Here's the press release:
Ligand Launches Phase II Trial with Targretin Capsules for
the Treatment of Breast Cancer
Business Wire - November 23, 1998 17:31
SAN DIEGO--(BW HealthWire)--Nov. 23, 1998--Ligand (LYE-gand) Pharmaceuticals
Incorporated (Nasdaq:LGND) has confirmed the initiation of a Phase II trial with Targretin(R)
capsules (bexarotene) for the treatment of patients with advanced breast cancer.
The purpose of this open-label 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 patients. The study will
include approximately 30 sites at leading cancer centers throughout the U.S.
The patients will be placed into three groups based on their prior treatment and will include up to 60
patients per group. All groups require that patients have metastatic breast cancer. Eligibility for a
particular group is based on a patient's prior treatment for her metastatic disease. The three groups
include: patients for whom standard chemotherapy is no longer effective; patients for whom standard
hormone 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. All patients will be evaluated every
eight weeks for the first six months of the study and every 12 weeks thereafter.
"We are excited to initiate this trial of a potential new compound for the treatment of advanced breast
cancer," said Steven D. Reich, M.D., Ligand Senior Vice President, Clinical Research. "The
pre-clinical data demonstrate the effectiveness of Targretin on tamoxifen-resistant breast tumors in
animal models, as well as its activity in both treatment and prevention models. We are looking forward
to the treatment options for patients with advanced breast cancer that Targretin may offer."
This year, experts predict that more than 180,000 cases of breast cancer will be diagnosed, making it
the most common non-skin malignancy in the U.S. among women.
George Demetri, M.D., Assistant Professor of Medicine, Harvard Medical School and Dana Farber
Cancer Institute, is the Protocol Chair for the study. "Women with breast cancer are looking for
promising treatment alternatives to chemotherapy. This trial represents the possibility of a translation of
advances in the understanding of breast cancer biology into a new clinical therapy. It is a privilege for
me to collaborate with some of the best cancer centers in the country to offer this potential treatment to
women with breast cancer," Dr. Demetri said.
Preclinical Studies with Targretin And Breast Cancer Tumors
Data presented by William W. Lamph, Ph.D., Ligand Associate Director, Retinoid Research, at the
National Surgical Adjuvant Breast and Bowel Project (NSABP) meeting in May 1998 showed the
activity of Targretin in causing complete and partial regression of breast cancer tumors that are resistant
to the drug tamoxifen based on preclinical animal models. Tamoxifen is currently the most widely
prescribed breast cancer therapy.
The tumors studied were shown to have progressed (after six weeks of tamoxifen therapy) to be
tamoxifen-resistant prior to allocation into treatment groups. Targretin, added to tamoxifen therapy,
caused a complete or partial regression in 94 percent of tamoxifen-resistant primary breast tumors
versus a 33 percent complete or partial regression in tamoxifen-resistant primary breast tumors that
continued on high-dose tamoxifen, but did not receive Targretin. These differences are statistically
significant.
Previous research ("Cancer Research," December 1996) demonstrated that Targretin is equally
effective as tamoxifen at preventing the emergence of breast cancer tumors in this animal model, which
was designed to test 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. The study was the first to compare the treatment potential of
Targretin and tamoxifen both individually and in combination therapy. The use of tamoxifen alone
resulted in complete regression in 33 percent of tumors, compared to Targretin's rate of complete
regression in 72 percent of tumors in this rat breast cancer model. 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 by both estrogen
and tamoxifen.
"We are pleased that the important preclinical observations with Targretin in three different therapeutic
approaches (prevention, treatment, and treatment in tamoxifen-resistant animal models) consistently
showing significant activity are now being translated into a comprehensive clinical trial," said Andres
Negro-Vilar, M.D., Ph.D., Ligand Senior Vice President of Research and Chief Scientific Officer.
Targretin is a synthetic retinoid analogue discovered by Ligand scientists which selectively activates a
subclass of retinoid receptors called retinoid X receptors (RXRs) which play an important role in the
control of cellular function.
Targretin in Clinical Trials
Ligand is conducting three pivotal trials for the treatment of patients with cutaneous T-cell lymphoma,
including one Phase III trial with Targretin(R) gel (bexarotene) 1.0% and two Phase II/III trials with
Targretin(R) capsules. A Phase II trial with Targretin capsules is being conducted for the treatment of
patients with psoriasis. Phase II/III trials are being conducted with Targretin capsules in patients with
advanced lung cancer, and in patients with Kaposi's sarcoma. A Phase II trial with Targretin gel for the
treatment of patients with actinic keratoses and Phase IIb studies in patients with ovarian and head and
neck cancers have been completed.
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). Ligand 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 diseases.
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 that 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.
Note: If you would prefer to receive Ligand's press releases via e-mail please inform us at
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website at ligand.com.
Ligand Pharmaceuticals' releases are available via fax at no charge by calling 888/329-9832 or on the
World Wide Web at www.businesswire.com/cnn/lgnd.htm.
CONTACT: Ligand Pharmaceutical Incorporated
Mary Kenny, 619/550-7536
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