NUEDEXTA® Effective for Pseudobulbar Affect (PBA) in Patients with Alzheimer's Disease and other Dementias, Stroke and Traumatic Brain Injury

ALISO VIEJO, Calif., June 8, 2016 /PRNewswire/ -- Avanir Pharmaceuticals, Inc. today announced the publication of full results from the PRISM II study, which demonstrated significant improvement of pseudobulbar affect (PBA) following treatment with NUEDEXTA^® (dextromethorphan hydrobromide/quinidine sulfate) capsules in patients with Alzheimer's disease (AD) and other dementias, stroke and traumatic brain injury (TBI). The study was published online in BMC Neurology.

PBA is a condition characterized by sudden and uncontrollable outbursts of crying and/or laughing resulting from certain neurologic diseases or brain injury. NUEDEXTA is the only pharmaceutical agent approved by the U.S. Food and Drug Administration for the treatment of PBA. With the PRISM II data, NUEDEXTA has now been studied in five of the most common neurologic illnesses where PBA symptoms are present -- amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease; multiple sclerosis (MS); AD and other dementias; stroke and TBI.

"Pseudobulbar affect, or PBA, can be very distressing for people with a variety of neurologic conditions, since the crying or laughing outbursts associated with the condition can be contrary or exaggerated to their inner mood state," said Flora M. Hammond, MD, lead investigator and chief of medical affairs, Indiana University School of Medicine. "In this study, NUEDEXTA significantly reduced these PBA crying or laughing episodes in individuals with dementia, stroke or traumatic brain injury from an average of 12 per week at baseline to two per week at the 90-day endpoint, and the treatment was well-tolerated overall."

PRISM II was an open-label, multicenter study that included 367 participants who received NUEDEXTA for 90 days. Results included:

• Center for Neurologic Study–Lability Scale (CNS-LS) score improved significantly from a mean of 20.5 at baseline to 12.8 (P<.001) at the 90-day endpoint, which is consistent with results seen with NUEDEXTA in the Phase III trial. The CNS-LS is a seven-item rating scale measure of PBA episode frequency and severity.
• PBA episodes were reduced by 72.6% (P<.001) compared to baseline at the 90-day endpoint. PBA episode counts over the seven days prior to study visit decreased from a median of 12 at baseline to two at the 90-day endpoint; 35.5% of patients experienced no PBA episodes at the 90-day endpoint.
• Clinicians rated 77% of patients as "very much improved" or "much improved" with respect to PBA symptoms, as did 72% of participants (or caregivers) using the Clinical Global Impression of Change (CGI-C) and Patient (or Caregiver) Global Impression of Change (PGI-C) respectively. The CGI-C and PGI-C are seven-point scales to assess overall change in the patient's condition with respect to PBA.

"This study adds to the body of evidence demonstrating the safety and efficacy of NUEDEXTA for patients with PBA," said Sanjay Dubé, MD, vice president clinical development R&D at Avanir. "We now have safety and efficacy data for NUEDEXTA in five of the most common neurologic illnesses where PBA symptoms are present -- ALS, MS, AD and other dementias, stroke and TBI."

The adverse event (AE) profile in PRISM II was consistent with the known safety profile of NUEDEXTA. The most frequently occurring AEs were diarrhea (5.4%), headache (4.1%), urinary tract infection (2.7%) and dizziness (2.5%); 9.8% of patients had AEs that led to discontinuation. Serious AEs were reported in 6.3% of patients; however, none were considered to be related to NUEDEXTA treatment. 

About PRISM II
PRISM II was designed to evaluate the safety, tolerability and effectiveness of NUEDEXTA capsules containing 20 mg dextromethorphan hydrobromide (DM) and 10 mg quinidine sulfate (Q) for treatment of PBA in patients with dementia of the Alzheimer's type (AD) and other dementias, stroke and traumatic brain injury (TBI). The nationwide, open-label study enrolled 367 patients at 74 study centers. Eligible patients were age ≥18 years with a clinical diagnosis of PBA and baseline score ≥13 on the CNS-LS. Patients with TBI due to a penetrating head injury were excluded. Patients on stable medications, including psychiatric medications, were eligible for the study provided they were not contraindicated for use with NUEDEXTA; the majority of patients (70.8%) were using one or more psychiatric medications, most commonly antidepressants (48.5%), at baseline.

Patients were treated with NUEDEXTA for 12 weeks (once daily in week one, followed by twice daily for the remainder of the study). The primary endpoint was change from baseline in PBA symptoms as measured by the CNS-LS, an instrument originally validated as a measure of PBA episode frequency and severity in patients with ALS and MS. Determination of effectiveness was based on a comparison of CNS-LS change in PRISM II with that seen for NUEDEXTA and placebo in a previously completed pivotal Phase III study, as well as safety/tolerability and other patient outcomes when used under usual conditions in patients with dementia, stroke or TBI. Additional outcomes measures included number of weekly PBA episodes (crying and/or laughing); Mini-Mental State Examination; PBA impact on quality of life; CGIC; PGIC; patients' satisfaction with treatment; Patient Health Questionnaire (PHQ-9) (to evaluate mood symptoms); and a functional measure consisting of the Neurobehavioral Functioning Inventory for patients with TBI and Stroke Impact Scale for patients with stroke. Safety measures included monitoring of adverse events, concomitant medication usage and vital signs.

About Pseudobulbar Affect (PBA)
PBA is a neurologic condition characterized by involuntary, sudden and frequent episodes of crying and/or laughing that are often contrary or exaggerated to the patient's inner mood state. PBA occurs secondary to a variety of neurologic conditions such as traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, stroke and Alzheimer's disease. When these disorders damage areas of the brain that regulate normal emotional expression, they can lead to uncontrollable episodes of crying or laughing. For more information about PBA, visit www.PBAFacts.com.

About NUEDEXTA
NUEDEXTA is an innovative combination of two well-characterized components, dextromethorphan hydrobromide, the ingredient active in the central nervous system, and quinidine sulfate, a metabolic inhibitor enabling therapeutic concentrations of dextromethorphan. Dextromethorphan acts on sigma-1 and NMDA receptors in the brain, although the mechanism by which NUEDEXTA exerts therapeutic effects in patients with PBA is unknown.

NUEDEXTA Important Safety Information
NUEDEXTA is indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of otherwise unrelated neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of crying and/or laughing. PBA episodes typically occur out of proportion or incongruent to the underlying emotional state. PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurological disease or injury.

NUEDEXTA (dextromethorphan hydrobromide and quinidine sulfate) capsules 20 mg/10 mg can interact with other medications, including those metabolized by CYP2D6, causing significant changes in blood levels of those medications and/or NUEDEXTA which may lead to serious side effects. Adjust dose of the other medication or use alternate treatment when clinically indicated.

NUEDEXTA is contraindicated in patients concomitantly taking: QT-prolonging drugs metabolized by CYP2D6 (e.g., thioridazine and pimozide); monoamine oxidase inhibitors (MAOIs) within the preceding or following 14 days; other drugs containing quinidine, quinine, or mefloquine and in patients with a known hypersensitivity (including prior quinidine-induced thrombocytopenia, hepatitis, bone-marrow depression, or lupus-like syndrome) to these drugs or any of NUEDEXTA's components.

NUEDEXTA is contraindicated in patients with certain risk factors for arrhythmia such as: Prolonged QT interval; congenital long QT syndrome, history suggestive of torsades de pointes; heart failure; complete atrioventricular (AV) block or risk of AV block without an implanted pacemaker.

NUEDEXTA causes dose-dependent QTc prolongation. When initiating NUEDEXTA in patients at risk for QT prolongation and torsades de pointes, electrocardiographic (ECG) evaluation should be conducted at baseline and 3-4 hours after the first dose. Risk factors include left ventricular hypertrophy or dystrophy or concomitant use of drugs that prolong QT interval or concurrent use of moderate to strong CYP3A4 inhibitors.

Quinidine can cause immune-mediated thrombocytopenia that can be severe or fatal. Discontinue use of NUEDEXTA if thrombocytopenia, hepatitis, serotonin syndrome or a hypersensitivity reaction occurs. Anticholinergic effects have been reported in patients taking quinidine. Monitor for worsening in myasthenia gravis.

NUEDEXTA may cause dizziness. Precautions to reduce the risk of falls should be taken, particularly for patients with motor impairment affecting gait or a history of falls.

The most common adverse reactions are diarrhea, dizziness, cough, vomiting, asthenia, peripheral edema, urinary tract infection, influenza, increased gamma-glutamyltransferase, and flatulence.

These are not all the risks from use of NUEDEXTA.

Please refer to the Full Prescribing Information or visit www.NUEDEXTA.com.

About Avanir Pharmaceuticals, Inc.
Avanir Pharmaceuticals, Inc. is a biopharmaceutical company focused on bringing innovative medicines to patients with central nervous system disorders of high unmet medical need. As part of our commitment, we have extensively invested in our pipeline and are dedicated to advancing medicines that can substantially improve the lives of patients and their loved ones. For more information about Avanir, please visit http://www.avanir.com.

Avanir is a subsidiary of Otsuka America, Inc. (OAI), a holding company established in the U.S. in 1989. OAI is wholly owned by Otsuka Pharmaceutical Co., Ltd., a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' 

Otsuka researches, develops, manufactures and markets innovative and original 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 and related companies, employ approximately 31,000 people worldwide. You can visit the company's global website at https://www.otsuka.co.jp/en.

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SOURCE Avanir Pharmaceuticals, Inc.