SAN DIEGO--(BW HealthWire)--April 13, 1999--Ligand
Pharmaceuticals Incorporated (Nasdaq:LGND) presented today at the
American Association for Cancer Research (AACR) 90th Annual meeting in
Philadelphia results of a pre-clinical study showing Targretin(R)
(bexarotene), when added to tamoxifen therapy, caused complete or
partial regression in 94 percent of tamoxifen-resistant primary breast
tumors.
As a result of the positive indications from multiple
pre-clinical studies, Ligand launched a human Phase II clinical trial
in November 1998 to assess the effectiveness of Targretin capsules in
the treatment of women with advanced breast cancer. Interim results
are expected in the second half of 1999 from this ongoing clinical
trial.
The final analysis of results of the pre-clinical study were
presented yesterday at the AACR meeting by Eric Bischoff, a Ligand
Research Scientist. In June 1998, William W. Lamph, Ph.D., Ligand
Associate Director, Retinoid Research, presented the initial analysis
of this data at the National Surgical Adjuvant Breast and Bowel
Project (NSABP) annual conference in Washington, D.C. Both
presentations were based on data from pre-clinical studies showing
that Targretin caused complete and partial regression of breast cancer
tumors that grew despite tamoxifen therapy. Tamoxifen is currently the
most widely prescribed hormonal breast cancer therapy. Ligand
scientists have previously reported that Targretin does not alter
estrogen, progesterone, or prolactin levels in this scientific model,
and that Targretin can inhibit the undesirable side effects of uterine
growth stimulation that occurs with both estrogen and tamoxifen.
"Our previous studies have shown the efficacy of Targretin in
pre-clinical models for breast cancer prevention and for the treatment
of well-established breast tumors. The additional data presented
yesterday suggest that Targretin may also be a useful therapeutic for
breast cancer patients who have failed tamoxifen therapy," said Dr.
Lamph.
Previously published research (Cancer Research, December 1996)
demonstrated that Targretin and tamoxifen are equally effective in
preventing the emergence of breast cancer tumors in a pre-clinical
model designed to assess tumor prevention. Data from a study reported
in the February 1998 issue of Cancer Research showed that Targretin
caused complete regression in more than two-thirds of established
breast cancer tumors in animal models. In addition, this study showed
that a combination of Targretin and tamoxifen was more effective than
treatment with either agent alone.
Targretin, also known as LGD1069 (bexarotene), a synthetic
retinoid analogue discovered by Ligand scientists, selectively
activates a subclass of retinoid receptors called Retinoid X Receptors
(RXR), which play an important role in the control of cellular
functions.
*T
The data presented yesterday demonstrated that:
-- Targretin, when added to tamoxifen treatment, caused complete
or partial regression in 94 percent of primary breast tumors
that had failed initial tamoxifen therapy. In contrast, only
33 percent of primary breast tumors that remained on high-dose
tamoxifen therapy but did not receive Targretin exhibited a
complete or partial regression. The majority of tumors that
remained on high-dose tamoxifen therapy continued to show
progressive growth, consistent with previous studies showing
emergence of tamoxifen resistance.
-- The combination of Targretin and tamoxifen showed a
significant decrease of 38% in the total number of mammary
tumors per animal compared to only a 6% decrease in total
number tumors per animal for those animals that remained on
tamoxifen therapy alone.
-- The combination regimen of Targretin and tamoxifen not only
reduced the total number of tumors per animal, but also
significantly decreased primary tumor burden by 68%. In
contrast, primary tumor burden increased by 15% for animals
that remained on tamoxifen alone, consistent with their
tamoxifen-resistant characteristics.
-- Targretin, unlike tamoxifen, did not increase the expression
of the estrogen receptor in tumors compared to controls.
*T
In a second paper evaluating the mechanism of action of
Targretin, which was also presented at the AACR meeting, Ligand
scientists reported that treatment of tumors with Targretin in this
animal model altered cellular differentiation in the tumor.
Targretin in Human Clinical Trials
In November 1998, Ligand launched Phase II human clinical trials
of Targretin to treat patients with advanced breast cancer. The
purpose of the study is to assess the efficacy, safety and
tolerability of two dose levels (200 mg/m2 and 500 mg/m2 per day) of
Targretin capsules in up to 180 women with metastatic breast cancer.
The open-label study will be conducted at approximately 30 leading
cancer centers throughout the U.S.
In the breast cancer study, each eligible patient will qualify
for one of three groups (up to 60 patients per group) based on prior
treatment of her disease. The three groups include: patients for whom
standard chemotherapy is no longer effective; patients for whom
standard hormonal therapy is no longer effective; and patients
currently being treated with tamoxifen whose disease has progressed.
The patients included in the tamoxifen-treated group of the study will
remain on tamoxifen and Targretin will be added to their therapy
regimen. Each patient's tumor status will be evaluated every eight
weeks for the first six months of the study and every 12 weeks
thereafter.
Ligand has also studied Targretin for the treatment of patients
with cutaneous T-cell lymphoma, for which Ligand expects to file a new
drug application for Targretin capsules in the first half of 1999, as
well as advanced lung cancer, ovarian cancer, head and neck cancer,
Kaposi's sarcoma, psoriasis and actinic keratoses.
Since 1989, Ligand Pharmaceuticals Incorporated has established a
leadership position in gene transcription technology, particularly
intracellular receptor (IR) technology and Signal Transducers and
Activators of Transcription (STATs) technology. Ligand (pronounced
LY-gand) has applied IR and STATs technology to the discovery and
development of small molecule drugs to enhance therapeutic and safety
profiles and to address unmet patient needs in cancer, women's and
men's health and skin diseases, as well as osteoporosis, metabolic,
cardiovascular and inflammatory disease.
This statement may contain certain forward looking statements by
Ligand 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 Targretin, or any product in the Ligand
pipeline, will be successfully developed, that regulatory approvals
will be granted, that patient and physician acceptance of these
products will be achieved, that results of human clinical trials will
be consistent with any pre-clinical results, or any results will be
supportive of regulatory approvals required to market products. Ligand
undertakes no obligation to update the statements contained in this
press release after the date hereof. |
