly
people with dementia-related psychosis. Medicines like REXULTI can
raise the risk of death in elderly people who have lost touch with
reality (psychosis) due to confusion and memory loss (dementia).
REXULTI is not approved for the treatment of people with
dementia-related psychosis without agitation that may happen with
dementia due to Alzheimer’s disease.
Do not take REXULTI if you are allergic to brexpiprazole
or any of the ingredients in REXULTI.
REXULTI may cause serious side effects, including:
- Cerebrovascular problems, including stroke, in elderly
people with dementia-related psychosis that can lead to
death.
- Neuroleptic malignant syndrome (NMS) is a serious condition
that can lead to death. Call your healthcare provider or go to
the nearest hospital emergency room right away if you have some or
all of the following signs and symptoms of NMS: high fever; changes
in your pulse, blood pressure, heart rate, and breathing; stiff
muscles; confusion; increased sweating.
- Uncontrolled body movements (tardive dyskinesia).
REXULTI may cause movements that you cannot control in your face,
tongue, or other body parts. Tardive dyskinesia may not go away,
even if you stop taking REXULTI. Tardive dyskinesia may also start
after you stop taking REXULTI.
- Problems with your metabolism such as:
- high blood sugar (hyperglycemia) and diabetes. Increases
in blood sugar can happen in some people who take REXULTI.
Extremely high blood sugar can lead to coma or death. Your
healthcare provider should check your blood sugar before you start,
or soon after you start REXULTI and then regularly during long term
treatment with REXULTI. Call your healthcare provider if you
have any of these symptoms of high blood sugar during treatment
with REXULTI:
- feel very thirsty
- feel very hungry
- feel sick to your stomach
- need to urinate more than usual
- feel weak or tired
- feel confused, or
- your breath smells fruity
- increased fat levels (cholesterol and triglycerides) in your
blood. Your healthcare provider should check the fat levels in
your blood before you start, or soon after you start REXULTI, and
then periodically during treatment with REXULTI.
- weight gain. You and your healthcare provider should
check your weight before you start and often during treatment with
REXULTI.
- Unusual and uncontrollable (compulsive) urges. Some
people taking REXULTI have had strong unusual urges to gamble and
gambling that cannot be controlled (compulsive gambling). Other
compulsive urges include sexual urges, shopping, and eating or
binge eating. If you or your family members notice that you are
having new or unusual strong urges or behaviors, talk to your
healthcare provider.
- Low white blood cell count. Your healthcare provider may
do blood tests during the first few months of treatment with
REXULTI.
- Decreased blood pressure (orthostatic hypotension) and
fainting. You may feel dizzy, lightheaded or pass out (faint)
when you rise too quickly from a sitting or lying position.
- Falls. REXULTI may make you sleepy or dizzy, may cause a
decrease in your blood pressure when changing position (orthostatic
hypotension), and can slow your thinking and motor skills which may
lead to falls that can cause fractures or other injuries.
- Seizures (convulsions).
- Problems controlling your body temperature so that you feel
too warm. Do not become too hot or dehydrated during treatment
with REXULTI. Do not exercise too much. In hot weather, stay inside
in a cool place if possible. Stay out of the sun. Do not wear too
much clothing or heavy clothing. Drink plenty of water.
- Difficulty swallowing that can cause food or liquid to
get into your lungs.
- Sleepiness, drowsiness, feeling tired, difficulty thinking
and doing normal activities. Do not drive a car, operate
machinery, or do other dangerous activities until you know how
REXULTI affects you. REXULTI may make you feel drowsy.
Before taking REXULTI, tell your healthcare provider about
all of your medical conditions, including if you:
- have or have had heart problems or a stroke
- have or have had low or high blood pressure
- have or have had diabetes or high blood sugar or a family
history of diabetes or high blood sugar.
- have or have had high levels of total cholesterol, LDL
cholesterol, or triglycerides, or low levels of HDL
cholesterol
- have or have had seizures (convulsions)
- have or have had kidney or liver problems
- have or have had a low white blood cell count
- are pregnant or plan to become pregnant. REXULTI may harm your
unborn baby. Taking REXULTI during your third trimester of
pregnancy may cause your baby to have abnormal muscle movements or
withdrawal symptoms after birth. Talk to your healthcare provider
about the risk to your unborn baby if you take REXULTI during
pregnancy.
- Tell your healthcare provider if you become pregnant or think
you are pregnant during treatment with REXULTI.
- There is a pregnancy exposure registry for women who are
exposed to REXULTI during pregnancy. If you become pregnant during
treatment with REXULTI, talk to your healthcare provider about
registering with the National Pregnancy Registry for Psychiatric
Medications. You can register by calling 1-866-961-2388 or visit
http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
- are breastfeeding or plan to breastfeed. It is not known if
REXULTI passes into your breast milk. Talk to your healthcare
provider about the best way to feed your baby during treatment with
REXULTI.
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. REXULTI and other medicines may
affect each other causing possible serious side effects. REXULTI
may affect the way other medicines work, and other medicines may
affect how REXULTI works. Your healthcare provider can tell you if
it is safe to take REXULTI with your other medicines. Do not start
or stop any medicines during treatment with REXULTI without first
talking to your healthcare provider.
The most common side effects of REXULTI include weight
gain, sleepiness, dizziness, common cold symptoms, and restlessness
or feeling like you need to move (akathisia).
These are not all the possible side effects of REXULTI. For more
information, ask your healthcare provider or pharmacist.
You are encouraged to report side effects of REXULTI
(brexpiprazole). Please contact Otsuka America Pharmaceutical, Inc.
at 1-800-438-9927 or FDA at 1-800-FDA-1088
(www.fda.gov/medwatch).
Please read FULL PRESCRIBING INFORMATION, including
BOXED WARNING, and MEDICATION GUIDE for REXULTI.
About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global
healthcare company with the corporate philosophy: Otsuka–people
creating new products for better health worldwide. Otsuka
researches, develops, manufactures, and markets innovative
products, with a focus on pharmaceutical products to meet unmet
medical needs and nutraceutical products for the maintenance of
everyday health.
In pharmaceuticals, Otsuka is a leader in the challenging areas
of mental, renal, and cardiovascular health and has additional
research programs in oncology and on several under-addressed
diseases including tuberculosis, a significant global public health
issue. These commitments illustrate how Otsuka is a “big venture”
company at heart, applying a youthful spirit of creativity in
everything it does.
Otsuka established a presence in the U.S. in 1973 and today its
U.S. affiliates include Otsuka Pharmaceutical Development &
Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical,
Inc. (OAPI). These two companies’ 2,250 employees in the U.S.
develop and commercialize medicines in the areas of mental health
and nephrology, using cutting-edge technology to address unmet
healthcare needs.
OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical
Co., Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd.
headquartered in Tokyo, Japan. The Otsuka group of companies
employed 34,400 people worldwide and had consolidated sales of
approximately USD 14.2 billion in 2023.
All Otsuka stories start by taking the road less traveled. Learn
more about Otsuka in the U.S. at www.otsuka-us.com and connect with
us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co.,
Ltd.’s global website is accessible at
https://www.otsuka.co.jp/en/.
About Lundbeck Lundbeck Pharmaceuticals LLC is a wholly
owned US subsidiary of H. Lundbeck A/S (HLUNa/ HLUNb, HLUNA
DC/HLUNB DC), a global biopharmaceutical company focused
exclusively on neuroscience, with more than 70 years of experience
in improving the lives of people with neurological and psychiatric
diseases.
As a focused innovator, we strive for our research and
development programs to tackle some of the most complex challenges.
We develop transformative medicines targeting people for whom there
are few, if any, treatment options. Our goal is to create long term
value and make a positive contribution to people and societies,
everywhere we operate. We are committed to fighting stigma and
discrimination, and we act to improve health equity for the people
we serve and the communities we are part of.
Too many people worldwide live with brain diseases – complex
conditions often invisible to others that nonetheless take a
tremendous toll on individuals, families and societies. We are
committed to fighting stigma and discrimination against people
living with brain diseases and advocating for broader social
acceptance of people with brain health conditions. Every day, we
strive for improved treatment and a better life for people living
with brain disease.
We have approximately 5,700 employees, and our products are
available in more than 100 countries. Our research programs tackle
some of the most complex challenges in neuroscience, and our
pipeline is focused on bringing forward transformative treatments
for brain diseases for which there are few, if any, therapeutic
options. We have research facilities in Denmark and the United
States, and our production facilities are located in Denmark,
France, and Italy.
Lundbeck US comprises the wholly owned US subsidiaries of
H. Lundbeck A/S, including Lundbeck LLC and
Lundbeck Pharmaceuticals LLC. With a workforce of more than
1,000 colleagues, Lundbeck US is deeply committed to
enhancing the lives of patients, families, and caregivers through
focused innovation in neuroscience. For additional information,
please visit Lundbeck.com/us and connect with us on LinkedIn and X
at @LundbeckUS.
References
- Brubaker M, Wang D, Chumki SR, et al. Sustained clinically
meaningful response in patients with agitation associated with
dementia due to Alzheimer’s disease treated with brexpiprazole:
post hoc analysis. Presented at AAIC (July 28–Aug. 2).
- Brubaker M, Wang D, Chumki SR, et al. Efficacy of brexpiprazole
on frequently occurring agitation behaviors in patients with
dementia due to Alzheimer’s disease: post hoc pooled analysis of
two randomized controlled trials. Presented at AAIC (July 28–Aug.
2).
- Brubaker M, Wang D, Chumki SR, et al. Efficacy of brexpiprazole
on agitation in patients with dementia due to Alzheimer’s disease
exhibiting behaviors most bothersome to caregivers: post hoc pooled
analysis of two randomized controlled trials. Presented at AAIC
(July 28–Aug. 2).
- FDA News Release. FDA Approves First Drug to Treat Agitation
Symptoms Associated with Dementia due to Alzheimer’s Disease.
Published: May 11, 2023. Last accessed: Feb. 20, 2024. Available
at:
https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-agitation-symptoms-associated-dementia-due-alzheimers-disease
- Halpern R, Seare J, Tong J, Hartry A, Olaoye A, Aigbogun MS.
Using electronic health records to estimate the prevalence of
agitation in Alzheimer disease/dementia. Int J Geriatr Psychiatry.
2019;34(3):420-431.
- Fillit H, Aigbogun MS, Gagnon-Sanschagrin P, et al. Impact of
agitation in long-term care residents with dementia in the United
States. Int J Geriatr Psychiatry. 2021;36(12):1959-1969.
- Sano M, Cummings J, Auer S, et al. Agitation in cognitive
disorders: Progress in the International Psychogeriatric
Association consensus clinical and research definition. Int
Psychogeriatr. 2024 April;36(4):238-250
- Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of
behavioral and psychological symptoms of dementia. BMJ.
2015;350:h369.
- Yaffe K, Fox P, Newcomer R, et al. Patient and caregiver
characteristics and nursing home placement in patients with
dementia. JAMA. 2002;287(16):2090-2097.
- Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: in vitro
and in vivo characterization of a novel serotonin-dopamine activity
modulator. J Pharmacol Exp Ther. 2014;350(3):589-604.
- Otsuka. Otsuka Pharmaceutical and Lundbeck Announce Topline
Results from Two Phase 3 Trials of Brexpiprazole as Combination
Therapy with Sertraline for the Treatment of Post-Traumatic Stress
Disorder in Adults. Release date: Sept. 07, 2023. Last accessed:
July 02, 2024. Available at:
https://www.otsuka-us.com/news/otsuka-pharmaceutical-and-lundbeck-announce-topline-results-two-phase-3-trials-brexpiprazole
- REXULTI® (brexpiprazole). Prescribing Information. FDA.
Reference ID: 4911319. May 2024.
© 2024 Otsuka America Pharmaceutical, Inc. All Rights Reserved
July 2024 11US24EBC0181
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Otsuka in the U.S. Robert Murphy Corporate Communications
Otsuka America Pharmaceutical, Inc. robert.murphy@otsuka-us.com +1
609 249 7262
Otsuka outside the U.S. Jeffrey Gilbert Leader,
Pharmaceutical PR Otsuka Pharmaceutical Co., Ltd.
Gilbert.jeffrey.a@otsuka.co.jp
Lundbeck in the U.S. Dyana Lescohier Corporate
Communications Lundbeck U.S. dyle@lundbeck.com +1 847 894 3586