FDA Approves Pharmaxis' ARIDOL™ (Mannitol Inhalation Powder) Bronchial Challenge Test Kit for the Assessment of Bronchial Hyperresponsiveness

EXTON, Pa., Oct. 6 /PRNewswire/ -- Pharmaxis, a global specialty pharmaceutical company focused on therapeutic products for chronic respiratory and immune disorders, announced today that it has received approval from the U.S. Food and Drug Administration (FDA) to market ARIDOL™ (mannitol inhalation powder) Bronchial Challenge Test Kit, the first new bronchial challenge test in more than two decades.  ARIDOL is used for the assessment of bronchial hyperresponsiveness in patients six years of age and older who do not have clinically apparent asthma.  ARIDOL should not be used as a standalone tool to assess asthma, but as part of a physician's overall assessment of asthma.  

"Our new bronchial challenge test brings patients and the medical community an effective, accurate, reproducible test that requires minimal preparation and administration time, and can be conducted in a pulmonary function lab or physician's office," said Stephen Beckman, President, Pharmaxis, Inc. "ARIDOL has been proven safe and effective in two Phase III clinical trials, and is widely recognized by experts as a significant addition to the tools available to help in an overall assessment of asthma.  We anticipate commercial availability of ARIDOL in the first quarter of next year."

ARIDOL is a single-use, indirect test that is easy-to-administer, requires minimal preparation time and only a 15% reduction in lung function from baseline.  Many clinicians consider an indirect bronchial challenge test to be preferable to direct challenge tests.(1)

"ARIDOL is an important step in the advancement of bronchial challenge testing because it induces constriction through the release of endogenous inflammatory mediators," said Bill Storms, MD, Clinical Allergist, Colorado Springs, CO.  "We believe that indirect challenges such as ARIDOL correlate better with airway inflammation, a hallmark of asthma."

How ARIDOL Works

The ARIDOL test requires patients to inhale increasing doses of dry powder mannitol from a simple, hand-held device, which causes airways to narrow and contract when airway inflammation is present. The doses are contained in capsules that are administered at one-minute intervals until a positive response is achieved or until all the capsules have been inhaled, indicating a negative result.  A positive response is indicated when there is a 15% reduction in lung function from baseline compared to a 20% fall required by a methacholine challenge test.(2) The lower the dose required to cause bronchoconstriction, the more severe the bronchial hyperresponsiveness.    

"When testing patients for bronchial hyperresponsiveness with a methacholine test, there is the potential for a large reduction in lung function," added Dr. Storms. "In patients with mild symptoms and good lung function, ARIDOL can be useful to support a diagnosis of asthma.  ARIDOL is well tolerated by patients and has demonstrated fewer large drops in lung function than methacholine or exercise."

Other Bronchial Challenge Tests

Unlike other bronchial challenge tests, ARIDOL is a single-use test that requires less preparation time and eliminates reconstitution, use of a nebulizer to administer, clean-up and sterilization.  A positive ARIDOL test is complete in approximately 20 minutes, compared to an average of 44 minutes for a methacholine test.(1)  A methacholine test requires additional equipment to administer and a designated testing room with ventilation.(2)  Tests that use exercise to assess bronchial hyperresponsiveness require special equipment and conditions, and may not be appropriate for patients with physical limitations.

Safety/Efficacy Profile

The safety and efficacy of ARIDOL as a bronchial challenge test were verified in two global Phase III clinical trials, which assessed the effectiveness of the ARIDOL bronchial challenge test in non-asthmatic patients with symptoms suggestive of asthma and clinically diagnosed asthmatic patients six years of age and older.  Approved for use in 19 countries, ARIDOL has been used by more than 44,000 patients, and is marketed in Australia, major European countries and Korea.  

ARIDOL is included in official international guidelines for the clinical assessment of asthma. Organizations and guidelines endorsing ARIDOL include: the International Olympic Committee Medical Commission's Independent Panel, the U.S. Asthma Management Guidelines, the Global Initiative for Asthma (GINA) Report on Global Strategy for Asthma Management and Prevention, the World Anti-Doping Agency and the Australian Asthma Management Handbook.

ARIDOL is the only dry powder bronchial challenge test approved for use in the U.S.

Indication

Mannitol, the active ingredient in ARIDOL, is a sugar alcohol indicated for the assessment of bronchial hyperresponsiveness in patients 6 years of age or older who do not have clinically apparent asthma.  

ARIDOL is not a stand alone test or a screening test for asthma.  Bronchial challenge testing with ARIDOL should be used only as part of a physician's overall assessment of asthma.

Important Safety Information

WARNING: RISK OF SEVERE BRONCHOSPASM

Mannitol, the active ingredient in ARIDOL, acts as a bronchoconstrictor and may cause severe bronchospasm.  Bronchial challenge testing with ARIDOL is for diagnostic purposes only.  Bronchial challenge testing with ARIDOL should only be conducted by trained professionals under the supervision of a physician familiar with all aspects of the bronchial challenge test and the management of acute bronchospasm. Medications (such as short acting inhaled beta-agonist) and equipment to treat severe bronchospasm must be present in the testing area.  If severe bronchospasm occurs it should be treated immediately by administration of a short acting inhaled beta-agonist. Because of the potential for severe bronchoconstriction, bronchial challenge testing with ARIDOL should not be performed in any patient with clinically apparent asthma or very low baseline pulmonary function tests (e.g., FEV(1) <1-1.5 liters or <70% of the predicted values).

ARIDOL is contraindicated in patients with known hypersensitivity to mannitol, the active ingredient in ARIDOL, or to the gelatin used to make the capsules.  The product is also contraindicated for patients with medical conditions that may be compromised by induced bronchospasm or repeated spirometry maneuvers.

Bronchial challenge testing with ARIDOL should not be performed in children less than 6 years of age due to their inability to provide reliable spirometric measurements.

Use with caution in patients with conditions that may increase sensitivity to the bronchoconstricting or other potential effects of ARIDOL such as: severe cough, ventilatory impairment, unstable angina, or active upper or lower respiratory tract infection that may worsen with use of a bronchial irritant.

The most common adverse reactions (rate greater than or equal to 1%) were headache, pharyngolaryngeal pain, throat irritation, nausea, cough, rhinorrhea, dyspnea, chest discomfort, wheezing, retching and dizziness.  No formal drug-drug interaction studies have been conducted with ARIDOL.

About Pharmaxis

Pharmaxis is a global specialty pharmaceutical company involved in the research, development and commercialization of therapeutic products for chronic respiratory and immune disorders.  The company's development pipeline includes Bronchitol™ for cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease (COPD), PXS25 for the treatment of lung fibrosis and PXS4159 for asthma.  Founded in 1998, Pharmaxis is listed on the Australian Securities Exchange (symbol PXS). The company is headquartered in Sydney, Australia with regional offices in the U.S. (Exton, PA), Europe and Asia Pacific.  For more information about Pharmaxis, visit www.pharmaxis.com.

(1) Anderson SD, Charlton B, Weiler JM, et al. Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma. Respir Res. 2009;10:4.

(2) Provocholine® (methacholine chloride powder for inhalation) [prescribing information].  Methapharm Inc. January 2008.

Please call Daina Cardillo at 203-762-8833 for full prescribing information.

SOURCE Pharmaxis