Agitation on the rise

NEW for the RAPID TREATMENT OF AGITATION in your patients with schizophrenia or bipolar disorder

WHEN AGITATION IS ON THE RISE…

Agitation/Treatment

NEW for the RAPID TREATMENT OF AGITATION in your patients with schizophrenia or bipolar disorder

INTERCEPT BEFORE THE EPISODE ESCALATES Your agitated patient…A candidate for ADASUVE

Presenting symptoms • Pacing • Pressured speech

8

According to the American Association for Emergency Psychiatry (AAEP)

|

James G.*

3 CENTRAL GOALS FOR TREATING AGITATION

Age 38

Rapid tranquilization without oversedation

Ease of administration of medication

Creating a therapeutic alliance during treatment

• Clenching fists • Defensive demeanor

History of psychiatric illness • Bipolar 1 disorder

AGITATION IS A COMMON THREAT IN BIPOLAR DISORDER AND SCHIZOPHRENIA

ADASUVE IS A PORTABLE INHALER UNIQUELY SUITED FOR THE TREATMENT OF AGITATION

• DSM-IV-TR defines psychomotor agitation as: “Excessive motor activity associated with a feeling of inner tension. The activity is usually nonproductive and repetitious and consists of such behavior as pacing, fidgeting, wringing of the hands, pulling of clothes, and inability to sit still”3

Indicated for the rapid treatment of agitation associated with schizophrenia or bipolar disorder in adults

1,2

• Agitation can escalate from mild signs to moderate to aggressive behavior, potentially reaching the point of verbal and physical assault1,4,5 Breath actuated

Needle free

Fast, reliable delivery9

Based on US reported estimates of potential rates…1,6,7 1.5 million annual

psychiatric emergency visits may involve agitation

• 13% may involve agitated patients with bipolar disorder • 21% may involve agitated patients with schizophrenia

ADASUVE offers an effective, noninvasive approach that is appropriate across health care settings9

As agitation rises, so too does the risk for patient suffering, caregiver burden, and disruption to the safety and flow of the health care environment 1,2,4,5

*Not an actual patient.

2

Please see accompanying full Prescribing Information for ADASUVE.

INTERCEPT WITH ADASUVE

3

NEW for the RAPID TREATMENT OF AGITATION in your patients with schizophrenia or bipolar disorder

ADASUVE SIGNIFICANTLY REDUCED AGITATION SEVERITY VS PLACEBO STARTING AT 10 MINUTES

9,10

MAXIMUM PLASMA CONCENTRATION WAS ACHIEVED WITHIN 2 MINUTES AFTER USE 9

Proven in 2 double-blind, randomized, placebo-controlled Phase 3 efficacy trials 140

Mean change from baseline in PEC score through 2 hours after a single dose of ADASUVE Plasma Concentration (ng/mL)

120

Agitated Patients With Bipolar Disorder PEC Score, Change From Baseline

Time After Treatment

0

10 min

30 min

60 min

90 min

120 min

–2 –4

*

100 80 60 40

0

–8

0.5

1

2

*

% Reduction

ADASUVE 5 mg (N=104) ADASUVE 10 mg (N=105)

at 10 min

5

10

30

45

60

53

Placebo (N=105)

Reduction

3

Time After Treatment (minutes)

10 mg

10 mg

23%

Mean±SEM

ADASUVE 5 mg (N=7) ADASUVE 10 mg (N=8)

20

–6

–10

Efficacy

Mean plasma concentrations of loxapine following administration of ADASUVE10

at 2 hrs

*P<0.0001 vs placebo.

ADASUVE DELIVERED LASTING IMPROVEMENT

Agitated Patients With Schizophrenia PEC Score, Change From Baseline

Time After Treatment

0

10 min

30 min

60 min

90 min

120 min

Rapid and sustained reduction of agitation severity vs placebo throughout the 24-hour study 9,10

–2 –4

*

In 2 double-blind, randomized, placebo-controlled Phase 3 efficacy trials:

–6 –8 –10

*

19

Mean±SEM

% Reduction at 10 min

76% of patients

10 mg

10 mg Placebo (N=115) ADASUVE 5 mg (N=116) ADASUVE 10 mg (N=112)

49

% Reduction at 2 hrs

*P<0.0001 vs placebo.

with bipolar disorder

did not require another dose

75% of patients

of ADASUVE or additional medication at 4 hours

with schizophrenia

4

4

taking the 10-mg dose

PEC=PANSS Excited Component. Intent-to-treat population with last observation carried forward. Agitation symptoms measured: tension, excitement, poor impulse control, uncooperativeness, hostility. Mean baseline PEC score was 17 to 18.

(vs 36% and 56%, respectively, of those taking placebo)10

Please see accompanying full Prescribing Information for ADASUVE.

INTERCEPT WITH ADASUVE

5

NEW for the RAPID TREATMENT OF AGITATION in your patients with schizophrenia or bipolar disorder

2 Hours After Administration…

SIGNIFICANTLY GREATER IMPROVEMENT WAS REPORTED WITH ADASUVE VS PLACEBO

ADASUVE CALMED PATIENTS MORE EFFECTIVELY THAN PLACEBO…

More than 2 out of 3 patients were “much” or “very much improved” according to investigators’ clinical global impression (CGI)

But did not induce a deep or unarousable sleep

10

Mean ACES scores show that patients receiving ADASUVE were calmer at 2 hours than those receiving placebo10

Percentage of patients who were CGI responders at 2 hours defined as either very much improved (1) or much improved (2)

66%

36%

28%

67%

57%

P<0.0001

P<0.0001

50%

25%

74%

P<0.0001

AGITATION

75%

P=0.0015

8 7 6

4 3 2 1

5.1

4.7

5

3.3 2.1

2.0 Baseline

2 hours

Placebo (N=105)

Baseline

Efficacy

CGI-I Score at 2 Hours

100%

Patients With Bipolar Disorder 9 SLEEP

Agitated Patients With Schizophrenia

CALMNESS

Agitated Patients With Bipolar Disorder

2.1 2 hours

5 mg ADASUVE (N=104)

Baseline

2 hours

10 mg ADASUVE (N=105)

0% Placebo (N=105)

5 mg ADASUVE 10 mg ADASUVE (N=104) (N=105)

Placebo (N=115)

5 mg ADASUVE 10 mg ADASUVE (N=116) (N=112)

Patients With Schizophrenia

1

VERY MUCH IMPROVED

4

NO CHANGE

6

MUCH WORSE

2

MUCH IMPROVED

5

MINIMALLY WORSE

7

VERY MUCH WORSE

3

MINIMALLY IMPROVED

AGITATION

Improvement was assessed by the treating investigator at 2 hours vs baseline on a 7-point scale

CALMNESS

SLEEP

9 8 7 6 5 4 3 2 1

2.3 Baseline

2.2

2.2 2 hours

Placebo (N=115)

4.9

4.7

3.9

Baseline

2 hours

5 mg ADASUVE (N=116)

Baseline

2 hours

10 mg ADASUVE (N=112)

ACES=Agitation Calmness Evaluation Scale. Rates patients on a 9-point continuum ranging from markedly agitated (1) to unarousably asleep (9).

6

Please see accompanying full Prescribing Information for ADASUVE.

INTERCEPT WITH ADASUVE

7

NEW for the RAPID TREATMENT OF AGITATION in your patients with schizophrenia or bipolar disorder

INNOVATIVE STACCATO TECHNOLOGY SUPPORTS SPEED OF ONSET AND EASE OF USE ®

Handheld, single-use inhaler provides single-breath activation and drug delivery to rapidly treat agitation10 • Vaporizes pure loxapine to form an aerosol that is quickly absorbed through the lungs and into the bloodstream10

INSTRUCTIONS FOR USING ADASUVE

9

For oral inhalation only Read the following 5 steps before administering ADASUVE to a patient:

1

• Requires no excipients10

Do not open the pouch until ready to use.

Tear open the foil pouch and remove the product from the package.

• All patients in Phase 3 trials were able to use the device properly10

The recommended dose of ADASUVE

10 mg administered by oral inhalation9

• A lower dose of 5 mg may be considered when clinical factors warrant

2

Use within 15 minutes after removing the tab to prevent automatic deactivation of the product.

Instruct the patient to:

• Following the initial dose, cumulative doses up to a total of 30 mg/day may be given if agitation persists 3

Hold the product away from the mouth and breathe out fully to empty lungs.

4

Inhale through the mouthpiece with a steady deep breath.

5

Remove the mouthpiece from the mouth and hold breath briefly.

Dosing/Administration

Needle-free, collaborative delivery may help support your therapeutic alliance with patients

Firmly pull the plastic tab from the rear of the product. A green light on the top of the product turns on indicating that the product is ready for use.

Note that the green light automatically turns off after the medication has been delivered.

If the light does not turn off, instruct the patient to repeat the inhalation steps.

8

Please see accompanying full Prescribing Information for ADASUVE.

INTERCEPT WITH ADASUVE

9

NEW for the RAPID TREATMENT OF AGITATION in your patients with schizophrenia or bipolar disorder

SAFETY AND TOLERABILITY

IMPORTANT SAFETY INFORMATION

Adverse events (AEs) were limited and unlikely to interfere with successful short-term treatment9 Adverse events in 3 short-term, placebo-controlled trials in patients treated with ADASUVE ADASUVE System Organ Class Preferred Term

Percentage of Patients Reporting an AE* Placebo (N=263)

5 mg ADASUVE (N=265)

10 mg ADASUVE (N=259)

All ADASUVE (N=524)

11%

14%

13%

2%

1%

2%

10%

12%

12%

12%

0%

1%

3%

2%

Gastrointestinal Disorders Dysgeusia

5%

General Disorders and Administration Site Conditions Fatigue

2%

Nervous System Disorders Sedation/somnolence† Respiratory Disorders Throat irritation

*AEs reported by at least 2% of patients treated with either ADASUVE 5 mg or 10 mg, except AEs that had an incidence equal to or less than placebo. †

Rates for sedation and somnolence AEs are combined.

In 24-hour, placebo-controlled clinical trials…9 • There was a low occurrence of extrapyramidal symptoms: 4 patients (<1%) of >500 patients with agitation who received ADASUVE

Please see accompanying full Prescribing Information for ADASUVE.

INTERCEPT WITH ADASUVE

• There was a low incidence of hypotension: ADASUVE 5 mg, 0.8%; ADASUVE 10 mg, 0.4%; and placebo, 0.8%

10

Important Safety Information

• Respiratory events were infrequently reported

References: 1. Sachs GS. A review of agitation in mental illness: burden of illness and underlying pathology. J Clin Psychiatry.

2006;67(suppl 10):5-12. 2. Citrome L. Atypical antipsychotics for acute agitation: new intramuscular options offer advantages.

Postgrad Med. 2002;112(6):85. 3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (revised 4th ed). Washington, DC: American Psychiatric Association; 2000:819. 4. Owen C, Tarantello C, Jones M, Tennant C. Violence and aggression in psychiatric units. Psychiatr Serv. 1998;49(11):1452-1457. 5. Battaglia J. Pharmacological management of acute agitation. Drugs. 2005;65(9):1207-1222. 6. Marco CA, Vaughan J. Emergency management of agitation in schizophrenia.

Am J Emerg Med. 2005;23:767-776. 7. Allen MH, Currier GW. Use of restraints and pharmacotherapy in academic psychiatric emergency services. Gen Hosp Psychiatry. 2004;26:42-49. 8. Allen MH, Currier GW, Carpenter D, Ross R, Docherty JP. The expert consensus guideline series: treatment of behavioral emergencies. J Psychiatr Pract. 2005;11(suppl 1):1-25. 9. Adasuve Prescribing Information. Mountain View, CA: Alexza Pharmaceuticals; 2010. 10. Data on file. Alexza Pharmaceuticals.

• No clinically relevant abnormalities in ECG findings were reported, and a thorough QT study was negative

11

When agitation is on the rise...

INTERCEPT WITH ADASUVE NEW for the RAPID TREATMENT OF AGITATION in your patients with schizophrenia or bipolar disorder • Significantly reduced agitation severity vs placebo starting at 10 minutes—and sustained reductions throughout the 24-hour study 9,10 • Calmed patients significantly more effectively than placebo, without excess sedation10 • Handheld, single-use inhaler provides single-breath activation and drug delivery to rapidly treat agitation10

Inpatient or outpatient, across the agitation continuum— when an episode presents, ADASUVE delivers

Breath actuated

Needle free

Please see accompanying full Prescribing Information for ADASUVE. ADASUVE is a trademark of Biovail Laboratories International SRL (subsidiary of Biovail Corporation) and STACCATO is a registered trademark of Alexza Pharmaceuticals, Inc. © 2010 Biovail Corporation. All rights reserved.

Printed in USA. XXXXXXXX November 2010

Fast, reliable delivery9