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H. Lundbeck A — Earnings Release 2017
May 2, 2017
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Download source fileValby, Denmark, 2017-05-02 09:10 CEST (GLOBE NEWSWIRE) -- Valby, Denmark, 2 May
2017 - H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical Co., Ltd. (Otsuka)
announce top-line results from two phase III clinical trials evaluating the
efficacy, safety and tolerability of brexpiprazole in the treatment of
agitation in patients with dementia of the Alzheimer’s type.
The primary endpoint of both trials was change from baseline in the
Cohen-Mansfield Agitation Inventory (CMAI) total score, a 29-item scale to
systematically assess the symptoms of agitation[i]. The key secondary endpoint
was the change from baseline in the Clinical Global Impression-Severity of
Illness (CGI-S) score, a 7-point scale assessing overall severity of the
patient’s agitation. These studies were done in multiple countries in North
America and Europe, and in the Russian Federation.
In both studies, patients treated with brexpiprazole showed improvements in
symptoms of agitation relative to placebo. In the first study, the improvements
in the primary endpoint of CMAI for 2 mg brexpiprazole were statistically
better than placebo (p<0.05) and appeared more robust than the improvements on
the key secondary endpoint of CGI-S (p>0.05). In the second study, the
improvements in the primary endpoint of CMAI (p>0.05) appeared less robust than
the improvements on the key secondary endpoint of CGI-S (p<0.05). In both
studies, there was variability in the data from different countries, perhaps
associated with differing standards of care; the data from Russian sites showed
especially poor separation between placebo and drug.
Regarding safety and tolerability, both studies confirmed the profile of
brexpiprazole as observed in the clinical trials for schizophrenia and for
adjunctive treatment of major depressive disorder (MDD). The most common
adverse events in patients receiving brexpiprazole versus placebo (incidence
3% and greater than placebo) were insomnia (4.7% vs. 3.3%), agitation (3.5%
vs. 2.9%), and somnolence (3.3% vs. 2.2%). Overall mortality during the studies
was low (0.86%) and none of the deaths were considered to be related to
treatment.
About the studies
Both trials were randomized, double-blind, placebo-controlled phase III studies
that enrolled a total of approximately 700 participants. Trial participants
were between 51 and 90 years of age with a diagnosis of probable Alzheimer’s
disease and symptoms of agitation. Both outpatients and patients living in
institutional care settings were included in the trials. One of the trials
studied fixed doses of either 1 or 2 mg per day of brexpiprazole or placebo,
while the other trial studied a flexible dose range of 0.5 mg, 1 mg or 2 mg per
day of brexpiprazole, or placebo. Both trials were 12 weeks in duration.
The companies plan to meet with the U.S. Food and Drug Administration (FDA) to
discuss the results of the studies. The results will be presented in scientific
congresses over the course of the next year.
About Alzheimer’s disease and related agitation
Alzheimer’s disease is estimated to account for between 60 and 80% of the
estimated 5.5 million people in the U.S. with dementia[ii]. Behavioral symptoms
develop in the majority of people with Alzheimer's disease and many of these
symptoms are clinically diagnosed as “agitation,” including wandering,
restlessness, significant emotional distress, aggressive behaviors, and
irritability. Symptoms of agitation place a serious burden on the people
afflicted with the disease and their caregivers, significantly affecting the
quality of life for all concerned. Agitation is often a determining factor in
the decision to place patients in high-level residential care facilities,
contributing to the roughly USD 259 billion cost burden of Alzheimer’s disease
in the U.S. for 2017. It is estimated that agitation symptoms affect nearly 50%
or more of patients with Alzheimer’s disease observed over a multiyear
period[iii].
About brexpiprazole
Brexpiprazole was approved by the U.S. Food and Drug Administration in July
2015 to treat patients with schizophrenia and as an adjunctive treatment for
patients with major depressive disorder (MDD). Brexpiprazole was also approved
in February 2017 by Health Canada for the treatment of schizophrenia. In both
countries brexpiprazole is distributed and marketed under the brand name
Rexulti®.
Brexpiprazole is discovered by Otsuka and co-developed by Otsuka and Lundbeck.
The mechanism of action for brexpiprazole in the adjunctive treatment of major
depressive disorder or schizophrenia is unknown. However, the efficacy of
brexpiprazole may be mediated through a combination of partial agonist activity
at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at
serotonin 5-HT2A receptors. Brexpiprazole exhibits high affinity
(sub-nanomolar) for these receptors as well as for noradrenaline alpha1B/2C
receptors.
INDICATIONS and IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole)
INDICATIONS
REXULTI is indicated for:
• Use as an adjunctive therapy to antidepressants in adults with
major depressive disorder
• Treatment of schizophrenia in adults
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 increased risk of death. REXULTI is not approved for the treatment
of patients with dementia-related psychosis.
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
Antidepressants increase the risk of suicidal thoughts and behaviors in
patients aged 24 years and younger. Monitor for clinical worsening and
emergence of suicidal thoughts and behaviors. The safety and effectiveness of
REXULTI have not been established in pediatric patients.
Contraindication: In patients with known hypersensitivity reaction to
brexpiprazole or any of its components. Reactions have included: rash, facial
swelling, urticaria and anaphylaxis.
Cerebrovascular Adverse Events, Including Stroke: In clinical trials, elderly
patients with dementia randomized to risperidone, aripiprazole, and olanzapine
had a higher incidence of stroke and transient ischemic attack, including fatal
stroke. REXULTI is not approved for the treatment of patients with
dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom
complex reported in association with administration of antipsychotic drugs.
Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status
and evidence of autonomic instability. Additional signs may include elevated
creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal
failure. Manage NMS with immediate discontinuation of REXULTI, intensive
symptomatic treatment, and monitoring.
Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible,
are believed to increase with duration of treatment and total cumulative dose
of antipsychotic drugs. TD can develop after a relatively brief treatment
period, even at low doses, or after discontinuation of treatment. For chronic
treatment, use the lowest dose and shortest duration of REXULTI needed to
produce a clinical response. If signs and symptoms of TD appear, drug
discontinuation should be considered.
Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes
including:
• Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases
extreme and associated with ketoacidosis or hyperosmolar coma or death, has
been reported in patients treated with atypical antipsychotics. Assess fasting
plasma glucose before or soon after initiation of antipsychotic medication, and
monitor periodically during long-term treatment.
• Dyslipidemia: Atypical antipsychotics cause adverse alterations
in lipids. Before or soon after initiation of antipsychotic medication, obtain
a fasting lipid profile at baseline and monitor periodically during treatment.
• Weight Gain: Weight gain has been observed in patients treated
with REXULTI. Monitor weight at baseline and frequently thereafter.
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia and neutropenia have
been reported with antipsychotics. Agranulocytosis (including fatal cases) has
been reported with other agents in this class. Monitor complete blood count in
patients with pre-existing low white blood cell count (WBC)/absolute neutrophil
count or history of drug-induced leukopenia/neutropenia. Discontinue REXULTI at
the first sign of a clinically significant decline in WBC and in severely
neutropenic patients.
Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic
hypotension and syncope. Generally, the risk is greatest during initial dose
titration and when increasing the dose. Monitor in patients vulnerable to
hypotension, and those with cardiovascular and cerebrovascular diseases.
Falls: Antipsychotics may cause somnolence, postural hypotension, motor and
sensory instability, which may lead to falls causing fractures or other
injuries. For patients with diseases, conditions, or medications that could
exacerbate these effects, complete fall risk assessments when initiating
treatment and recurrently during therapy.
Seizures: REXULTI may cause seizures and should be used with caution in
patients with a history of seizures or with conditions that lower the seizure
threshold.
Body Temperature Dysregulation: Use REXULTI with caution in patients who may
experience conditions that increase body temperature (e.g., strenuous exercise,
extreme heat, dehydration, or concomitant use with anticholinergics).
Dysphagia: Esophageal dysmotility and aspiration have been associated with
antipsychotics, including REXULTI, and should be used with caution in patients
at risk for aspiration.
Potential for Cognitive and Motor Impairment: REXULTI has the potential to
impair judgment, thinking, or motor skills. Patients should not drive or
operate hazardous machinery until they are reasonably certain REXULTI does not
affect them adversely.
Concomitant Medication: Dosage adjustments are recommended in patients who are
known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking
concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers.
Most commonly observed adverse reactions: In clinical trials, the most common
adverse reactions were:
• Major Depressive Disorder (MDD) (adjunctive treatment to
antidepressant therapy; ?5% incidence and at least twice the rate of placebo
for REXULTI vs. placebo, respectively): akathisia (9% vs. 2%) and weight
increase (7% vs. 2%)
• Schizophrenia (?4% incidence and twice incidence of placebo for
REXULTI vs. placebo, respectively): weight increased (4% vs. 2%)
Dystonia: Symptoms of dystonia may occur in susceptible individuals during the
first days of treatment and at low doses.
Pregnancy: Adequate and well-controlled studies to assess the risks of REXULTI
during pregnancy have not been conducted. REXULTI should be used during
pregnancy only if the benefit justifies the risk to the fetus.
Lactation: It is not known if REXULTI is excreted in human breast milk. A
decision should be made whether to discontinue nursing or to discontinue the
drug, taking into account the importance of the drug to the mother.
To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical,
Inc. at 1-800- 438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).
Please see accompanying FULL PRESCRIBING INFORMATION, including BOXED WARNING.
Lundbeck contacts
Investors: Media:
Palle Holm Olesen Mads Kronborg
Vice President, Investor Relations Senior Director, Corp. Communication
[email protected] [email protected]
+45 30 83 24 26 +45 36 43 40 00
USA:
Nick Przybyciel
Public Relations Manager
[email protected]
+1 847-527-9976
Otsuka Contacts
Media:
Outside U.S. U.S.
Jeffrey Gilbert Kimberly Whitefield
Leader, Pharmaceutical PR Corporate Communications
Otsuka Pharmaceutical Co, Ltd. Otsuka America Pharmaceutical, Inc.
[email protected] [email protected]
+81 3 6361 7379, +81 80 8728 6039 +1 609 535-9259
Investors:
Yoko Ishii
Otsuka Holdings Co., Ltd.
[email protected]
+81 3 6361 7411
About H. Lundbeck A/S
H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global pharmaceutical company
specialized in psychiatric and neurological disorders. For more than 70 years,
we have been at the forefront of research within neuroscience. Our key areas of
focus are Alzheimer's disease, depression, Parkinson's disease and
schizophrenia.
Our approximately 5,000 employees in 55 countries are engaged in the entire
value chain throughout research, development, manufacturing, marketing and
sales. Our pipeline consists of several late-stage development programmes and
our products are available in more than 100 countries. We have production
facilities in Denmark, France and Italy. Lundbeck generated revenue of DKK 15.6
billion in 2016 (EUR 2.1 billion; USD 2.2 billion).
For additional information, we encourage you to visit our corporate site
www.lundbeck.com and connect with us on Twitter at @Lundbeck.
About Otsuka Pharmaceutical Co., Ltd.
Otsuka Pharmaceutical 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 for the treatment of diseases and
nutraceutical products for the maintenance of everyday health.
In pharmaceuticals, Otsuka is a leader in the challenging area of mental health
and also has research programs 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 Pharmaceutical is a subsidiary of Otsuka Holdings Co., Ltd.
headquartered in Tokyo, Japan. The Otsuka group of companies employed 45,000
people worldwide and had consolidated sales of approximately USD 11 billion
(EUR 9.9 billion) in 2016.
All Otsuka stories start by taking the road less travelled. Learn more about
Otsuka Pharmaceutical Company on its global website at
https://www.otsuka.co.jp/en. Learn more about Otsuka in the U.S. at
www.otsuka-us.com and connect with us on Twitter at @OtsukaUS.
Safe Harbor/Forward-Looking Statements
The above information contains forward-looking statements that provide our
expectations or forecasts of future events such as new product introductions,
product approvals and financial performance.
Such forward-looking statements are subject to risks, uncertainties and
inaccurate assumptions. This may cause actual results to differ materially from
expectations and it may cause any or all of our forward-looking statements here
or in other publications to be wrong. Factors that may affect future results
include interest rate and currency exchange rate fluctuations, delay or failure
of development projects, production problems, unexpected contract breaches or
terminations, government-mandated or market-driven price decreases for
Lundbeck's products, introduction of competing products, Lundbeck's ability to
successfully market both new and existing products, exposure to product
liability and other lawsuits, changes in reimbursement rules and governmental
laws and related interpretation thereof, and unexpected growth in costs and
expenses.
Certain assumptions made by Lundbeck are required by Danish Securities Law for
full disclosure of material corporate information. Some assumptions, including
assumptions relating to sales associated with product that is prescribed for
unapproved uses, are made taking into account past performances of other
similar drugs for similar disease states or past performance of the same drug
in other regions where the product is currently marketed. It is important to
note that although physicians may, as part of their freedom to practice
medicine in the US, prescribe approved drugs for any use they deem appropriate,
including unapproved uses, at Lundbeck, promotion of unapproved uses is
strictly prohibited.
[i] Garriga M., Pacchiarotti, I., Kasper, S., Zeller S. et al. Assessment and
management of agitation in psychiatry: Expert consensus. World J Biological
Psychiatry 2016;17,(2):93
[ii] Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. 2017;
13:325-373
[iii]Bergh, S.and Selbæk, G. The prevalence and the course of neuropsychiatric
symptoms in patients with dementia. Norsk Epidemiologi 2012; 22 (2): 225-232.