Avanir Pharmaceuticals Announces Zenvia Safety and Efficacy Data from Star Trial Open Label Extension

STUDY HIGHLIGHTS:

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Patients maintained on Zenvia 30/10 mg demonstrated statistically
significant incremental improvement in their CNS-LS scores over the
additional 12-week treatment period of the open-label study (p<0.0001)

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Patients that titrated from Zenvia 20/10 mg to Zenvia 30/10 mg
demonstrated statistically significant incremental improvement in
their CNS-LS scores (p<0.0001)

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Patients originally on placebo that initiated Zenvia 30/10 mg
demonstrated statistically significant improvement in their CNS- LS
scores (p<0.0001)

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Zenvia 30/10 mg was generally safe and well tolerated with 92.9% of
patients completing the 12-week treatment period of the open-label
study

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Reported rates of adverse events (AEs) were low overall, mild to
moderate in nature and consistent with the reported AEs in the
double-blind phase

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The overall mortality rate observed in patients with amyotrophic
lateral sclerosis, or ALS, (a terminal condition) was consistent with
historic norms

"These long term STAR data suggest that the new low dose formulation of
Zenvia provides sustained efficacy by reducing the frequency and
severity of PBA episodes over a 6 month treatment period," said Randall
Kaye, MD, AVANIR's Chief Medical Officer. "This is the first time the
efficacy of Zenvia has been studied beyond 12 weeks and we are very
pleased to see the durability of response over a 24-week period.
Furthermore, the new low dose Zenvia formulation demonstrated a
favorable long term safety and tolerability profile with a low overall
rate of reported adverse events."

"These open-label data from the extension phase of the STAR trial are
the final data elements necessary to submit a complete response to the
FDA approvable letter," said Keith Katkin, AVANIR's President and CEO.
"Our team is working to file a complete response early in the second
calendar quarter of 2010, with an FDA approval decision expected
approximately six months later. If approved by the FDA, we hope to make
Zenvia available as quickly as possible to the significant number of
patients in the U.S. currently suffering from the debilitating episodes
of PBA."

PATIENT DISPOSITION AND EFFICACY RESULTS

Of the 283 patients who completed the 12-week double-blind phase, a
total of 253 patients (or 89.4%) elected to enroll in the open-label
extension; 94 who originally recevied Zenvia 30/10 mg, 76 who originally
received Zenvia 20/10 mg and 83 who originally received placebo. All
patients enrolled in the open-label extension received the Zenvia 30/10
mg dose twice daily in order to collect additional safety data at the
highest tested dose. A total of 235 (or 92.9%) completed the 12-week
treatment period of the open-label study.

In the open-label study, the efficacy endpoint analysis was based on the
change from baseline to end of study using the Center for Neurologic
Studies Lability Scale (CNS-LS). The CNS-LS is a validated instrument
measuring the severity and intensity of PBA. In this efficacy endpoint
analysis, patients originally receiving Zenvia 30/10 mg in the
double-blind phase reported a statistically significant treatment
response over the course of their second 12 weeks of treatment compared
to open-label baseline (p<0.0001). In addition, patients that switched
to Zenvia 30/10 mg from either Zenvia 20/10 mg or placebo achieved a
statistically significant incremental improvement in their CNS-LS scores
compared to baseline which was maintained over the 12-week treatment
period (p<0.0001 for both groups). The efficacy results of the
open-label study are summarized in the table below:

Mean CNS-LS Scores Over Time

                                                                         Original Treatment Cohort
Study Visit                         Total Open-Label Group (30/10 mg)    Zenvia 30/10 mg    Zenvia 20/10 mg    Placebo
                                    N = 253                              N = 94             N = 76             N = 83
Open-Label Baseline                 13.8                                 13.4               13.7               14.4
Visit 2 (day 15)                    11.1                                 10.8               11.9               10.6
Visit 3 (day 42)                    11.1                                 10.7               11.9               10.9
Visit 4 (day 84)                    11.2                                 10.8               11.3               11.5
p-value (day 84 versus baseline)    p <0.0001                            p <0.0001          p <0.0001          p <0.0001

ITT Population -- All patients received Zenvia 30/10 mg in the open label
study; lower scores indicate better response; open-label baseline scores
differ from the end of the double-blind as some patients stopped
receiving therapy between the final double-blind visit and the
open-label baseline visit

SAFETY AND TOLERABILITY RESULTS

Overall, Zenvia was generally safe and well tolerated in this open-label
study. A total of 235 (or 92.9%) of patients completed the 12 weeks of
treatment in the open-label study. The most common reason for early
withdrawals was due to adverse events (AEs). Early withdrawal due to AEs
occurred in 4.0% of patients and the reported AEs were generally mild to
moderate in nature. The most commonly reported AEs are summarized in the
table below:

Most Common Adverse Events

                        Open-Label Phase     Double-Blind Phase*
                        Zenvia 30/10 mg      Zenvia 30/10 mg    Zenvia 20/10 mg    Placebo
                        N = 253              N = 108            N = 102            N = 108
Falls                   40 (15.8%)           22 (20.4%)         14 (13.7%)         22 (20.4%)
Fatigue                 30 (11.9%)           9 (8.3%)           11 (10.8%)         9 (8.3%)
Headache                27 (10.7%)           15 (13.9%)         15 (14.7%)         16 (14.8%)
Urinary Tract Infection 19 (7.5%)            8 (7.4%)           4 (3.9%)           3 (2.8%)
Constipation            17 (6.7%)            7 (6.5%)           7 (6.9%)           9 (8.3%)
Dizziness               17 (6.7%)            20 (18.5%)         11 (10.8%)         6 (5.6%)
Muscular Weakness       17 (6.7%)            6 (5.6%)           5 (4.9%)           4 (3.7%)
Back Pain               16 (6.3%)            5 (4.6%)           5 (4.9%)           4 (3.7%)
Somnolence              16 (6.3%)            11 (10.2%)         9 (8.8%)           10 (9.3%)
Nausea                  15 (5.9%)            14 (13.0%)         8 (7.8%)           10 (9.3%)
Nasopharyngitis         14 (5.5%)            9 (8.3%)           6 (5.9%)           8 (7.4%)
Pain in Extremity       14 (5.5%)            5 (4.6%)           2 (2.0%)           8 (7.4%)

* Data from the double-blind portion of the STAR trial previously
reported; for comparative purposes only, not a head-to-head safety
comparison

The percent of patients reporting at least one serious adverse event
(SAE) was 5.5%. A total of 14 patients experienced SAEs over the course
of the study. None of the SAEs were deemed by the investigators to be
possibly or probably treatment related. No cardiovascular SAEs were
reported.

Overall, there were three deaths in the open-label study, all in
patients with underlying ALS. All three of the deaths were determined by
investigators to be attributable to respiratory failure, which was
consistent with ALS disease progression. No deaths were determined by
the investigator to be possibly treatment related. The ALS mortality
rate of 2.1% in the 12-week open-label study appeared to be consistent
with historic norms of 4% to 6% mortality over 3 months reported in the
epidemiologic literature.(1, 2, 3, 4, 5)

CARDIOVASCULAR SAFETY

During the course of the study, no new cardiovascular safety signals
were observed. There were no clinically meaningful changes in QT
interval, no reported pro-arrhythmic events and no reports of any
cardiovascular SAEs.

Electrophysiological Measures

Analysis of Central Tendency                 Open-Label Phase    Double-Blind Phase Placebo*
                                             Zenvia 30/10 mg     N = 108
                                             N = 253
Mean QTc - Baseline (QTcB/QTcF)              418.1 / 406.7       415.5 / 404.3
Mean QTc - Day 84 (QTcB/QTcF)                419.9 / 410.0       416.8 / 405.8
Mean a^ in Baseline to Day 84 (QTcB/QTcF)    1.5 / 2.1           1.7 / 1.2
Outlier Categorical Analysis (Visit 2 through Visit 4)**
Absolute > 450 msec (QTcB/QTcF)              6.3% / 2.0 %        6.1% / 2.4%
Absolute > 480 msec (QTcB/QTcF)              0.4% / 0.1 %        0.9% / 0.0%
Absolute > 500 msec (QTcB/QTcF)              0.0% / 0.0 %        0.2% / 0.0%
a^ 30 - 60 msec (QTcB/QTcF)                  3.8% / 3.4 %        6.6% / 3.5%
a^ > 60 msec (QTcB/QTcF)                     0.0% / 0.1 %        0.5% / 0.5%
a^ > 90 msec (QTcB/QTcF)                     0.0% / 0.0 %        0.0% / 0.0%

* Data from the placebo group in the double-blind portion of the STAR
trial previously reported; for comparative purposes only, not a
head-to-head comparison

** Percent of EKGs taken over the course of the study per protocol

STAR TRIAL DESIGN

The STAR (Safety, Tolerability and Efficacy Results of AVP-923 in PBA)
trial was a confirmatory Phase III trial of Zenvia in patients with
pseudobulbar affect (PBA). The randomized, multi-center, international
STAR trial compared active treatment with Zenvia 30/10 mg BID and Zenvia
20/10 mg BID to placebo during a 12-week, double-blinded phase, followed
by a 12-week, open-label extension study. At the conclusion of
enrollment of the double-blind phase, AVANIR had enrolled a total of 326
patients (197 with underlying ALS and 129 with underlying MS) who
exhibited signs and symptoms of PBA across 52 sites in the U.S. and
Latin America. A total of 110, 107 and 109 patients were randomized to
the Zenvia 30/10 mg group, the Zenvia 20/10 mg group and the placebo
group, respectively. The primary efficacy analysis was based on the
changes in crying/laughing episode rates recorded in patient diaries.
Secondary endpoints for this clinical trial included: 1) Center for
Neurologic Study-Lability Scale (CNS-LS) score; 2) Neuropsychiatric
Inventory Questionnaire (NPI-Q); 3) SF-36 Health Survey; 4) Beck
Depression Inventory (BDI-II); and 5) Pain Rating Scale score (MS
patients only). Safety and tolerability of Zenvia were determined by
reporting adverse events, physical exam, vital signs, electrocardiogram,
respiratory function tests and clinical assessment of clinical
laboratory variables. A total of 283 patients completed the double-blind
phase and 253 (or 89.4% of eligible patients) enrolled in the 12-week
open label extension. All patients in the open-label extension received
Zenvia 30/10 mg twice daily. Efficacy was assessed at baseline and
during subsequent clinic visits using the CNS-LS score. Safety and
tolerability assessments were the same as in the double-blind phase of
the study. The STAR trial was conducted under a Special
Protocol Assessment (SPA) from the U.S. Food and Drug Administration
(FDA). For more information visit www.pbatrial.com.

ABOUT PBA

Pseudobulbar affect (PBA), also known as emotional lability, is a
neurologic disorder that occurs secondary to neurologic disease or brain
injury causing sudden and unpredictable episodes of crying, laughing, or
other emotional displays. Moderate to severe PBA is estimated to impact
approximately 2 million people in the United States with underlying
neurologic conditions such as multiple sclerosis (MS), amyotrophic
lateral sclerosis (ALS), Parkinson's disease, dementias including
Alzheimer's disease, stroke, and traumatic brain injury. PBA episodes
may occur when disease or injury damages the area of the brain that
controls normal expression of emotion. This damage can disrupt brain
signaling causing a "short circuit" and triggering involuntary PBA
episodes. PBA has been shown to impair the lives of patients in both
social and occupational settings. There are currently no FDA approved
treatments for PBA.

ABOUT ZENVIA

Zenvia(TM) (dextromethorphan/quinidine) is a combination of two
well-characterized compounds: the therapeutically active ingredient
dextromethorphan and the enzyme inhibitor quinidine, which serves to
increase the bioavailability of dextromethorphan. This first-in-class
drug candidate is believed to help regulate excitatory neurotransmission
in two ways: through pre-synaptic inhibition of glutamate release via
sigma-1 receptor agonist activity and through postsynaptic glutamate
response modulation via uncompetitive, low-affinity NMDA antagonist
activity. Zenvia is being developed for the treatment of pseudobulbar
affect (PBA) and has successfully completed a Phase III trial for
diabetic peripheral neuropathic (DPN) pain. In October 2006, the Company
received an approvable letter for Zenvia in the treatment of PBA. The
Company conducted the STAR trial under a Special Protocol Assessment
(SPA) agreement with the FDA with the goal of addressing safety concerns
raised in the Agency's approvable letter for Zenvia in the treatment of
PBA. For more information about this trial visit http://www.pbatrial.com,
and for more information about the Agency's SPA process, see http://www.fda.gov/cder/guidance/3764fnl.htm.
In addition, AVANIR has conducted a Phase III study of Zenvia in DPN
pain where the primary endpoints were successfully met. Subsequently the
Company released top-line results of a formal PK study that identified
alternative lower-dose quinidine formulations of Zenvia for DPN pain
intended to deliver similar efficacy and improved safety/tolerability
versus the formulations previously tested for this indication.

ABOUT AVANIR

AVANIR Pharmaceuticals, Inc. is a biopharmaceutical company focused on
acquiring, developing, and commercializing novel therapeutic products
for the treatment of central nervous system disorders. AVANIR's lead
product candidate, Zenvia, is being developed for the treatment of
pseudobulbar affect (PBA) and has successfully completed a Phase III
trial for diabetic peripheral neuropathic (DPN) pain. AVANIR has
licensed its MIF inhibitor program to Novartis International
Pharmaceuticals Ltd. and has sold its anthrax monoclonal antibody
program to Emergent BioSolutions. The Company's first commercialized
product, Abreva(R) (docosanol), is marketed in North America by
GlaxoSmithKline Consumer Healthcare and is the leading over-the-counter
product for the treatment of cold sores. Further information about
AVANIR can be found at www.avanir.com
and further information about pseudobulbar affect can be found at www.PBAinfo.org.

FORWARD LOOKING STATEMENTS

Statements in this press release that are not historical facts,
including statements that are preceded by, followed by, or that include
such words as "estimate," "intend," "anticipate," "believe," "plan,"
"goal," "expect," "project," or similar statements, are forward-looking
statements that are subject to certain risks and uncertainties that
could cause actual results to differ materially from the future results
expressed or implied by such statements. For example, there can be no
assurance that the U.S. Food and Drug Administration (FDA) will approve
Zenvia for any indication, or that the Company will meet projected
timelines. Risks and uncertainties affecting the Company's financial
condition and operations also include the risks set forth in AVANIR's
most recent Annual Report on Form 10-K and subsequent Quarterly Reports
on Form 10-Q, and from time-to-time in other publicly available
information regarding the Company. Copies of this information are
available from AVANIR upon request. AVANIR disclaims any intent to
update these forward-looking statements.

REFERENCES

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del Aguila, et al, Neurology. 2003 Mar 11;60(5):813-9

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Millul A, et al, Neuroepidemiology. 2005;25(3):114-9

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Riluzole prescribing information, Sanofi-Aventis (survival time from
initiation of therapy)

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Testa D, et al, Amyotroph Lateral Scler Other Motor Neuron Disord.
2004 Dec;5(4):208-12

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Traynor B, et al, J Neuol Neurosurg Psych. 2003;74:1258-1261

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SOURCE: AVANIR Pharmaceuticals, Inc.

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