While the cognitive and negative symptoms of schizophrenia are now a major chronic care issue, the positive symptoms often return as the acute-care focus when patients, due to medication noncompliance and/or the fluctuating intensity of their illness, become agitated, with danger to self or others. Alexza’s Adasuve/loxapine inhalant delivery system has shown efficacy in Phase III testing, for both schizophrenic and bipolar agitation. It offers an alternative to IM or oral antipsychotic administration (oral medications tend to be too slow, and patients often noncompliant) for agitated patients, which may seem a small issue to outside observers, but is not. During this writer’s early psychiatric hospital experience/training, I participated 800-1000 times in the physical immobilization of psychotic, agitated patients, often so that they could be given IM medications. It was and is a primitive process, three or four staff members tackling the patient; hopefully avoiding being punched, kicked, or bitten. Even the IM route lags in its effect for 20-40 minutes, during which time the patient often must remain physically restrained, because recipients of a forcible injection in the buttock tend to not perceive this as compassionate medical care. Forcible IM establishes a climate of coercion and control which is traumatizing, both for the patient being medicated, and for other patients who witness the process. At times, the agitation which required physical restraint spreads amongst other patients, as if contagious. This would be avoided with an inhalant alternative; compliance would undoubtedly be far higher, and its onset of effect much faster. Adasuve produces a very rapid onset of effect (cMax in two minutes), the trials used 10 minutes as the first timepoint, wherein Adasuve produced significant relief of agitation. An inhalant antipsychotic is also an intervention that can be offered earlier in the escalation cycle than IM meds, ‘nipping it in the bud’ before it approaches a dangerous crescendo.
The question is not whether this is a potentially useful tool for dealing with acutely psychotic, agitated patients; it is. The question is whether the American inpatient psychiatry system, which has been gutted by managed care, still exists in large enough scale to provide an adequate market for the product. But the fact is that the highly agitated, psychotic patients who are the key market for Adasuve are still those most likely to be seen in an ER or inpatient setting. From a commercial perspective, the shrinkage of the inpatient psychiatric world means that marketing Adasuve to psych units and emergency rooms would be manageable for a small sales force. There will be some price point sensitivity for Adasuve relative to IM haloperidol, though IM Geodon is also premium-priced. But there are hidden costs to IM med use in terms of staff time, both for the medication administration itself and the incident reports that have to be completed for each involuntary restraint/medication. Our 2009 estimate of market penetration yielded annual sales potential in the $200-225 million range. With the subsequent REMS restrictions in terms of screening patients who might be vulnerable to bronchospasm (Correction: we had not taken into consideration the effect of the REMS on outpatient/home use, which is going to be greatly reduced if not eliminated entirely), and even with EU approval now appearing probable, the peak annual sales estimate is revised to $200 million. For a company of Alexza’s size, this represents a very important ‘win.’