Here's the press release that launched this thread:
Ligand Reports On New Indications For Targretin(TM) (LGD1069)
Preclinical studies in mouse models indicate RXR-selective retinoid may have
utility in treatment of diabetes and prevention/treatment of breast cancer
SAN DIEGO, Sept. 12 /PRNewswire/ -- Scientists from Ligand Pharmaceuticals
Inc. (Nasdaq: LGND) today reported preclinical study results at the Bear
Stearns conference in New York that indicate Targretin(TM) (LGD1069), one of
Ligand's lead retinoid therapeutics, may have utility in treating human type
II diabetes and in the treatment or prevention of breast cancer. The
preclinical data demonstrated Targretin's (LGD1069) ability to significantly
decrease blood glucose, triglyceride and insulin levels in mouse models of
human type II diabetes and human obesity. In addition, in a rat model of
mammary carcinoma, Targretin (LGD1069) reduced incidence and tumor frequency
at least as well as tamoxifen, without the undesirable reduction in mean body
weight produced by tamoxifen.
"The ability of Targretin (LGD1069) to provide therapeutic benefits in
preclinical animal models of diabetes and breast cancer reinforces the concept
that retinoid-based drugs may play a major role in treating a variety of
diseases susceptible to intervention through intracellular signaling
pathways," according to Andres Negro-Vilar, MD, Ph.D., Ligand Senior Vice
President, Research, and Chief Scientific Officer. "We will evaluate
Targretin (LGD1069) for treatment of these new indications because they
address the needs of large patient populations with few optimal therapeutic
alternatives."
Commenting on data presented at the conference, Dr. Richard Heyman, Ligand
Director, Retinoid Research, explained: "Our molecular approach to drug
discovery, coupled with our extensive understanding of retinoid action, has
led us to the identification of an unexpected and novel class of compounds
that have promise in new indications."
Preclinical Data In db/db and ob/ob Mouse Models of Diabetes
Data presented by Dr. Heyman indicate Targretin(TM) (LGD1069) may be
useful in the treatment of human type II diabetes. Using two mouse models of
human type II diabetes (the db/db mouse, and the ob/ob mouse), Targretin
(LGD1069) was compared to treatment with a thiazolidinedione (TZD), a member
of a new class of investigational antidiabetes drugs, and a control group (15
animals in each treatment group). Animals were treated daily at 3 doses for
14 consecutive days, and glucose, triglycerides and insulin levels were
monitored throughout the duration of the treatment.
* Targretin (LGD1069) significantly decreased the levels of blood glucose
by 40%, triglycerides by 30% and insulin by 20%, at the termination of the
study.
* Targretin (LGD1069) maintained the antidiabetic activity during the
course of therapy.
* Targretin (LGD1069), as a single agent, was as effective as TZD.
* Targretin (LGD1069) demonstrated additive therapeutic effects when
administered with TZD.
* Targretin (LGD1069) was well tolerated throughout the treatment period.
Non-insulin dependent diabetes mellitus (NIDDM or type II diabetes) is a
metabolic disorder affecting primarily adult individuals and is characterized
by profound changes in glucose homeostasis and a cascade of associated
hormonal and metabolic disturbances. Elevated levels of glucose
(hyperglycemia) and triglycerides (hypertriglyceridemia) as well as increases
in insulin (hyperinsulinemia) levels due, at least in part, to the ensuing
insulin resistance are part of the metabolic profile seen in these patients.
Targretin (LGD1069) acts as an insulin sensitizer leading to a significant
reduction in hyperglycemia, hypertriglyceridemia and hyperinsulinemia in
animal models of NIDDM.
"This suggests that these agents may be effective in the treatment of type
II diabetes," according to Dr. Heyman. "Since a key event in the actions of
Targretin (LGD1069) is the activation of RXR, this raises the intriguing
possibility that these receptors are the molecular target for the antidiabetic
action for this class of compounds.
"The translation of these animal models into the human clinical setting is
promising based on the observation by others that another class of insulin
sensitizer, the thiazolidinediones, decreased hyperglycemia, hyperinsulinemia
and hypertriglyceridemia in animal models of NIDDM and appears to be effective
in recently conducted early stage human clinical trials of type II diabetes."
Preclinical Data From NMU Rat Model of Mammary Carcinoma
Other data presented by Dr. Heyman indicate Targretin(TM) (LGD1069) may be
useful in the treatment or prevention of human breast cancer. In a
preclinical study, Targretin (LGD1069) was examined in a carcinogen-induced
(i.e. NMU) rat mammary carcinoma model system. Targretin (LGD1069) treatment
was compared to treatment with tamoxifen and a control group (15 animals in
each group) to determine the retinoid's ability to reduce tumor incidence and
tumor frequency. Palpation measurement from week five through week 12 of the
study indicated:
* Targretin (LGD1069) decreased incidence of breast tumor formation in
Sprague-Dawley rats at least as well as tamoxifen. Animals treated with
Targretin (LGD1069) experienced a 90% reduction in breast tumor incidence
versus controls. "Incidence" is the percentage of animals which form tumors
after administration of the carcinogen. By comparison, tamoxifen reduced
tumor incidence by up to 85%.
* Targretin (LGD1069) decreased the number of NMU-induced tumors per
animal at least as well as tamoxifen. Control animals had 3.0 tumors per
animal. Targretin (LGD1069) reduced the mean number of tumors per animal by
85%. Tamoxifen reduced the mean number of tumors per animal by 75%.
* Targretin (LGD1069) treatment had no dose limiting toxicities, while
tamoxifen treatment at higher doses resulted in some dose limiting toxicity
including undesirable reduction in mean animal body weight versus control
animals.
Targretin (LGD1069) is a small organic compound discovered by Ligand
scientists which selectively activates a subclass of retinoid receptors called
RXRs which play an important role in several cellular activities. One of
these activities is called programmed cell death or "apoptosis," a natural
process by which the body rids itself of unwanted cells. Targretin (LGD1069)
is being developed by Ligand in both topical and oral formulations. Topical
Targretin (LGD1069) is entering pivotal Phase III clinical trials for the
treatment of cutaneous T-cell lymphoma (CTCL). In addition, Targretin
(LGD1069) oral formulation is entering pivotal Phase II/III trials for the
treatment of CTCL and is in Phase II trials in lung cancer, head and neck
carcinoma, Kaposi's sarcoma, ovarian cancer, prostate cancer and renal cell
cancer.
Ligand Pharmaceuticals Inc., founded in 1987, is a leader in gene
transcription technology, particularly intracellular receptor (IR) technology
and Signal Transducers and Activators of Transcription (STATs), Ligand applies
IR and STATs technology to the discovery and development of small molecule
drugs to enhance therapeutic and safety profiles and to address major unmet
patient needs in cancer, women's health and skin diseases, as well as
osteoporosis, cardiovascular and inflammatory disease.
This statement contains 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 that: (a) human clinical trials will result from the preclinical
studies discussed herein; (b) that the preclinical results described herein
will be observed in human patients; (c) that these or any new products under
development by Ligand or any of its partners will receive approval from the
U.S. Food and Drug Administration or other authorities to market any of these
products; (d) that, if approved, there will be a market for the drugs; or (e)
that preclinical results will be predictive of any final results.
Targretin (LGD1069) is the trade mark of Ligand Pharmaceuticals Inc.
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SOURCE Ligand Pharmaceuticals. Inc.
CONTACT: Susan E. Atkins of Ligand Pharmaceuticals, 619-550-7687 |
