Lilly's Monthly Zyprexa Causes Sleepiness, FDA Says
Eli Lilly %26amp; Cos once-a-month version
of its top-selling antipsychotic medicine Zyprexa, while
effective, has risks that include excessive sleepiness, U.S.
regulators said.
People with schizophrenia taking a monthly injection instead
of daily tablets already on the market may experience “profound
sedation, staff of the Food and Drug Administration said in
documents posted today on the agencys Web site. The sleepiness
is a “serious safety concern because of its severity and
“relatively high incidence, the FDA said.
An FDA advisory panel meets Feb. 6 to consider whether Lilly
should be allowed to sell the monthly Zyprexa. Sales of Zyprexa
tablets, also used to treat bipolar disorder, rose 9 percent to
$4.76 billion last year, accounting for about a quarter of
Indianapolis-based Lillys revenue. The drugmaker is investing in
new and reformulated products because the original Zyprexa may
face generic competition as early as 2011.
“Theres a huge demand, said Jeffrey Lieberman, the
chairman of psychiatry at Columbia University in New York in a
telephone interview. “Even though this is a long-acting form of
an existing drug, its a significant event for the simple reason
that the biggest trouble with treating people with antipsychotics
is adherence to treatment.
Lieberman has consulted for drug companies including Lilly
and Pfizer Inc.
`Particular Concern
Lilly rose 42 cents to $52.08 at 4:35 p.m. in New York Stock
Exchange composite trading. The stock fell 4.6 percent in the
last 12 months.
FDA staff said in December that sleepiness was a
“particular concern with the monthly injection. Sleepiness
occurred in 1.3 percent of patients, todays report said. The FDA
usually follows the advice of its advisory panels, although it
isnt required to do so.
Its possible the sleepiness is caused by doctors
accidentally injecting the medicine into a blood vessel rather
than into muscle, Thomas Laughren, head of the FDA psychiatry
division, wrote in a note prefacing the documents. The sleepiness
may be due to rapid release of the drug, he said.
Lilly proposed labeling that would require one-hour
observation after the shot. The company also suggested patients
not operate machinery and watch for signs of side effects for
three hours. Lilly also proposed a study of 5,000 people to
observe side effects after the drug goes on sale.
`Additional Risk
“We found additional risk that didnt exist with oral
administration, of sedation, said Sara Corya, medical director
for Eli Lilly, in a telephone interview. “Some sedation is a
well-known side effect of Zyprexa in general, as with many
medications.
In an eight-week safety and efficacy study cited by the FDA,
three treatment groups getting the long-acting shot showed fewer
symptoms of schizophrenia starting in the first week than
patients taking a placebo. Patients continued to show better
scores on a common mental-health test throughout the trial.
In another study, the drug stabilized patients mental
health over 24 weeks, according to the data.
Zyprexa is already available in a short-acting injection
that takes effect in 15 to 45 minutes. That version wears off in
about the same time as the once-daily pill, according to labeling
approved by the FDA.
Zyprexa is in a family of medicines, introduced in the last
decade, known as atypical antipsychotics. They are designed to
cause fewer neurological side effects that made users of earlier
drugs tremble, doze and jerk involuntarily.
Johnson %26amp; Johnsons Risperdal, also an atypical
antipsychotic, already comes in an injection given every two
weeks, called Consta. Risperdal, J%26amp;Js top-seller, generated $4.2
billion in 2006.
Doses Appeal
“The growth of Risperdal Consta shows the appeal of an
infrequently dosed schizophrenia medicine, said Michael
Krensavage, an analyst at Raymond James, in a telephone
interview. “Theres certainly an advantage to keeping people on
their medicine.
Consta sales were $1.1 billion in 2007, according to
Krensavages estimate. He projects $1.4 billion sales this year.
“The once monthly dosing of Zyprexa is an advantage over
twice monthly, thats obvious, Krensavage said. “Theres
probably a place in the market for both.
Two other drugs, haloperidol and fluphenazine, are also
approved in long-acting injections. Both belong to an older class
of antipsychotics.
More than 1 percent of the worlds population has
schizophrenia, including about 2 million Americans, according to
the U.S. Centers for Disease Control and Prevention.
Brain Targets
In a pilot study of 14 patients already taking Zyprexa,
doctors led by David Mamo of the University of Toronto found that
the monthly Zyprexa injection hit its targets in the brain. Half
the patients he studied needed Zyprexa tablets as supplements
during the six-month study.
The most common side effects of the injection were insomnia,
aggravated psychosis and anxiety, said the study, published on
the Internet in April, 2007, by the journal
Neuropsychopharmacology.
Lilly expects to finish a study comparing the tablet with
the injection around June 2009, according to information
published on clinicaltrials.gov, a Web site run by the U.S.
National Institutes of Health.
Diabetes Concerns
Zyprexa pills were approved by the FDA in 1996 to treat
schizophrenia and bipolar disorder. Lilly added new warnings in
October 2007 on the risk of weight gain and elevated sugar and
fat in the blood. Lawsuits have been filed against the company
alleging that the drug caused diabetes and other illnesses.
Lilly agreed to settle 950 Zyprexa claims, averting what
would have been the first U.S. trial next month. The company
faces an additional 1,100 lawsuits. Patient groups have faulted
Lilly for improperly warning of side effects. The drug also is
prescribed for children.
“The issue was that they were downplaying weight gain and
metabolic effects, said Lieberman, the Columbia professor.
“Thats known now.
Information on weight gain has been in Zyprexas prescribing
literature from the beginning, and Lilly provides information to
the FDA as it becomes available, company spokeswoman Tarra Ryker
said today in a telephone interview.
Lilly said last month it received a subpoena in November
from a U.S. grand jury in Pennsylvania seeking documents related
to its marketing of Zyprexa. The New York Times, citing sources
it didnt identify, said Lilly may pay more than $1 billion to
settle federal and state investigations into whether the company
promoted the drug for uses not approved by the FDA.
The Times report contained “many speculative statements,
Lilly spokeswoman Marni Lemons said in an e-mail on Jan. 31.
