• The Food and Drug Administration (FDA) is requiring manufacturers to
add a precaution on the labels of all antipsychotics about the
risks of leukopenia, neutropenia, and agranulocytosis associated with the
entire drug class. These adverse events related to white-blood-cell counts
have been reported to the agency in clinical trials or postmarketing reports.
Patients with an already low white blood-cell count and a history of
drug-induced leucopenia/neutropenia may be at a higher risk for developing
such problems if they are taking antipsychotics. Clinicians should carefully
monitor patients for symptoms of infection if neutropenia develops and
discontinue the drug if neutrophil count falls below 1000/mm3. The
labeling change applies to both first- and second-generation
• The FDA and the European Medicines Agency have launched a
collaborative initiative to share standards and information for the regulation
of clinical-trial practices, the FDA announced on August 3. The initiative
includes sharing the agencies' reports from routine inspection and monitoring
of clinical-trial sites, streamlining procedures, and communicating regulatory
legislation and guidelines with each other. As more pharmaceutical and
medical-device companies conduct global trials and seek marketing approval
with clinical data collected abroad, the two agencies hope to share the
inspection resources in monitoring compliance and assessing ethical conduct of
• The FDA approved paliperidone extended-release oral
tablets for acute treatment of schizoaffective disorder as either monotherapy
or adjunctive therapy to mood stabilizers and/or antidepressants, according to
a July 31 announcement by Ortho-McNeil-Janssen Pharmaceuticals, a subsidiary
of Johnson and Johnson. Two randomized, double-blind, placebo-controlled
trials were conducted in patients with schizoaffective disorder for six weeks
to support the approval.
In these trials patients either received paliperidone alone or were given
paliperidone along with a mood stabilizer with or without an antidepressant.
Patients on a dosage of 12 mg/day (with the option of reducing to 9 mg/day) of
paliperidone showed statistically significant improvement over placebo
patients on Positive and Negative Syndrome Scale (PANSS) total scores. A lower
dosage (6 mg/day with the option of reducing to 3 mg/day) did not achieve
significant difference in PANSS total score between the active treatment and
placebo groups. Paliperidone had already been approved for acute and
maintenance treatment of schizophrenia. It is currently the only medication
carrying the approved indication for schizoaffective disorder.
The approved prescribing information for paliperidone tablets is
• The FDA has approved the once-monthly, long-acting formulation of
paliperidone palmitate injection for acute and maintenance
treatment of schizophrenia, Ortho-McNeil-Janssen announced on August 4. The
approval was based on four short-term clinical studies and one long-term study
in which paliperidone palmitate was compared with placebo. In this
formulation, paliperidone comes in prefilled syringes, and the first two
intramuscular injections should be administered one week apart, followed by
monthly injections thereafter. The company also manufactures risperidone
long-acting injection, which is dosed once every two weeks. On August 27
Johnson and Johnson announced its decision to terminate the development of a
once-every-four-week formulation of risperidone.
The approved prescribing information for paliperidone palmitate
injection is posted at<www.invegasustenna.com/invegasustenna/shared/pi/invegasustenna.pdf>.
• The FDA has approved guanfacine extended-release
tablets for the treatment of attention-deficit/hyperactivity disorder (ADHD)
in children and adolescents aged 6 to 17, Shire announced on September 3. Also
used to treat hypertension, guanfacine is an alpha2A adrenergic
receptor agonist. Shire developed this once-daily formulation specifically for
the treatment of ADHD. The product, which is being marketed under the brand
name of Intuniv, will not be a controlled medication.
In two randomized, double-blind, placebo-controlled clinical trials,
children and adolescents treated with guanfacine improved in ADHD Rating
Scale-IV total scores from baseline, and the difference between the active
drug and placebo was statistically significant. The most common adverse events
seen in the trials included somnolence, headache, fatigue, upper abdominal
pain, and sedation. Adverse effects related to alpha agonists, such as
hypotension, bradycardia, and syncope, were also observed in some patients.
Prescribers are urged to assess patients' heart rate and blood pressure before
starting the medication, followed by periodic monitoring.
• Labopharm Inc., a Canadian company, said on August 25 that the FDA
accepted its response to a previous letter the agency had issued regarding the
company's trazodone extended-release tablets, a once-daily
formulation of the first-generation antidepressant developed by the company
and currently awaiting FDA marketing approval. According to the company, the
agency's letter had initially rejected the new drug application because of
deficiencies discovered at a manufacturing plant but cited no safety or
efficacy concerns about the medication. A final decision on the application
will be made by February 2010.
• Dainippon Sumitomo Pharma, a Japanese pharmaceutical company,
announced on August 26 positive results from a phase 3 clinical trial of
lurasidone, a second-generation antipsychotic in development.
Lurasidone binds to dopamine D2, serotonin 5-HT7,
5-HT2A, 5-HT1A, and noradrenalin alpha2c
receptors. In the randomized, double-blind, controlled trial, 478 patients
with schizophrenia were given lurasidone 40 mg/day or 120 mg/day, placebo, or
olanzapine 15 mg/day for six weeks. Olanzapine was included as an active
comparator to determine whether the trial was conducted with enough
sensitivity to be able to detect a difference between active treatment and the
At both dosage levels, lurasidone was more effective in reducing patients'
psychotic symptoms as measured by the PANSS total score. Lurasidone did not
beat olanzapine in the primary efficacy endpoint. The most common adverse
events associated with lurasidone were akathisia, somnolence, sedation,
extrapyramidal effects, nausea, and dystonia. The median weight gain after the
six-week study was 0.9 kg in the 40 mg/day lurasidone group, 0.5 kg in the 120
mg/day group, 0 kg in the placebo group, and 3.1 kg in the olanzapine group.
The company said it plans to file a new drug application for lurasidone with
the FDA in early 2010.
• The investigational drug pimavanserin, which is
being studied for Parkinson's disease psychosis, failed to meet the primary
efficacy endpoint in a phase 3 trial conducted by its maker, Acadia
Pharmaceuticals, according to a September 1 company announcement. In a
double-blind, placebo-controlled trial, 298 patients diagnosed with psychosis
related to Parkinson's disease were randomly assigned to pimavanserin 10
mg/day or 40 mg/day or to placebo. After six weeks of treatment, symptoms
improved from baseline in all three groups, as indicated by the Scale for the
Assessment of Positive Symptoms (SAPS) score. The SAPS score decreased by 5.8
points and 6.7 points in the pimavanserin 10 mg and 40 mg groups,
respectively. Neither change differed significantly from the 5.9-point
reduction in the placebo group.
Pimavanserin is a serotonin 5-HT2A receptor inverse agonist
being developed for psychosis associated with Parkinson's and Alzheimer's
diseases. The company said it plans to continue the phase 3 development.▪