Alexza Completes Enrollment in Phase 3 Clinical Trial with AZ-004 (Staccato(R) Loxapine) for Acute Agitation
MOUNTAIN VIEW, Calif., June 9 /PRNewswire-FirstCall/ -- AlexzaPharmaceuticals, Inc. (Nasdaq: ALXA) announced today that it has completedenrollment of its first Phase 3 clinical trial with AZ-004 (Staccato(R)loxapine). AZ-004 is an inhalation product candidate being developed for thetreatment of acute agitation in patients with schizophrenia or bipolardisorder. Alexza believes the novel, non-invasive nature and rapidpharmacokinetic (PK) properties resulting from inhaled loxapine administrationvia the Staccato system have the potential to make AZ-004 a viable product totreat acute agitation. AZ-004 is being developed through Symphony Allegro, aproduct development partnership formed between Alexza and Symphony Capital,LLC in 2006.
'We initiated this first Phase 3 clinical trial of our lead program inlate February, completed enrollment in less than four months, and project tohave initial results in late September, which is six months ahead of ouroriginal schedule,' said James V. Cassella, PhD, Alexza Senior Vice President,Research and Development and chairman of the Symphony Allegro DevelopmentBoard. 'We are pleased at the pace this trial enrolled and believe thisindicates clinician enthusiasm for this novel drug candidate.'
'With the early completed enrollment of our first AZ-004 Phase 3 study, weare sharpening our focus and accelerating our AZ-004 pre-commercializationactivities for manufacturing, quality systems, regulatory submissions, andpotential sales and marketing,' said Thomas B. King, Alexza President and CEO.'We also remain on schedule to initiate our second AZ-004 Phase 3 study duringthe third quarter of this year.'
AZ-004 Phase 3 Clinical Trial Design
The first AZ-004 Phase 3 clinical trial enrolled 344 patients withschizophrenia at 24 U.S. clinical centers. The trial is an in-clinic,multi-center, randomized, double-blind, placebo-controlled study, testingAZ-004 at two dose levels, 5 and 10 mg. The trial protocol specified thatpatients were eligible to receive up to 3 doses of study drug in a 24-hourperiod, depending on their clinical status.
The primary endpoint for the study is the reduction in agitation asmeasured by the change from baseline in the PEC Score, measured at 2 hoursafter the first dose. The PEC Score is a commonly used endpoint in acuteagitation studies and is the abbreviation for PANSS (Positive and NegativeSymptom Scale) Excited Component Score. The trial protocol specified thatvarious assessments of a patient's agitation state be conducted at serial timepoints using standard agitation scales over the first 4-hour post-dose timeperiod, with follow-up assessments at the end of the 24-hour study period.Side effects were recorded throughout the 24-hour period.
Alexza projects that the initial results will be reported before the endof September 2008. The second Phase 3 clinical trial is projected to begin inQ3 2008. The design of the second study will be similar to the first trial,except that the patient population will be bipolar disorder patients.
Conference Call Information
The Company will host an investor conference call to discuss today'sannouncement on Monday, June 9, 2008 at 5:15 p.m. Eastern Time. A replay ofthe call will be available for two weeks following the event. The conferencecall, replay and webcast are open to all interested parties.
Domestic callers: 1-800-299-0148 International callers: 1-617-801-9711 Passcode: 11378886 Webcast information: http://www.alexza.com/investor_section/news_events.php
The replay of the conference call may be accessed via the Internet, atwww.alexza.com, or via phone at 1-888-286-8010 for domestic callers or 1-617-801-6888 for international callers. The reference number to enter the replayof the call is 95055607.
About Acute Agitation
Acute agitation, characterized by unpleasant arousal, tension,irritability and hostility, is one of the most common and severe symptoms ofmany major psychiatric disorders, including schizophrenia and bipolardisorder. According to the National Institute of Mental Health (NIMH),schizophrenia afflicts about 6.0 million adults in the United States andbipolar disorder affects about 5.7 million American adults. Company-sponsoredmarket research indicates that over 90% of these patients will experienceagitation during their lifetime and that about 70% of those who experienceagitation will have one to six episodes per year. Agitated patients are oftentreated in an emergency room setting, and are also treated as in-patients inpsychiatric hospitals or psychiatric units in standard hospitals.
Market research indicates that physicians currently treat acute agitationwith intramuscular (IM) injections, rapid-dissolve tablets or standardtablets. IM injections are invasive, can be disconcerting to patients as theyoften require the use of restraints, and can be dangerous to the medicalpersonnel while they attempt to inject the patient. IM injections can alsotake up to 60 minutes to work. Oral tablets provide convenience of dosing buthave a slower onset of action. Market research among physicians hasidentified speed of onset as an important factor that affects their choice oftherapy for treating acute agitation. Published literature suggests that manypatients with schizophrenia or bipolar disorder are able to make informeddecisions regarding their treatment in an acute agitated state and wouldprefer a treatment option that is rapid-acting and noninvasive.
Alexza believes there is a significant unmet medical need for analternative treatment option for acute agitation that will provide a fasteronset of effect, that is non-invasive and safe for medical personnel toadminister, and will facilitate trust between the patient and the treatingclinician.
About AZ-004 (Staccato loxapine)
AZ-004 is the combination of Alexza's proprietary Staccato system withloxapine, a drug belonging to the class of compounds known generally asatypical antipsychotics. The Staccato system technology used in AZ-004 is ahand-held, chemically-heated, single dose inhaler designed to generate anddeliver excipient-free loxapine aerosol for deep lung delivery that results inIV-like pharmacokinetics. Alexza has now completed four clinical trials withAZ-004, this 344 patient Phase 3 study, a 50 subject Phase 1 study, a 129patient Phase 2 study, and a 32 patient multiple-dose tolerability and PKstudy in schizophrenic patients.
The Company believes that the unique delivery of loxapine via the Staccatosystem will provide rapid onset of drug effect, as measured by a reduction inthe signs and symptoms of acute agitation. In March 2007, Alexza announcedpositive initial results from a multi-center, randomized, double-blind,placebo-controlled Phase 2 clinical trial in 129 patients in an in-patientclinical setting. The 10 mg dose of AZ-004 met the primary endpoint of theclinical trial, which was a statistically significant reduction in the measureof agitation from baseline to the 2-hour post-dose time point, as compared toplacebo. The 10 mg dose of AZ-004 also exhibited a rapid onset of effect,with a statistically significant improvement in the PEC scores at 20 minutespost-dose, as compared to placebo, and sustained effectiveness throughout the24-hour study period, as compared to placebo
About Symphony Allegro
In December 2006, Alexza entered into a collaboration with SymphonyCapital LLC, a biotech-focused private equity firm. Under the terms of theagreement, Alexza and Symphony Capital established Symphony Allegro, Inc.,which is providing funding to Alexza to accelerate clinical and other relateddevelopment activities of Staccato loxapine (AZ-004 and AZ-104) and Staccatoalprazolam (AZ-002). Alexza has granted a license to certain intellectualproperty rights for the selected product candidates. Through a purchaseoption, Alexza retains the exclusive right, but not the obligation, to acquire100% of the equity of Symphony Allegro at specified prices during the term ofthe agreement. If Alexza chooses not to exercise the purchase option,Symphony Allegro retains the rights to the product candidates. The purchaseoption expires December 31, 2010.
About Alexza Pharmaceuticals, Inc.
Alexza Pharmaceuticals is an emerging specialty pharmaceutical companyfocused on the development and commercialization of novel, proprietaryproducts for the treatment of acute and intermittent conditions. TheCompany's technology, the Staccato system, vaporizes unformulated drug to forma condensation aerosol that allows rapid systemic drug delivery through deeplung inhalation. The drug is quickly absorbed through the lungs into thebloodstream, providing speed of therapeutic onset that is comparable tointravenous administration, but with greater ease, patient comfort andconvenience.
Alexza has six product candidates in clinical development. Alexza's leadprogram, AZ-004 (Staccato loxapine) for the treatment of acute agitation inschizophrenic or bipolar disorder patients, is in Phase 3 testing. AZ-001(Staccato prochlorperazine) for the acute treatment of migraine headaches hascompleted Phase 2 testing. AZ-104 (Staccato loxapine) for the acute treatmentof migraine headaches and AZ-002 (Staccato alprazolam) for the acute treatmentof panic attacks associated with panic disorder are in Phase 2 testing.Product candidates in Phase 1 testing are AZ-003 (Staccato fentanyl) for thetreatment of breakthrough pain, which is partnered with Endo Pharmaceuticalsin North America, and AZ-007 (Staccato zaleplon) for the treatment ofinsomnia. More information, including this and past press releases fromAlexza is available online at http://www.alexza.com.
Safe Harbor Statement
This press release includes forward-looking statements regarding thepotential timing of the announcement of results of the AZ-004 Phase 3 clinicaltrial, potential benefits of AZ-004, future development of the Company'sproduct candidates and safety of the Company's products and technologies. Anystatement describing the Company's expectations or beliefs is aforward-looking statement, as defined in the Private Securities LitigationReform Act of 1995, and should be considered an at-risk statement. Suchstatements are subject to certain risks and uncertainties, particularly thoseinherent in the process of developing and commercializing drugs. TheCompany's forward-looking statements also involve assumptions that, if theyprove incorrect, would cause its results to differ materially from thoseexpressed or implied by such forward-looking statements. These and otherrisks concerning Alexza's business are described in additional detail in theCompany's Annual Report on Form 10-K for the year ended December 31, 2007, andthe Company's other Periodic and Current Reports filed with the Securities andExchange Commission including the risks under the headings: 'Failure or delayin commencing or completing clinical trials for our product candidates couldharm our business' and 'If our product candidates do not meet safety andefficacy endpoints in clinical trials, they will not receive regulatoryapproval, and we will be unable to market them'. Forward-looking statementscontained in this announcement are made as of this date and the Companyundertakes no obligation to publicly update any forward-looking statement,whether as a result of new information, future events or otherwise