• The Food and Drug Administration (FDA) approved combination
olanzapine/fluoxetine capsules (Symbyax) for the acute
treatment of treatment-resistant depression, defined as "major
depressive disorder in adults who do not respond to two separate trials of
different antidepressants of adequate dose and duration in the current
episode," according to an Eli Lilly announcement on March 23.
This is the first drug therapy approved for this indication. The
combination was also approved for depressive episodes associated with bipolar
I disorder in adults. In addition, the individual labels of fluoxetine, which
is currently available in generic form, and olanzapine now contain approved
indications for treatment-resistant depression and bipolar I depression if
each drug is taken in combination with the other. The labels of the
combination drug and olanzapine alone were also revised to contain clinical
trial findings regarding weight gain, hyperglycemia, and increased cholesterol
associated with the antipsychotic.
• The labels of all selective serotonin-reuptake inhibitor
(SSRI) and serotonin- and norepinephrine-reuptake inhibitor (SNRI)
antidepressants were updated in January, as mandated by the FDA, with
warnings about the risk of serotonin syndrome or neuroleptic malignant
syndrome-like reactions. The warning cautions that concomitant use of SSRIs or
SNRIs with monoamine oxidase inhibitors, serotonergic drugs such as triptans
(5-hydroxytryptamine receptor agonists), antipsychotics, or dopamine
antagonists may exacerbate the risk of these potentially life-threatening
adverse events and require careful monitoring.
• The FDA posted changes to the "Warnings and Precautions"
and "Adverse Reactions" sections of the label for
duloxetine delayed-release capsules (Cymbalta) in March. The
updated wording warns of adverse reactions reported in clinical trials and
postmarketing reports. These reactions include tinnitus, poor sleep quality,
polyuria, aggression and anger (particularly early in treatment or after
discontinuation), restless legs syndrome, and other adverse events.
• The FDA's Division of Drug Marketing, Advertising, and
Communications (DDMAC) sent letters to 14 companies requesting that
inappropriate and unlawful drug-promotional Internet links be removed because
they omitted risk information or contained misleading claims. The DDMAC
appears to be stepping up its monitoring and regulation of online drug and
medical-device advertising in recent months. This batch of warning letters
focused on company-sponsored links on Internet search engines that are
intended to draw Internet users to Web sites focused on these drugs, including
duloxetine.
• A proposed settlement of a lawsuit involving paroxetine
extended-release tablets may entitle patients and third-party payers
to reimbursement for buying Paxil CR tablets that were manufactured by
GlaxoSmithKline from April 1, 2002, to March 4, 2005. The lawsuit claimed that
these tablets were defective and tended to split apart. If the proposed
settlement is approved in the final hearing, scheduled for July, the company
will pay up to $28 million to settle claims. The manufacturer has denied any
liability in the suit.
Details of the settlement are posted at<www.simonetpaxilcrsettlement.com>.
• IMS Health and SDI filed a petition with the U.S. Supreme Court on
March 27, seeking to overturn a New Hampshire law that restricts prescription
data mining. Both are large data-gathering companies that collect, analyze,
and sell health care market data, including prescription data that allow
pharmaceutical companies to monitor prescribing patterns of physicians and
other prescribers and identify and target specific prescribers in marketing
efforts. New Hampshire, Maine, and Vermont have passed laws to ban this type
of data mining, but they were struck down or tied up in lower courts based on
First Amendment arguments. However, in November 2008 a federal appellate court
overturned a lower court ruling and upheld the New Hampshire Prescription
Confidentiality Act and in April Vermont's law was upheld in U.S. District
Court.
• Eli Lilly announced inconclusive results from a phase 2 study of
LY2140023, a glutamate mGlu2/3 receptor agonist and a
candidate drug to treat schizophrenia. The finding was somewhat unexpected, as
the compound appeared to be a promising first-in-kind antipsychotic with
positive efficacy data in a previous phase 2a study in 2007.
In this randomized, placebo-controlled trial, 393 patients with
schizophrenia completed four weeks of treatment with LY2140023, olanzapine, or
placebo. The placebo group had an unexpectedly high response rate, according
to the company announcement, and neither olanzapine 15 mg daily nor LY2140023
led to a statistically significant reduction in patients' symptoms compared
with placebo. Lilly said it would continue the clinical development of
LY2140023 and would conduct another phase 2 trial to determine the molecule's
efficacy.
• Cephalon announced positive results from a phase 3 trial of
armodafinil for the treatment of excessive sleepiness in
jet-lag disorder on April 6. An R-enantiomer of modafinil,
armodafinil is currently approved for promoting wakefulness in patients with
excessive sleepiness associated with obstructive sleep apnea/hypopnea
syndrome, narcolepsy, and shift-work sleep disorder.
The randomized, double-blind, placebo-controlled trial was conducted in 427
healthy adults with a history of jet-lag symptoms during the previous five
years. Study participants traveled eastbound from the United States to France
and received either armodafinil or placebo for three days. The drug was
generally well tolerated and was shown to be more effective than placebo in
reducing excessive sleepiness. The company said it would file a supplemental
new drug application with the FDA later this year for this indication.
• A modified-release formulation of eszopiclone, a
nonbenzodiazepine drug currently approved to treat insomnia, failed a phase 2
clinical trial to evaluate its efficacy in patients with generalized anxiety
disorder (GAD), according to a March 5 announcement by its maker Sepracor. In
this 440-patient trial, the drug did not meet the primary endpoint in reducing
the symptoms of GAD.
• Repligen Corp. announced on March 31 that it licensed the patent
rights to the use of uridine to treat bipolar disorder from
McLean Hospital in Belmont, Mass. An oral formulation of uridine is currently
in phase 2 clinical development by the company for treatment of bipolar
depression.
• Switzerland-based Roche and Germany-based Evotec announced a plan to
co-develop a group of compounds that belong to the category of N-methyl
D-aspartate receptor NR2B subtype selective antagonists. These molecules act
on a type of glutamate receptor and may become candidates for treating a
number of central nervous system disorders, including Alzheimer's disease and
Parkinson's disease. One of these drug candidates, EVT 101, is
currently in phase 2 clinical development for treatment-resistant
depression.
• A once-daily formulation of bupropion hydrobromide
extended-release tablets, marketed under the brand name Aplenzin, has
entered the U.S. market, said the manufacturer Sanofi-Aventis on April 7. The
highest dosage form, 522 mg, delivers the equivalent of a 450 mg bupropion
hydrochloride tablet. Approved by the FDA for marketing in April 2008, the
tablet was developed by Biovail and has shown bioequivalence to other
formulations of bupropion tablets.
• Shire announced on March 16 that it has decided to withdraw a
previous application to European regulators to market methylphenidate
transdermal system (Day-trana), a medicated patch approved in the
United States to treat attention-deficit/hyperactivity disorder. The European
authority had asked the company to conduct additional clinical trials.
• A phase 3 study of vilazodone, an investigational
antidepressant developed by Clinical Data Inc., showed positive outcomes in
the treatment of major depressive disorder, according to a study published in
the March Journal of Clinical Psychiatry. In the randomized,
double-blind, placebo-controlled study, 198 patients with depression received
vilazodone and 199 received placebo for eight weeks. The mean
Montgomery-Asberg Depression Rating Scale scores were reduced from baseline by
12.9 points in the vilazodone group and 9.6 points in the placebo group after
eight weeks, and the difference was statistically significant. The reductions
in 17-item Hamilton Rating Scale for Depression scores from baseline were 10.4
points and 8.6 points in the vilazodone and placebo groups, respectively, also
a statistically significant difference. The most frequent adverse events
associated with vilazodone included diarrhea, nausea, and somnolence.
Vilazodone is an SSRI and a partial agonist of the 5HT1A
receptor.
An abstract of "Evidence for Efficacy and Tolerability of
Vilazodone in the Treatment of Major Depressive Disorder: A Randomized,
Double-Blind, Placebo-Controlled Trial" is posted at<www.psychiatrist.com/abstracts/abstracts.asp?abstract=200903/030903.htm>.
• Janssen, a division of Johnson and Johnson, announced on April 1
that results from a clinical trial of paliperidone extended-release
tablets for the treatment of schizoaffective disorder were presented
by the company at the 12th International Congress on Schizophrenia Research in
San Diego. In the randomized, double-blind, placebo-controlled study, 311
patients with acute symptoms were treated with either paliperidone or placebo
for six weeks. The reduction in Positive and Negative Syndrome Scale total
score in the paliperidone group was significantly more than that in the
placebo group. The most common adverse events were headache, dizziness,
insomnia, akathisia, and dyspepsia, according to the company.
Paliperidone is approved to treat schizophrenia. In February Janssen
submitted an application to the FDA seeking approval to use paliperidone to
treat schizoaffective disorder. ▪