This is long but is more objective than yesterdays Dow Jones release. Sorry I can't post a link.
November 16, 1998
Dow Jones Newswires
FDA Panel Backs Ligand's AIDS
Tumor Gel, Panretin
Dow Jones Newswires
By Otesa Middleton
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."
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.
FDA 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
Copyright © 1998 Dow Jones & Company, Inc. All Rights Reserved.
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