V1, HENRY, SQUELCHERS(TM) AND ALL YOU OTHER LGND LOVERS, feast your eyes on this delightful tidbit below. While the market for KS is not that large, this looks like the first commercial validation of LGND's technology. Of course FDA approval remains to be secured, but these results are HOT!!! Who knows, maybe Henry is right about LGND leading the sector higher?
News Alert from PR Newswire via Quote.com
Topic: Ligand Pharmaceuticals 'B'
Quote.com News Item #3813720
Headline: International Panretin(TM) Topical Gel Trial Demonstrates Positive
Results in Kaposi's Sarcoma; Study Stopped Per Protocol at Interim Analysis of
Results
======================================================================
SAN DIEGO, Aug. 26 /PRNewswire/ -- An international Phase III pivotal
trial of Panretin(TM) (9-cis-retinoic acid) Topical Gel in patients with AIDS-
related Kaposi's sarcoma (KS) has been stopped early because an interim
analysis permitted under the protocol showed a marked response to Panretin
compared with placebo (vehicle gel with no Panretin). Of 82 patients included
in the interim analysis, forty-two percent (42%) on Panretin Topical Gel
achieved complete or partial response versus only seven percent (7%) response
of patients on placebo, a result that was statistically significant at a
"p value" of 0.00027.
"The protocol had a provision that permitted early stopping of the trial
prior to full patient enrollment if the treatment with Panretin Topical Gel
was clearly beneficial to patients," according to Marvin E. Rosenthale, Ph.D.,
President of Allergan Ligand Retinoid Therapeutics, Inc. (ALRT)
(NASDAQ:ALRI).
"These positive interim results are the first confirmation of those
obtained in earlier Phase I/II studies," according to John R. Gibson, Ph.D.,
Allergan Senior Vice President of Development.
This international trial, conducted by Allergan, Inc. (NYSE:AGN) in
Europe, Australia and the United States, is the second of two Phase III
pivotal trials of Panretin(TM) Topical Gel in KS patients, which have been
launched under a U.S. Investigational New Drug (IND) application on behalf of
ALRT. Patient accrual is now complete for a North American Phase, III pivotal
trial of similar design conducted by Ligand Pharmaceuticals Inc.,
(Nasdaq: LGND). The results of this trial are expected in the fourth quarter
of 1997.
ALRT expects that both Phase III trials could be used in the filing of a
U.S. New Drug Application (NDA) later this year or early next year, though the
international Phase III trial was not originally scheduled to be part of the
U.S. NDA. Panretin Topical Gel would be the first topical product to be
submitted to the FDA in this disease.
Study Design
Both Phase III trials are randomized, double-blind, placebo-controlled 12-
week studies of topical 9-cis-retinoic acid gel (Panretin(TM)) in the
palliative treatment of cutaneous AIDS-related KS. The objectives of the
trials are to compare the efficacy of 0.1% Panretin Topical Gel to placebo
when applied topically and to determine the safety and tolerability of the
formulation in this patient group. Palliative treatment means alleviation of
cutaneous lesions, in this case reduction in the size or number of KS lesions
on the skin as per AIDS Clinical Trial Group (ACTG) criteria as applied to
topical therapy.
Methodology
The protocol for the Phase III trial conducted by Allergan on behalf of
ALRT calls for patients to be treated with either a 0.1% gel formulation of
Panretin(TM) or placebo vehicle gel, applied twice daily to cutaneous KS
lesions for 12 weeks. It was expected that approximately 270 patients would
be required to be enrolled based on estimates of a response rate of 25% in the
Topical Panretin treatment arm and up to 10% in the placebo arm.
The international trial, conducted at 30 centers, was initiated in
September of 1996 and was designed with an interim analysis which would permit
its early conclusion if a significant number of patients were receiving clear
benefit from Panretin Topical Gel treatment.
The protocol stated:
"If there is a large benefit for the active treatment it will be important
to stop the trial early. Therefore one interim analysis will be undertaken.
If the results show a clear benefit for the active treatment they may be
submitted to European Regulatory Authorities for early Product Registration."
The interim analysis compared the response rates of the two treatment
groups statistically to determine if the level of significance ("p value") was
0.005 or less. If that level of significance had not been reached, the trial
would have continued to 270 patients as originally planned. However, the
level of significance, "p value" of 0.00027 was reached triggering an early
stop as permitted by the protocol.
Results
Of 82 patients with biopsy confirmed KS, 36 received therapy with 0.1%
Panretin(TM) Topical Gel and 46 were treated with placebo (vehicle gel with no
active drug). Patients were seen for assessment at 2, 4, 8 and 12 weeks after
trial entry and responses were defined using ACTG criteria applicable to
topical therapy. After 12 weeks, patients could be enrolled in a separate
open label protocol and be treated with Panretin Gel for up to nine additional
months.
Forty-two percent (42%) of patients treated with Panretin Topical Gel had
a complete or partial response as compared with 7% of patients treated with
placebo.
Because the required level of significance in response was achieved, ALRT
determined that Panretin Gel was active in the trial and new patients should
no longer be enrolled. Patients currently enrolled in the Allergan sponsored
trial of Panretin Topical Gel will continue with their assigned treatment and,
upon completion of the "blinded" phase, be allowed to enroll in the "open
label" trial which provides Panretin Topical Gel to all the patients in the
trial without comparison to placebo.
In the U.S. Phase III pivotal trial of Panretin Topical Gel in KS
sponsored by Ligand, patient accrual is complete and the treatment and follow-
up evaluation of 268 patients is ongoing. ALRT does not expect the positive
results in the international trial to significantly interfere with the U.S.
trial patient follow-up now underway.
"While the results in the Allergan-sponsored international study are quite
dramatic, we will continue each patient's assigned treatment in both the
Ligand-sponsored and Allergan-sponsored studies through completion of the
blinded phase," according to Dr. Rosenthale. "We expect to be able to analyze
and announce the final results of the North American Phase III trial early in
the fourth quarter of this year, and if the results are positive, to file an
NDA within two to three months," Dr. Rosenthale said.
Panretin(TM) Oral Capsules are also being studied in patients with AIDS-
related Kaposi's sarcoma. Other studies are ongoing in breast, ovarian and
prostate cancer and a study in severe plaque psoriasis has been completed.
ALRT expects to be able to determine additional indications for NDA filing
from these studies based on results ALRT expects to announce later this year
or early in 1998. Oral Panretin is also in Phase III pivotal trials in
patients with acute promyelocytic leukemia (APL).
Panretin is a proprietary product of Allergan Ligand Retinoid
Therapeutics, Inc., a company whose primary purpose is to discover and develop
drugs based on retinoids. Retinoids have a broad range of biological actions,
and evidence suggests that retinoids may be useful in the treatment of skin
diseases, metabolic diseases, a variety of cancers, including certain forms of
leukemia, as well as eye diseases.
This statement may contain certain forward looking statements by ALRT and
actual results could differ materially from those described as a result of
factors including, but not limited to, the following. There can be no
assurance Panretin, or any product in the ALRT pipeline, will be successfully
developed, that regulatory approvals will be granted, that patient and
physician acceptance of these products will be achieved, that final results of
human clinical trials will be consistent with any interim results, or that
final results will be supportive of regulatory approvals required to market
products. ALRT undertakes no obligation to update the statements contained in
this press release after the date hereof.
SOURCE Allergan Ligand Retinoid Therapeutics, Inc.
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