Dow Jones article:
WASHINGTON (Dow Jones)--A federal panel backed Ligand Pharmaceuticals Inc.'s
(LGND) first drug Monday, its Panretin gel for treating skin lesions on
patients with AIDS-related Kaposi's sarcoma.
The U.S. Food and Drug Administration will consider the panel's
recommendation when it decides whether or not to approve the drug. The agency
usually heeds the advice of the expert panels it convenes.
Ligand is asking for Panretin's approval as a primary treatment to be used
two to four times daily. However, the panel said it wouldn't recommend
classifying it as a first-line treatment. The drug's active ingredient is a
derivative of vitamin A.
The FDA is reviewing Panretin on an expedited basis, because it treats a
serious or life-threatening disease and it may be an improvement in the way the
condition is treated. Panretin also has been classified as an orphan drug,
which will give Ligand incentives to develop it because it would treat an
ailment that affects less than 200,000 people in the U.S. Ligand estimates that
between 30,000 and 50,000 patients in the U.S. and Western Europe have the
disease.
If approved, Panretin, a gel applied directly to skin lesions, will be the
first local treatment patients can apply at home.
Ligand presented the panel with the results of its two efficacy trials. One
trial, conducted at 35 sites, of 268 patients in the U.S. and Canada, found 35%
of Panretin patients responded, compared to 18% of those treated with an
inactive, placebo, gel.
The second trial, with 134 patients, conducted in 22 sites in the U.S.,
Europe and Australia, found 37% of patients treated with Panretin responded,
compared to 7% of placebo patients. That study was stopped early because an
independent board determined that efficacy was proven when an established level
of response was reached.
Response was determined by patients as well as their physicians.
During its presentation, Ligand said it disagreed with FDA reviewers, who
also presented their assessment of the company's study findings.
Dr. Richard C. Yocum, senior medical director at Ligand, said the FDA
reviewers looked at photographs of lesions to determine whether the patients
responded to Panretin.
Based on these pictures, Yocum said, FDA reviewers called many patients
nonresponders whom Ligand considered responders.
However, Yocum said, photos weren't standardized because different films and
cameras were used. Also, he said height and color of lesions can't be
well-defined by looking at before and after photographs.
"Photographs are inferior to direct, hands-on evaluations," Yocum said. "Some
patients' own assessments disagreed with the FDA."
(MORE) DOW JONES NEWS 11-16-98
12:43 PM
Dr. Barbara L. Melosky, head of the Kaposi's sarcoma tumor group at the
British Columbia Cancer Agency, was an investigator at one of the Panretin
study sites where 28 patients were treated.
"Lesions got flatter, lighter and smaller. Some completely responded,"
Melosky said. "Patients were extremely satisfied."
An Australian study investigator, Dr. Neil J. Bodsworth, said that after
lesions responded, he saw no evidence of relapse. Bodsworth also told the panel
Panretin seemed to work at the same rate regardless of patient's stage of HIV
or HIV therapy.
The studies found the most common side effects to be skin irritation, redness
and pain where Panretin was applied.
The company said Panretin worked on patients who had failed to respond to
other Kaposi's Sarcoma treatments and on those who were taking other HIV drugs.
Richard van den Broek, a biotechnology analyst at Hambrecht & Quist, said he
projects that if Panretin ultimately is approved, it will be a "modest seller,"
with sales under $50 million.
Van den Broek said advancements in terms of AIDS treatments has reduced the
demand for drugs like Panretin.
More than a century ago, Kaposi's sarcoma was first described by
Austro-Hungarian dermatologist Moritz Kaposi. The disease was rarely seen
before HIV and AIDS, according to a Ligand release. Kaposi's sarcoma usually
involves widespread tumors on the skin or in the mouth, lymph nodes or inner
organs.
Kaposi's sarcoma was described to the panel by Dr. Stephen A. Miles,
associate professor at the University of California at Los Angeles' division of
hematology and oncology.
HIV-positive people are 40,000 times more likely to develop the ailment than
those who aren't infected with the virus that causes AIDS, Miles said.
About 9% of all new AIDS patients have Kaposi's sarcoma.
(MORE) DOW JONES NEWS 11-16-98
12:46 PM
reviewer Dr. Robert White told the panel that Panretin's benefits can't
be compared to those of an internal treatment, which attacks the disease and
not just the visible lesions.
When FDA panels review therapies, the company and FDA reviewers present
assessments of the study data. Then the panel votes on whether or not to
recommend approval of the product.
White said the FDA asked Ligand for photos of patients' lesions to help the
agency review the Panretin application.
Based on the pictures, White said, the FDA reviewers disagreed with Ligand's
assessment of some patients as Panretin responders. The FDA reviewers disagreed
with half of the patients Ligand considered responders.
White also said Ligand's two Panretin studies had different criteria.
One study required patients have at least six lesions, with at least three of
those raised. In that study, body photos were taken of all participants.
The other trial, which the FDA reviewers said was less rigorous, required
only three raised or flat lesions for studying. The trial didn't require global
body photos.
The frequency with which the medicine was applied also differed between
studies, White said.
When the panel discussed Panretin, panelist Dr. James Krook said he didn't
see evidence to recommend the drug as a first-line, or first-option, therapy.
"I would leave it up to the clinician, whether it will be the first, second,
third or fourth treatment," Krook said.
Some committee members were concerned because Panretin treated only the skin
lesions themselves, but not the actual Kaposi's sarcoma ailment.
However, E. Carolyn Beaman, the panel's consumer representative and president
of Sisters Breast Cancer Network in Lake Jackson, Texas, said if the drug has
an aesthetic and psychological benefit, it is worth approving.
-Otesa Middleton; 202-862-6654
(END) DOW JONES NEWS 11-16-98
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