Ligand Reports Targretin Causes Regression of Tamoxifen-Resistant Breast
Cancer Tumors in a Preclinical Model
SAN DIEGO, June 16 /PRNewswire/ -- Researchers from Ligand (LYE-gand)
Pharmaceuticals Incorporated (Nasdaq: LGND) have reported that Targretin(R)
(bexarotene), a member of a class of drugs called retinoids, caused regression
of tamoxifen-resistant breast cancer tumors in an established rat model of
this disease. The findings were presented at the National Surgical Adjuvant
Breast and Bowel Project (NSABP) conference in Washington, D.C.
William W. Lamph, Ph.D., Ligand Associate Director, Retinoid Research,
presented, "Beyond Tamoxifen: The Retinoid X Receptor-Selective Ligand LGD1069
(Targretin) Causes Complete Regression of Mammary Carcinoma." The
presentation included new data based on preclinical animal models that show
the efficacy of Targretin in causing complete regression of breast cancer
tumors that are resistant to the drug tamoxifen. Tamoxifen is currently the
most widely prescribed breast cancer therapy.
In the findings presented yesterday, all tumors studied were shown to have
progressed to tamoxifen-resistance prior to randomization. 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. Additional response rate analyses are being
conducted on a total animal tumor burden and number of tumors per animal basis
and are expected to be published in the near future.
"Our previous studies have shown the efficacy of Targretin in preclinical
models for breast cancer prevention, and for the treatment of well-established
breast tumors. The additional data presented today suggest that Targretin may
be a useful alternative to currently available therapies for the treatment of
breast cancer," said Dr. Lamph.
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. Yesterday's presentation also included data from a study reported
in the February 1998 issue of Cancer Research, which showed that Targretin
caused complete regression in more than two-thirds of established breast
cancer tumors. 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 33.3 percent of tumors,
compared to Targretin's rate of complete regression in 72 percent of tumors in
a 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 estrogen and tamoxifen.
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.
"The exciting new data showing the effectiveness of Targretin on
tamoxifen-resistant breast tumors, combined with the activity of Targretin in
treatment and prevention models, and particularly, the evidence of synergistic
activity of low doses of Targretin/tamoxifen, clearly justifies the initiation
of clinical trials with Targretin in breast cancer in different stages of
hormonal responsiveness, including tamoxifen resistance," said Andres Negro-
Vilar, M.D., Ph.D., Ligand Senior Vice President of Research and Chief
Scientific Officer. Ligand plans to launch a Phase II trial with Targretin in
the near future to evaluate the activity of Targretin in advanced breast
cancer patients.
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
gel (bexarotene) 1.0% and two Phase II/III trials with Targretin capsules.
Phase II/III trials are being conducted with Targretin capsules in patients
with advanced lung cancer, and Phase IIb studies are in progress in patients
with ovarian, head and neck cancer and Kaposi's sarcoma. Targretin gel is
also being tested in a Phase II trial for the treatment of patients with
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). 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 disease. |
