Alexza Pharma Announces U.S. Approval Of ADASUVE sNDA

MOUNTAIN VIEW, Calif. and BARCELONA, Spain, Oct. 10, 2016 /PRNewswire/ -- Alexza Pharmaceuticals, Inc., a wholly-owned subsidiary of Ferrer Therapeutics, Inc., today announced that its supplemental New Drug Application (sNDA) seeking certain changes in the product label and modifications to the Risk Evaluation Mitigation Strategy (REMS) Program for ADASUVE^® (loxapine) inhalation powder (10mg) has been approved by the U.S. Food and Drug Administration (FDA). ADASUVE is the first and only orally inhaled medicine for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.

ADASUVE is administered through Alexza’s innovative proprietary Staccato^® single-use, hand held drug delivery technology system. The Staccato system allow for rapid systemic delivery by inhalation of a thermally-generated aerosol of loxapine, a first generation antipsychotic, to the lung. Administration of ADASUVE results in rapid absorption of loxapine, with a maximum plasma concentration achieved in approximately 2 minutes.

The original FDA approval of ADASUVE was based on the clinical efficacy of inhaled loxapine, demonstrated in two pivotal clinical trials of treating acute agitation: one in patients with schizophrenia and one in patients with bipolar I disorder. Patients receiving ADASUVE experienced a statistically significant reduction in agitation at two hours, the primary endpoint of the studies. These studies demonstrated a 49% reduction in agitation symptoms from baseline in schizophrenia patients, as compared to 33% in patients receiving placebo; and a 53% reduction from baseline in bipolar I patients, as compared to 27% in patients receiving placebo. In these two studies, reduction of agitation was rapidly achieved at 10 minutes post-dose, the first time point studied in the trials, with a 19% reduction in agitation from baseline in schizophrenia patients and a 23% reduction in bipolar I patients, both as compared to 10% in patients receiving placebo.

The approved sNDA includes changes to the prescribing information and modifications to the ADASUVE REMS. The approved product label changes and corresponding REMS modifications include removal of the requirement for immediate access on-site to equipment and personnel trained to manage acute bronchospasm, including advanced airway management (intubation and mechanical ventilation). As modified by the sNDA, the updated ADASUVE label and REMS require that certified Health Care Settings must have immediate access on-site to supplies and personnel trained to manage acute bronchospasm and ready access to emergency response services. Facilities must have a short-acting bronchodilator, including a nebulizer and inhalation solution, for immediate treatment of bronchospasm.

The labeling changes consist of revisions to the Boxed Warning and Warning and Precautions sections of the Prescribing Information.

For additional information please visit Drugs@FDA (www.accessdata.fda.gov).

ADASUVE was first commercially available in the U.S. in March 2014. Alexza reacquired the U.S. commercial rights to ADASUVE in February 2016. The sNDA was filed in December 2015 following discussions with FDA regarding the REMS, including the impact of certain requirements in the previous REMS on product use and accessibility. Updated prescribing information and modifications to the REMS will permit product use and accessibility in additional institutions that would not have qualified under the previous REMS, while still ensuring the safe use of the product.

In the U.S., approximately 2.4 million adults have schizophrenia and approximately 5.7 million adults have bipolar disorder. More than 90% of patients with schizophrenia or bipolar disorder will experience agitation in their lifetimes.ⁱ Patients experiencing agitation associated with schizophrenia or bipolar I disorder often manifest behaviors that interfere with their care, such as threatening behaviors, escalating or urgently distressing behavior or self-exhausting behavior that lead clinicians to use rapidly absorbed antipsychotic medications to help control the agitation quickly.

Please see additional important safety information including the Boxed Warning and the updated REMS Program information below. The most common adverse reactions (greater than at least 2% in the treated group and greater than the occurrence in the placebo group) in short-term, placebo-controlled trials were dysgeusia (abnormal taste), sedation and throat irritation.

ADASUVE is currently available through McKesson and HD Smith as distributors. Please call (888) 832-6378 or visit www.ADASUVE.com for additional information.

ADASUVE^® Prescribing Information (U.S.)
Please click here for Full Prescribing Information, including Boxed WARNINGS.

For more information about ADASUVE, visit www.ADASUVE.com.

For REMS Program information, visit www.ADASUVEREMS.com or call (855)-755-0492.

INDICATIONS AND USAGE
ADASUVE (loxapine) inhalation powder, for oral inhalation use, is a typical antipsychotic indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Efficacy was demonstrated in 2 trials in acute agitation: one in schizophrenia and one in bipolar I disorder.

Limitations of Use: ADASUVE must be administered only in an enrolled healthcare facility.

IMPORTANT SAFETY INFORMATION (see full prescribing information for complete boxed warning)

• ADASUVE is contraindicated in patients with the following:
  • Current diagnosis or history of asthma, COPD, or other lung disease associated with bronchospasm
  • Acute respiratory signs/symptoms (eg, wheezing)
  • Current use of medications to treat airways disease, such as asthma or COPD
  • History of bronchospasm following ADASUVE treatment
  • Known hypersensitivity to loxapine or amoxapine
• ADASUVE must be administered only by a healthcare professional
• Prior to administration, all patients must be screened for a history of pulmonary disease and examined (including chest auscultation) for respiratory abnormalities (eg, wheezing)
• Administer only a single 10 mg dose of ADASUVE within a 24-hour period by oral inhalation using the single-use inhaler
• After ADASUVE administration, patients must be monitored for signs and symptoms of bronchospasm at least every 15 minutes for at least 1 hour
• ADASUVE can cause sedation, which can mask the symptoms of bronchospasm
• Antipsychotic drugs can cause a potentially fatal symptom complex called Neuroleptic Malignant Syndrome (NMS), manifested by hyperpyrexia, muscle rigidity, altered mental state, irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia. Associated features can include escalated serum creatine phosphokinase (CPK) concentration, rhabdomyolysis, elevated serum and urine myoglobin concentration, and renal failure. If NMS occurs, immediately discontinue antipsychotic drugs and other drugs that may contribute to the underlying disorder, monitor and treat symptoms, and treat any concomitant serious medical problems
• ADASUVE can cause hypotension, orthostatic hypotension, and syncope. Use with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions that would predispose patients to hypotension. In the presence of severe hypotension requiring vasopressor therapy, epinephrine should not be used
• Use ADASUVE with caution in patients with a history of seizures or with conditions that lower the seizure threshold. ADASUVE lowers the seizure threshold. Seizures have occurred in patients treated with oral loxapine and can also occur in epileptic patients
• Use caution when driving or operating machinery. ADASUVE can impair judgment, thinking, and motor skills
• The potential for cognitive and motor impairment is increased when ADASUVE is administered concurrently with other CNS depressants
• Treatment with antipsychotic drugs caused an increased incidence of stroke and transient ischemic attack in elderly patients with dementia-related psychosis; ADASUVE is not approved for the treatment of patients with dementia-related psychosis
• Use of ADASUVE may exacerbate glaucoma or cause urinary retention
• The most common adverse reactions (incidence 2% and greater than placebo) in clinical studies in patients with agitation treated with ADASUVE were dysgeusia, sedation, and throat irritation
• Pregnancy Category C. Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk of extrapyramidal and/or withdrawal symptoms after delivery. ADASUVE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
• Nursing mothers: Discontinue drug or nursing, taking into account the importance of the drug to the mother
• The safety and effectiveness of ADASUVE in pediatric patients have not been established

About Alexza Pharmaceuticals, Inc.
Alexza Pharmaceuticals is focused on the research, development, and commercialization of novel, proprietary products for the acute treatment of central nervous system conditions.

Alexza’s products and development pipeline are based on the Staccato system, a hand-held inhaler designed to deliver a pure drug aerosol to the deep lung, providing rapid systemic delivery and therapeutic onset, in a simple, non-invasive manner. Active pipeline product candidates include AZ-002 (Staccato alprazolam) for the management of epilepsy in patients with acute repetitive seizures.

ADASUVE^® is Alexza’s first commercial product. ADASUVE is approved for marketing in 42 countries and has been submitted for approval in seven additional countries. ADASUVE has been launched and is currently available in 22 countries. Ferrer is responsible for commercialization of ADASUVE in Europe, Latin America, the Commonwealth of Independent States countries, the Middle East and North Africa countries, Korea, the Philippines and Thailand. Alexza is actively seeking commercial partners for ADASUVE in other territories of the world.

ADASUVE^® and Staccato^® are registered trademarks of Alexza Pharmaceuticals, Inc. For more information about Alexza, the Staccato system technology or Alexza’s development programs, please visit www.alexza.com.

About Ferrer
Founded in 1959, Ferrer is a privately-held European R&D-based pharmaceutical company headquartered in Barcelona. It is active in the pharmaceutical, health, fine chemicals and food sectors in Europe, Latin America, Africa, the Middle East, Asia and the United States. In total, Ferrer’s human healthcare products are commercialized in more than 95 countries, through 24 international affiliates (including joint ventures) and 70 partners and distributors.

Ferrer carries out activities throughout the full pharmaceutical value chain, from R&D to international marketing, including fine chemical development and the manufacturing of both raw materials and finished pharmaceuticals. Its research centers in Spain and Germany, and manufacturing sites in Europe and Latin America cover the pharmaceutical, diagnostics, vaccine, fine chemical, food and feed sectors. For more information, visit www.ferrer.com.

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SOURCE Alexza Pharmaceuticals, Inc.