Ligand's Targretin Prevents Development of Mammary Tumors in Pre-Clinical Study of ER-Negative Breast Cancer, Journal Article Reports
Monday December 9, 6:35 pm ET
SAN DIEGO--(BUSINESS WIRE)--Dec. 9, 2002--Ligand's approved cancer drug Targretin® (bexarotene) dramatically reduced the development of estrogen receptor (ER)-negative mammary tumors in mice that were genetically modified to develop breast cancer, according to an article published by Baylor College of Medicine and Ligand researchers in the peer-reviewed journal Cancer Research (62, 6376-6380, 11/15/02).
"In this study, Targretin effectively suppressed the development of ER-negative mammary tumors in mice with minimal toxicity," said senior author Powel H. Brown, MD, PhD, from the Baylor College of Medicine. "The study suggests that Targretin may be a promising agent for the prevention of breast cancer, and may be particularly useful in preventing ER-negative breast cancer. Despite the effectiveness of selective estrogen receptor modulators (SERMs) in preventing ER-positive breast cancer, new chemopreventive agents are urgently needed for the prevention of ER-negative disease."
In the study, "The Retinoid X Receptor-Selective Retinoid, LGD1069, Prevents the Development of Estrogen Receptor-Negative Mammary Tumors in Transgenic Mice," the researchers used an established mouse model for human, ER-negative breast cancer in which transgenic mice over-express the erbB2 gene, leading to the development of mammary carcinoma. From three to 17 months of age, the mice were treated daily, for six days a week, with a control vehicle, Targretin at 10 mg/kg of body weight, or Targretin at 100 mg/kg. Tumors were measured twice a week, and symptoms of toxicity were recorded daily.
Two outcome measures were evaluated: the age of mice when a tumor first appeared, and the total number of tumors occurring in each animal until 17 months of age. Efficacy results, which the authors attribute primarily to Targretin's anti-proliferative activity, were:
Median days % of mice Number of
to tumor with tumors at tumors per
development study end mouse
Sesame oil
(control arm) 234 100% 1.4+/-0.6
Targretin 10 mg/kg 321 74% 0.9+/-0.7
Targretin 100 mg/kg Not reached 24% 0.2+/-0.4
(greater than
416 days
of treatment)
The delay in time to tumor development was statistically significant (P less than 0.0001 by the Generalized Wilcoxon test), as was the difference in the total number of tumors between the control and high-dose groups (P less than or equal to 0.001 by ANOVA).
The authors note that Targretin caused fewer side effects than other retinoids because it is the only drug that binds selectively to retinoid X receptors. In this study, mice that received Targretin showed a slight increase in weight, and none of the mice in the control or low-dose Targretin arms developed any signs of toxicity. Toxicities from high-dose Targretin were mild and occurred only after an average of 205 days of treatment. These side effects included hair loss and ear skin irritation in up to 46% of treated animals.
"These encouraging early results add to the impressive body of preclinical and clinical evidence illustrating the potential of Targretin to treat solid tumors," said Andres Negro-Vilar, MD, PhD, Ligand's senior vice president for research and development and chief scientific officer. "We continue to explore opportunities to elucidate Targretin's potential benefit in breast cancer."
A 100-patient Phase II study is underway at Baylor and three other institutions in Texas -- MD Anderson, the University of Texas Health Science Center at San Antonio, and the University of Texas Southwestern University -- to evaluate Targretin as a chemopreventive agent in women at high risk of breast cancer. The study is being sponsored by the National Cancer Institute.
About Breast Cancer and Previous Targretin Studies
The American Cancer Society estimates that about 200,000 new cases of breast cancer will be diagnosed in the United States in 2002, and that the disease will cause 40,000 deaths. Approximately 25-30% of breast cancer cases are of the difficult-to-treat ER-negative variety. ER-negative breast cancer is often treated with radiation, chemotherapy and surgery, since it does not respond to hormone therapy.
In March of 2001, Ligand announced results of a Phase II study of Targretin for the treatment of metastatic breast cancer in patients whose disease had progressed while they were taking other therapies. Unlike the pre-clinical prevention study published in Cancer Research, most of the patients enrolled in the earlier, treatment-focused clinical trial had ER-positive breast cancer. Although a number of advanced-stage patients appeared to benefit from treatment with Targretin, the overall objective tumor response did not meet the protocol-defined target for activity in this patient population.
About Targretin Capsules
In December 1999, the U.S. Food and Drug Administration (FDA) granted marketing approval for Targretin capsules with once-daily oral administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy.
Full prescribing information for Ligand's products can be obtained in the United States from Ligand Professional Services by calling 800-964-5836, or on Ligand's internet site at www.ligand.com.
About Ligand
Ligand Pharmaceuticals Incorporated discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, skin diseases, men's and women's hormone-related diseases, osteoporosis, metabolic disorders, and cardiovascular and inflammatory diseases. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IRs) and Signal Transducers and Activators of Transcription (STATs).
Caution Regarding Forward-Looking Statements
This news release may contain certain forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Actual events or results may differ from Ligand's expectations. There can be no assurance that results of subsequent studies of Targretin, alone or in combination with any therapy, will confirm results presented here. Additional information concerning these and other risk factors affecting Ligand's business can be found in prior press releases as well as in Ligand's public periodic filings with the Securities and Exchange Commission, available via Ligand's internet site at www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.
Ligand Pharmaceuticals' releases are available on the World Wide Web at www.businesswire.com/cnn/lgnd.htm.
--------------------------------------------------------------------------------
Contact:
Ligand Pharmaceuticals Incorporated
Michael Watts, Director, investor relations and
corporate communications, 858/550-7850
--------------------------------------------------------------------------------
Source: Ligand Pharmaceuticals Incorporated |
