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EX-99.3 - EX-99.3 - Alexza Pharmaceuticals Inc. | d73331exv99w3.htm |
EX-99.2 - EX-99.2 - Alexza Pharmaceuticals Inc. | d73331exv99w2.htm |
8-K - FORM 8-K - Alexza Pharmaceuticals Inc. | d73331e8vk.htm |
Exhibit 99.1
NEWS RELEASE for immediate release
Staccato® Loxapine (AZ-004) Reduced Signs and Symptoms of
Agitation as Early as Ten Minutes After Dosing in Patients
with Schizophrenia or Bipolar Disorder
Agitation as Early as Ten Minutes After Dosing in Patients
with Schizophrenia or Bipolar Disorder
Additional Phase 3 Analyses and Phase 1 Cardiovascular Safety Data
Presented by Alexza Pharmaceuticals at the American Psychiatric
Association 2010 Annual Meeting
Presented by Alexza Pharmaceuticals at the American Psychiatric
Association 2010 Annual Meeting
New Orleans, Louisiana May 26, 2010 Results of clinical studies in patients with schizophrenia
or bipolar disorder demonstrated that Staccato® loxapine (AZ-004) reduced agitation in
patients, regardless of the level of agitation at baseline. Improvement in agitation levels were
observed as early as 10 minutes after dosing on the standard components of agitation as measured by
the Positive and Negative Syndrome Scale Excited Component (PEC). Staccato loxapine also had no
significant hemodynamic effect in subjects taking chronic antipsychotic treatment and did not
significantly prolong the QT interval at therapeutic doses. These and other efficacy and safety
data from clinical trials involving more than 700 patients and subjects were presented in poster
presentations today at the Annual Scientific Sessions of the American Psychiatric Association
meeting in New Orleans, LA.
Staccato loxapine is being developed by Alexza Pharmaceuticals, Inc. (Mountain View, CA) for the
rapid treatment of agitation in patients with schizophrenia or bipolar disorder. Agitation is
distressing for patients and their caregivers as well as a challenge for health-care professionals
to manage. An AZ-004 New Drug Application is currently under review by the U.S. Food and Drug
Administration, with a PDUFA goal date of October 11, 2010. The studies being reported were
sponsored by Alexza, and the AZ-004 rights for the treatment of psychiatric and/or neurological
indications and the symptoms associated with these indications have been licensed in the United
States and Canada to Biovail Laboratories International, SRL, a subsidiary of Biovail Corporation
of Mississauga, Canada.
As previously reported, our Phase 3 studies showed that Staccato loxapine was effective in
relieving the symptoms of agitation, with an onset of effect occurring in as little as 10 minutes.
Additional analyses of our Phase 3 data show that AZ-004 rapidly treated the five individual
dimensions of agitation in patients with schizophrenia or bipolar disorder, said James V.
Cassella, PhD, Senior Vice President, Research and Development, Alexza Pharmaceuticals Inc.
About the AZ-004 Efficacy Studies
The additional efficacy results from two randomized, double-blind, and placebo-controlled Phase 3
clinical trials assessing the efficacy and safety of Staccato loxapine in treating agitation in
patients with
schizophrenia or bipolar disorder were presented in the poster, Treating Agitation
with Inhaled Loxapine (AZ-004): Efficacy Analyses in Patients with Schizophrenia or Bipolar
Disorder (Poster Session 6).
In the Phase 3 clinical trials, loxapine was administered via
inhalation using the Staccato system,
which delivers thermally-generated drug aerosol to the deep lungs for rapid systemic absorption
with IV-like pharmacokinetics. Adults 18 to 65 years of age who met DSM-IV criteria for schizophrenia or
bipolar I disorder, and presented with a relevant degree of agitation at baseline, were included in
the trials. A total of 344 patients with schizophrenia and 314 patients with bipolar I disorder
were randomized to receive either 0 mg, 5 mg or 10 mg of AZ-004 in an in-patient
treatment facility. Up to three doses of AZ-004 could be administered to each patient during the
24-hour study period.
The primary efficacy assessment in the studies was the change from baseline at 2 hours post-dose
using the total PEC score. In each study, change from baseline for each of the five items
comprising the total PEC score (hostility, uncooperativeness, excitement, poor impulse control and
tension, each scored 1-7) was determined starting at 10 minutes post-dose. In addition, patients
were grouped by baseline severity of agitation (median split) using the total PEC scores for each
study and response rates for the higher and lower agitation populations were compared.
Each of the five items comprising the PEC scale improved with AZ-004 treatment, with differences
from placebo starting at 10 minutes after dosing. On average, each item improved 1 to 2 units from
baseline over the first two hours post-dose for both patient groups. Thus, the change in total PEC
score observed with Staccato loxapine treatment derives from similar changes on each of the five
items assessed. The median PEC score at baseline was 17 across the two studies. For the 10 mg
dose groups and patients having a total PEC score of 17 or less at baseline, there was on average a
total PEC score improvement of 8.3 and 8.5 units for patients with schizophrenia and bipolar
disorder, respectively. For patients having a total PEC score of higher than 17 at baseline, there
was on average a total PEC score improvement of 8.9 and 9.7 units for patients with schizophrenia
and bipolar disorder, respectively.
About the AZ-004 Cardiovascular Safety Studies
The cardiovascular safety of Staccato loxapine was assessed in a Phase 1 study of 32 subjects
taking chronic antipsychotic medication and in a thorough QT study (TQT) in 48 healthy volunteers.
These results were presented in the poster presentation, The Cardiovascular Safety of Inhaled
Loxapine (AZ-004) (Poster Session 6).
The Phase 1 study was a double-blind, placebo-controlled, parallel group investigation of the
safety of repeat doses of AZ-004 (at time 0, 4 and 8 hours) in patients 18 to 65 years of age who
were taking chronic antipsychotic medication. Participants were randomly assigned to receive
either 5 mg x 3 doses, 10 mg x 3 doses, 10 mg followed by two doses of 5 mg, or placebo x 3 doses.
There were no clinically significant mean changes in heart rate or blood pressure (BP) with repeat
dosing in subjects on chronic antipsychotic medication. In the highest dose group (10 mg x 3
doses), mean changes from baseline in systolic BP were -1.75, -3.13, and -4.38 mm Hg at 10 minutes
after the first, second and third doses, respectively.
The TQT study was a double-blind, double-dummy, active- and placebo-controlled, 3 period crossover
study investigating the effect on the QT interval of single doses of 10 mg AZ-004, 400 mg oral
moxifloxacin (active control) and placebo. In the TQT study, AZ-004 did not increase QT intervals,
as demonstrated by the upper bound of the one-sided 95% confidence intervals placed on
the point estimate of the placebo-subtracted change of QTcI being less than 10 ms at all eleven
post-dose time points. Moxifloxacin significantly prolonged QTcI by the same metrics,
demonstrating assay sensitivity. There were no clinically significant mean changes in heart rate
or BP following dosing with AZ-004.
About AZ-004
AZ-004 is an anti-agitation therapeutic that combines the proprietary Staccato system with
loxapine, a drug belonging to the class of compounds known generally as antipsychotics. Loxapine
is currently available in oral formulations in the U.S. for the management of the manifestations
of schizophrenia. The Staccato system is a hand-held, chemically-heated, single-dose inhaler that
delivers a drug aerosol to the deep lung that results in IV-like pharmacokinetics and rapid
systemic effects.
About Alexza
Alexza Pharmaceuticals, Inc. (NASDAQ: ALXA) is a pharmaceutical company focused on the research,
development and commercialization of novel, proprietary products for the acute treatment of central
nervous system conditions. Alexzas technology, the Staccato system, provides speed of therapeutic
onset that is comparable to intravenous administration, but with greater ease, patient comfort and
convenience. For more information about Alexza, visit the companys web site at www.alexza.com.
About Biovail Corporation
Biovail Corporation (NYSE: BVF) is a specialty pharmaceutical company engaged in the formulation,
clinical testing, registration, manufacture and commercialization of pharmaceutical products. The
company is focused on the development and commercialization of medicines that address unmet medical
needs in niche specialty central nervous system markets. For more information about Biovail, visit
the companys web site at www.biovail.com.
Caution Regarding Forward-Looking Information and Safe Harbor Statement
To the extent any statements made in this release contain information that is not historical, these
statements are forward-looking statements within the meaning of Section 27A of the Securities Act
of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and may be
forward-looking information under applicable Canadian provincial securities legislation
(collectively, forward-looking statements). These forward-looking statements relate to, among
other things, objectives, goals, targets, strategies, intentions, plans, beliefs, estimates and
outlook, and can generally be identified by the use of words such as believe, anticipate,
expect, intend, plan, will, may, potential and other similar expressions. In addition,
any statements that refer to expectations, projections or other characterizations of future events
or circumstances are forward-looking statements.
Such statements are subject to certain risks and uncertainties, particularly those inherent in the
process of developing and commercializing drugs. Forward-looking statements also involve
assumptions that, if they prove incorrect, would cause results to differ materially from those
expressed or implied by such forward-looking statements. Although Alexza and Biovail believe that
the expectations reflected in such forward-looking statements are reasonable, such statements
involve risks and uncertainties, and undue reliance should not be placed on such statements.
Certain
material factors or assumptions are applied in making forward-looking statements, including, but
not limited to, factors and assumptions regarding the reliability of research findings, and actual
results may differ materially from those expressed or implied in such statements. Important
factors that could cause actual results to differ materially from these expectations include, among
other things: uncertainties associated with the launch of a new product and the accuracy of
associated research, uncertainties with respect to the development path that will be required by
regulatory authorities and uncertainties with respect to the results of future clinical trials, the
regulatory environment and associated filings and approvals.
These and other risks concerning Alexzas business are described in additional detail in Alexzas
Annual Report on Form 10-K for the year ended December 31, 2009, and Alexzas other Periodic and
Current Reports filed with the U.S. Securities and Exchange Commission including the risks under
the headings: We have a history of net losses. We expect to continue to incur substantial and
increasing net losses for the foreseeable future, and we may never achieve or maintain
profitability., We will need substantial additional capital in the future. If additional capital
is not available, we will have to delay, reduce or cease operations. and Regulatory authorities
may not approve our product candidates even if they meet safety and efficacy endpoints in clinical
trials.
These and other risks are detailed from time to time in Biovails filings with the U.S. Securities
and Exchange Commission and the Canadian Securities Administrators, as well as Biovails ability to
anticipate and manage the risks associated with the foregoing. Additional information about these
factors and about the material factors or assumptions underlying such forward looking statements
may be found in the body of this release, as well as under Item 1A. in Biovails most recent Annual
Report on Form 10-K for the fiscal year ended December 31 2009 and under Item 1A. in Biovails most
recent Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2010.
Forward-looking statements contained in this announcement are made as of this date, and neither
Alexza or Biovail undertake any obligation to update any forward-looking statement, whether as a
result of new information, future events or otherwise, except as required by law.
Alexza and Biovail caution that the foregoing list of important factors that may affect future
results is not exhaustive. When relying on forward-looking statements to make decisions with
respect to Alexza or Biovail, investors and others should carefully consider the foregoing factors
and other uncertainties and potential events.
SOURCES: Alexza Pharmaceuticals, Inc., and Biovail Corporation
# # #
Media and investor contact:
Alexza Pharmaceuticals:
|
Thomas B. King | August J. Moretti | ||
President and CEO | Senior Vice President and CFO | |||
650-944-7634 | 650-944-7788 | |||
tking@alexza.com | amoretti@alexza.com | |||
Biovail Corporation:
|
Nelson F. Isabel | |||
Vice-President, Investor Relations and Corporate Communications | ||||
905-286-3000 |
Staccato® is a registered trademark of Alexza Pharmaceuticals, Inc.