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ALLIANCE FOR HUMAN RESEARCH PROTECTION

Promoting Openness, Full Disclosure, and Accountability

http://www.ahrp.org

FYI

An expanded critique of FDA's astonishing approval of asenapine--a drug

whose efficacy is disputed by FDA's statistician, and whose serious safety

issues emerged in early trials conducted in young, healthy volunteers,

resulting in the termination of several studies due to severe cardiac

events, is posted at: http://www.ahrp.org/cms/content/view/628/1/

It is astonishing that FDA would approve Asenapine for the treatment of

schizophrenia and bipolar disorder disorder--

inasmuch as its efficacy remains in doubt, and 94% of the drug's serious

adverse events were exacerbations of psychiatric illness.

FDA's failure to consider the compelling evidence of hazards posed by the

so-called 'atypical' antipsychotics--from two major government-sponsored,

long-term NIMH studies when assessing the safety / efficacy of asenapine--is

irresponsible.

1. The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)

in schizophrenia study overturned industry-promoted assumptions about the

safety and efficacy of antipsychotics of asenapine's class. The CATIE study

demonstrated the lack of improved efficacy of  'atypical' antipsychotic

drugs from older neuroleptics, while documenting these drugs' severe,

debilitating, life-shortening adverse effects and poor patient outcomes.

The data from the sponsor's asenapine trials raise even greater concerns

about this drug's safety--as analyzed by FDA's primary biopharmaceutics

(OCP) reviewer.

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/D

rugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM173877.pdf

2. The  STEP-BD (Systematic Treatment Enhancement Program for Bipolar

Disorder) found that the use of second generation antipsychotic (Risperdal)

was LEAST effective (4.6%) compared to an anti-convulsant (Lamitcal, 23.8%)

or even a sugar pill (Inositol, 17.4%).

Furthermore, evidence from STEP-D shows that "Suicidal ideation was

significantly more prevalent among patients who were taking a

second-generation antipsychotic than those who were not (26 percent and 17

percent) and those who were taking an antidepressant and those who were not

(25 percent and 14 percent)."

See, Suicidal Ideation and Pharmacotherapy Among STEP-BD Patients,

Psychiatric Services, 2007.

Contact: Vera Hassner Sharav

veracare@ahrp.org

212-595-8974

http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id

=3150

American Society of Health System Pharmacists

Asenapine Approved for Treatment of Schizophrenia, Bipolar Disorder

Kate Traynor

BETHESDA, MD 14 August 2009-FDA and Schering-Plough Corporation today

announced the approval of asenapine sublingual tablets for the acute

treatment of schizophrenia and manic or mixed episodes associated with

bipolar I disorder in adults.

Schering-Plough expects the atypical antipsychotic drug to be available

during the final quarter of this year under the brand name Saphris.

As with other drugs in the class, the labeling (PDF) for asenapine includes

a boxed warning stating that the drug is "not approved" for use in elderly

patients with dementia-related psychosis. Patients with this condition who

are treated with antipsychotic drugs are at increased risk of death, the

labeling warns.

The labeling also warns that cerebrovascular accidents and transient

ischemic attacks have occurred in elderly patients with dementia-related

psychosis when treated with antipsychotic drugs.

Efficacy data on asenapine were collected during three six-week clinical

trials in patients with schizophrenia and two three-week trials in patients

with bipolar disorder. According to FDA, the drug outperformed placebo in

both bipolar-disorder trials and two of the schizophrenia studies.

The most frequent adverse events reported by clinical trial participants

with schizophrenia were restlessness, decreased oral sensitivity, and

drowsiness. Among patients with bipolar disorder, the most frequent adverse

events were drowsiness, dizziness, movement disorders, and weight gain.

Instances of tardive dyskinesia, a serious movement disorder, were reported

during clinical trials of asenapine. The labeling states that if this

condition occurs, consideration should be given to discontinuing therapy

when "clinically appropriate."

Cessation of therapy is also recommended if neuroleptic malignant syndrome

(NMS), a life-threatening neurologic condition associated with the use of

antipsychotic drugs, occurs during treatment with asenapine. Symptoms of NMS

include "high fever, sweating, unstable blood pressure, stupor, muscular

rigidity, and autonomic dysfunction," according to the National Institute of

Neurological Disorders and Stroke.

Other serious conditions that may occur during treatment with asenapine or

other atypical antipsychotic drugs include hyperglycemia, diabetes mellitus,

and orthostatic hypotension.

The recommended starting dosage of asenapine in adults with schizophrenia is

5 mg taken twice daily. For patients with bipolar disorder, the recommended

starting dosage is 10 mg taken twice daily. If this dosage is not tolerated,

the labeling recommends reducing the dosage to 5 mg taken twice daily.

Asenapine 5- and 10-mg tablets will be sold in 10-tablet blister packs in

boxes of 60 or 100. Each tablet should remain in the blister pack until

needed and then removed with dry hands. The tablet should be placed under

the tongue and allowed to dissolve completely, and the patient should not

eat or drink for 10 minutes after taking the tablet.

The labeling warns against crushing, chewing, or swallowing the sublingual

tablets.

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