Message #28 From:
TheMachine Date: April 9, 2009 03:35:25 AM
AVNR Stock News : AVANIR Provides Clinical and Corporate Updates
AVANIR Pharmaceuticals, Inc. (NASDAQ:AVNR) today provided an
update on the STAR trial and announced that it has completed additional
pre-clinical and clinical studies to enhance the complete response to
the approvable letter for the new lower dose Zenvia™ (dextromethorphan
30mg/quinidine 10mg [DM/Q 30/10]) formulation. The Company has also
announced that the NASDAQ exchange has extended the temporary suspension
of bid price requirements, which is expected to permit the continued
listing of the Company’s Common Stock on the NASDAQ Global Market until
at least November 13, 2009.
STAR TRIAL UPDATE
Earlier in March, AVANIR announced it had achieved targeted enrollment
of approximately 300 patients in the STAR trial. At the conclusion of
enrollment, AVANIR had enrolled a total of 326 patients (197 with
underlying ALS and 129 with underlying MS). The incremental patients
will allow AVANIR to further enhance the safety database for the
complete response to the approvable letter and will increase the overall
statistical power of the STAR trial. In addition, the Company continues
to see low overall rates of discontinuations and a high percentage of
eligible patients rolling over into the optional open label extension
study, which compares favorably to previous experience. The Company
reaffirms that it expects top-line data availability no later than
September 2009.
PRECLINICAL CARDIAC STUDIES
In an effort to provide more complete cardiac safety data in the
response to the approvable letter, AVANIR proactively conducted a rabbit
ventricular wedge study (Wedge), a well accepted preclinical model with
a high sensitivity and specificity for identifying medications with a
potential for causing torsades de pointes (TdP), a rare
ventricular arrhythmia.
In the Wedge study, the quinidine concentration comparable to the new
Zenvia 30/10 mg dose had an overall TdP risk score of zero, which was
lower than the original Zenvia 30/30 mg dose.
AVANIR plans on summarizing the Wedge study in addition to two other
pre-clinical studies in its complete response to the FDA approvable
letter for the Zenvia pseudobulbar affect (PBA) application. The
complete response will include a previously completed in vitro
hERG study as well as a canine Purkinje fibers study (Roden et al, Circ.
Res. 1985;56;857-867) on the electrophysiological effects of low
dose quinidine. The findings from all three preclinical studies suggest
that the risk of Zenvia-induced TdP is extremely low at the dosing
levels currently being clinically tested in the ongoing Phase III STAR
trial.
ADVANCED CARDIAC SAFETY STUDY (ACSS)
In support of planned labeling discussions, AVANIR conducted the ACSS to
assess the degree to which the new lower dose Zenvia 30/10 mg
formulation would potentially prolong cardiac QT intervals. Substantial
QT interval prolongation can disrupt the heart's electrical cycle and
result in cardiac arrhythmia. The ACSS was a randomized, double-blind
(except for moxifloxacin), placebo and positive-controlled,
multiple-dose, 3-treatment, crossover study evaluating the ECG effects
of Zenvia 30/10 mg administered in 50 healthy volunteers. Moxifloxacin,
a widely used drug not known to induce TdP was selected as a positive
comparator to establish assay sensitivity. An individual correction
method (QTcI) was utilized to achieve the best possible elimination of
the effect of heart rate on QT duration. The ACSS was designed and
conducted in compliance with the Food and Drug Administration (FDA)
guidance E14 “The Clinical Evaluation of QT/QTC Interval Prolongation
and Proarrhythmic Potential for Non Antiarrhythmic Drugs.”
In the ACSS, the overall effect of the Zenvia 30/10 mg dose on QT
interval was less than the effect of the moxifloxacin 400 mg positive
control. In the study, Zenvia 30/10 mg and moxifloxacin 400 mg produced
maximal mean QTcI changes of 10.3 msec and 12.2 msec and upper bound 95%
one-sided confidence intervals of 14.3 msec and 16.2 msec, respectively.
Additionally, no subject in the study had an absolute QTcI greater than
480 msec and no subject had a change in QTcI greater than 60 msec.
Zenvia 30/10 mg had no significant effect on PR and QRS interval
duration or cardiac morphology. In accordance with FDA guidance
regarding drug candidates that demonstrate an upper bound 95% one-sided
CI above 10 msec, AVANIR will continue to conduct detailed ECG
monitoring throughout the STAR trial and provide this important clinical
cardiac safety information in support of the full response to the FDA
approvable letter.
The frequency and nature of adverse events in the Zenvia group were
comparable to those observed with moxifloxacin and placebo. The most
common adverse events were mild to moderate in severity and there were
no discontinuations due to adverse events. Safety data from the ACSS
suggest that the new Zenvia 30/10 mg dose should exhibit an improved
overall adverse event profile versus the original formulation.
CORPORATE UPDATE
On March 23, 2009 the NASDAQ announced that due to continued
extraordinary market conditions, NASDAQ is further extending the
suspension of the bid price and market value of publicly held shares
requirements. Enforcement of these rules is scheduled to resume on July
20, 2009. As a result, the deadline for AVANIR to regain compliance with
minimum bid price listing requirements for the NASDAQ Global Market is
extended to approximately November 13, 2009.
ABOUT ZENVIA
Zenvia 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
currently in development for the treatment of PBA and diabetic
peripheral neuropathic (DPN) pain. In October 2006, the Company received
an approvable letter for Zenvia in the treatment of PBA. The Company has
initiated a confirmatory Phase III study under a Special Protocol
Assessment (SPA) agreement with the FDA utilizing a new lower quinidine
dose formulation of Zenvia intended to address 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 April 2007, AVANIR announced successfully meeting all primary
endpoints in a Phase III study of Zenvia in DPN pain. In May 2008, 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. AVANIR is
now engaged in discussions with the FDA under the SPA process regarding
the design of the next Phase III study in DPN pain and overall program
requirements.
ABOUT AVANIR
AVANIR Pharmaceuticals, Inc. is focused on acquiring, developing, and
commercializing novel therapeutic products for the treatment of chronic
diseases. AVANIR’s products and product candidates address therapeutic
markets that include the central nervous system, inflammation, and
infectious diseases. AVANIR's lead product candidate, Zenvia, is being
developed for the treatment of PBA and 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®, 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 any new doses of Zenvia for PBA or DPN pain will be safe
and effective, that any additional Phase III trial for Zenvia will be
successful or that the U.S. Food and Drug Administration (FDA) will
approve Zenvia for any indication or that the Company will meet clinical
development 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.
To be included on AVANIR's e-mail alert list; click on the link below or
visit AVANIR's website: http://www.b2i.us/irpass.asp?BzID=958&to=ea&s=0
AVANIR Investor Contacts Eric
Benevich or Brenna Mullen, 949-389-6700 ir@avanir.com
