By Laura Gilcrest
WASHINGTON, Jul 20 (Reuters Health)- The Psychopharmacological Drugs
Advisory Committee to the US Food and Drug Administration (FDA) voted on
Wednesday to recommend that the agency approve Pfizer's Zeldox (ziprasidone) for
the treatment of schizophrenia.
The panel's recommendation comes after Pfizer's second bid before the
committee, which rejected the product 2 years ago based on concerns regarding
the drug's causal link to a potentially fatal abnormal heart rhythm.
The FDA usually follows the advice of its advisory panels.
Specifically, Zeldox, like other drugs in its class, has been shown to
prolong the patient's cardiac interval, or QT on an electrocardiogram, a
condition that can lead to cardiac fibrillation, and in turn, to serious cardiac
arrhythmia. QT prolongation is particularly an issue when the patient is also
taking other drugs, such as antihistamines. With that risk in mind, the
committee attached several caveats to their recommendation, including that
Zeldox's labeling adequately reflect its propensity to affect the heart rhythm
and that Pfizer conduct further studies to more fully assess its product's
health risks.
For example, several panelists advised that Zeldox's labeling clearly warn
that it should not be used with other drugs also known to prolong the cardiac
interval. Other panel members recommended labeling that reflects the lack of
current data regarding Zeldox's risks at doses exceeding 160 mg.
The panel further requested that Pfizer design postmarket studies to
evaluate Zeldox's overall mortality risks, treatment adherence by patients, and
its implications in the elderly and pediatric populations.
In addition, the panel advised the company to conduct more tests on the drug
in patients using other medications commonly prescribed to Zeldox's target
population, such as anti-depressants, mood enhancers, beta blockers and calcium
channel blockers. The committee agreed, however, that a black box warning or
limiting Zeldox to a second line treatment was not necessary.
Pfizer collaborated with the FDA on a study to assess the magnitude of
Zeldox's QT effect. The study involved 183 volunteers, average age 37, who
suffered from chronic schizophrenia. Of those participants, 75% of whom were
male, 164 subjects completed the study.
Data generated from the study and from four previous short-term trials
showed that Zeldox prolonged the QT by six to ten milliseconds, on average, at
80 mg to 200 mg daily dosage. The drug also demonstrated a 15 to 20 milliseconds
prolongation at the maximum dose concentration of 160 mg dose per day.
The drug showed no significant cardiovascular events and no increase in the
risk of fainting or sudden unexpected deaths among trial participants. In fact,
Zeldox was shown to have a positive effect on certain cardiac risk factors, such
as body mass index (BMI) and blood lipid and glucose levels.
In pressing their case for approval, Pfizer representatives strongly
emphasized to the panel an "unmet medical need" for the product. For example, of
the approximately 3 million people in the US afflicted with schizophrenia, 20%
to 30% respond poorly to current therapies, Pfizer's global research and
development director, Dr. Edmund Harrigan, said.
Harrigan noted that the yearly relapse rate is 70% among untreated patients
and 20% among treated patients. The company claims that one of Zeldox's benefits
is relapse prevention.
The FDA's approval of Zeldox will have significant revenue implications for
the New York-based pharmaceutical company. Pfizer estimates that the drug,
launched into a marketplace growing at a 20% annual rate, could potentially net
the company up to $1 billion per year.
Len Yaffe, a securities analyst with Banc of America Securities has
predicted that Zeldox sales would reach $400 million next year and $700 million
in 2002.
Competing antipsychotic drugs include Lilly's Zyprexa, which generated $458
million in first quarter sales this year, Johnson & Johnson's Risperdal and
AstraZeneca's Seroquel. Bristol-Myers Squibb also has a schizophrenia drug in
the pipeline.
