The US Food and Drug Administration (FDA) has approved Alexza Pharmaceuticals' Adasuve (loxapine) inhalation powder 10 mg for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Adasuve combines Alexza's proprietary Staccato delivery system with the antipsychotic drug, loxapine.

The Staccato system is a hand-held inhaler that delivers a drug aerosol to the deep lung that results in rapid systemic delivery and absorption of a drug.

"The approval of Adasuve is an important event in the treatment of agitation.  Adasuve is the first approved non-injectable therapy for the acute treatment of agitation in adults with schizophrenia and bipolar I disorder. As noted in the consensus guidelines for Best Practices in the Evaluation and Treatment of Agitation, we believe that the ability to deliver medications rapidly and non-invasively will be important for patients and the professionals who care for them," said Thomas B King, president and CEO of Alexza. "This is a landmark day for Alexza and we are proud of our accomplishments in developing this unique product.  We project that Adasuve will be available for commercial launch early in the third quarter of 2013."

"The data we have seen from the Adasuve phase III clinical trials in patients with schizophrenia and bipolar I disorder are compelling," said Michael Lesem , MD, executive medical director, Claghorn-Lesem Research Clinic, Houston, Texas and a principal investigator in the Adasuve clinical trials. "I believe that Adasuve represents an important new and much needed therapeutic option in treating agitation patients who will benefit from a non-coercive therapeutic intervention that works quickly to relieve their symptoms."

The FDA approval is based on a clinical data package involving more than 1,600 patients and subjects. In two phase III trials, Adasuve was found to be effective in the acute treatment of agitation in adults with schizophrenia or bipolar I disorder.  In these two studies, Adasuve 10 mg met the primary efficacy endpoint, with statistically significant reductions in agitation as compared to placebo at the two-hour post-dose time point, as well as the principal secondary endpoint. Of note, Adasuve exhibited rapid effects in agitated patients, with statistically significant reductions in agitation apparent starting at 10 minutes following administration of a dose versus placebo.

As part of the Adasuve development programme, Alexza identified a risk of bronchospasm in certain asthma and chronic obstructive pulmonary disease (COPD) patients following dosing with Adasuve. It is important to note that Adasuve can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest. Adasuve will be available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Adasuve REMS.

Adasuve is a typical antipsychotic indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Efficacy was demonstrated in two trials in acute agitation: one in schizophrenia and one in bipolar I disorder.

Adasuve must be administered only in an enrolled healthcare facility.

Adasuve can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest. Adasuve is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Adasuve REMS.

Administer Adasuve only in an enrolled healthcare facility that has immediate access on-site to equipment and personnel trained to manage acute bronchospasm, including advanced airway management (intubation and mechanical ventilation).

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.  Adasuve is not approved for the treatment of patients with dementia-related psychosis.

Adasuve is contraindicated in patients with the following: current diagnosis or history of asthma, chronic obstructive pulmonary disease (COPD), or other lung disease associated with bronchospasm, acute respiratory signs / symptoms (e.g., wheezing), current use of medications to treat airways disease, such as asthma or COPD, history of bronchospasm following Adasuve treatment, known hypersensitivity to loxapine and amoxapine.

The most common adverse reactions (incidence = 2% and greater than placebo) in clinical studies in patients with agitation treated with Adasuve were dysgeusia, sedation, throat irritation.

Adasuve will be available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Adasuve REMS.  Adasuve should only be administered in a healthcare facility enrolled in the Adasuve REMS program that has immediate access on-site to equipment and personnel trained to manage acute bronchospasm, including advanced airway management (intubation and mechanical ventilation).  In addition to product labeling, Alexza developed the Adasuve REMS with the purpose of mitigating the risk of bronchospasm.  The Adasuve REMS includes a communication plan and an "elements to assure safe use" of the product, including provisions designed to ensure that Adasuve will only be dispensed in healthcare settings that are enrolled in the Adasuve REMS programme.

With the Adasuve NDA approval, Alexza also has several post-approval requirements, including a large observational clinical trial designed to gather patient safety data based on the real-world use of Adasuve, as well as a clinical program addressing the safety and efficacy of Adasuve in agitated adolescent patients.

Agitation is a serious medical problem that can present in a number of psychiatric disorders, including schizophrenia and bipolar I disorder.

Agitation episodes may escalate unpredictably and, in some cases, necessitate chemical or physical restraint to relieve the individual's distress and to protect care providers and others in close proximity.  Rapid, effective and safe intervention is key to returning the agitated person to a less agitated state.

Alexza is a pharmaceutical company focused on the research, development and commercialization of novel, proprietary products for the acute treatment of central nervous system conditions.