Here's the press release on the Nature study:
'Nature' Study Finds Ligand and ALRT Compounds Increase Efficiency of Insulin in
Body; Could Ultimately Delay Diabetes
Targretin(TM) Already in Phase II Diabetes Trials
SAN DIEGO, March 26 /PRNewswire/ -- A new class of retinoids, acting as
insulin sensitizers, could eventually help more than 15 million Americans with
diabetes halt progression of the potentially fatal disease, a study in today's
issue of the journal "Nature" concludes.
Researchers at Ligand Pharmaceuticals (Nasdaq: LGND) found that the RXR
selective retinoids, Targretin(TM) (LGD 1069) and ALRT268, enabled diabetic
mice to use insulin more efficiently resulting in significantly reduced
glucose, insulin and triglyceride levels, important measures of the onset of
and abnormalities associated with diabetes.
Using two well-studied mouse models of non-insulin dependent diabetes
mellitus (NIDDM or type II diabetes), the investigators compared the anti-
diabetic effects of Targretin and ALRT268 to treatment with a second
generation member of a new class of recently approved anti-diabetic drugs
called thiazolidinediones (TZDs), and with a control group.
"We found that Targretin and ALRT268 reduced glucose levels by
approximately 40 percent and that ALRT268 reduced insulin levels by 70
percent," said Dr. Richard A. Heyman, the study's author and Senior Director
of Retinoid Research at Ligand. "In addition, both compounds were capable of
reducing triglycerides, an important risk factor in cardiovascular disease.
In combination with a potent TZD used in this study, RXR agonists reduced the
glucose and triglyceride levels even further."
Ligand is developing Targretin in both topical and oral formulations on
its own behalf, and Ligand and Allergan are developing the second generation,
RXR-selective, preclinical compound ALRT268 on behalf of Allergan Ligand
Retinoid Therapeutics, Inc. (ALRT).
Targretin Research Now in Phase II Trials
The positive results reported today in 'Nature' highlight the opportunity
for further expansion of Ligand's retinoid clinical trial program. Last week,
the company announced the commencement of clinical human Phase II trials with
Targretin for treatment of type II diabetes in Europe. More extensive trials
are planned in the United States this year.
"A key question in pharmaceutical research is whether the preclinical
results in animal studies, will translate into safety and efficacy in humans,"
according to Andres Negro-Vilar, Senior Vice President, Research and Chief
Scientific Officer of Ligand Pharmaceuticals, Inc. "Targretin is particularly
exciting because, even before the diabetes trial, Ligand has had human
clinical trials under way for a wide range of cancers for nearly three years,
and results from these trials have already provided evidence that the drug has
an acceptable safety profile in cancer patients at high doses," said Dr.
Negro-Vilar.
"We are now able to evaluate the safety and efficacy of the drug in this
diabetic patient population. We have cautious optimism about the translation
of the animal efficacy data because TZDs, which have also shown promise in
these animal models, have been translated into human type II diabetes clinical
trials, and now a marketed drug," according to Dr. Heyman.
Insulin Resistance; A Growing Concern
The risk of developing insulin resistance, a deficiency in the body's
ability to use insulin efficiently, increases with age and with obesity.
Insulin-resistant individuals need more insulin to meet their basic metabolic
needs. People with type II diabetes are often severely insulin-resistant and
consequently need to produce so much insulin that their insulin-producing
cells cannot keep up with their bodies' demands and ultimately fail.
"These animal data show that drugs like Targretin have the potential to
delay disease progression in insulin resistant patients with type II
diabetes," Dr. Heyman said.
Diabetes is the fourth leading cause of death by disease in the United
States with an estimated annual cost to the economy of $92 billion, according
to the American Diabetes Association. Type II diabetes is the most common
form of the disease, affecting more than 15 million Americans.
RXR Mechanism of Action
Targretin, a small organic compound discovered by Ligand scientists,
selectively activates a subclass of retinoid receptors called retinoid X
receptors (RXRs) that play an important role in several cellular activities.
ALRT268 is a second generation RXR selective compound owned by Allergan Ligand
Retinoid Therapeutics, Inc. Scientists have known for several years that
retinoids that bind to the RXR receptors deliver their therapeutic effects by
partnering with other intracellular receptors in an activated complex called a
heterodimer. The RXR can partner with several other intracellular receptors
with different physiologic effects. One of these partners is peroxisome
proliferator activated receptor (PPAR) gamma, a target of the antidiabetic
class of drugs, the TZDs.
When the RXR receptor is linked to PPAR gamma receptor which is a target
for antidiabetic therapies; the RXR ligand activates the pair and can have an
antidiabetic effect. The recently approved TZD is known to exert at least
part of its antidiabetic effects through PPAR receptors.
In addition to glucose metabolism, RXRs also play an important role in
other cellular activities such as programmed cell death or "apoptosis," a
natural process by which the body eliminates unwanted cells. Topical
Targretin is in pivotal Phase III clinical trials for the treatment of
cutaneous T-cell lymphoma (CTCL). In addition, Oral Targretin is in pivotal
Phase II/III trials for the treatment of CTCL. It is also in Phase II/III
trials in lung cancer, and in Phase IIb trials for head and neck carcinoma,
Kaposi's sarcoma, ovarian cancer, prostate cancer and renal cell cancer.
Targretin is a compound discovered and developed by Ligand. ALRT268 is a
compound of Allergan Ligand Retinoid Therapeutics Inc. (Nasdaq: ALRIZ), a
research and development company formed by Ligand and Allergan, Inc.
(NYSE: AGN) to develop retinoid pharmaceutical products. Ligand and Allergan
share specific buyback rights to all compounds and assets of ALRT. Ligand
owns 100% worldwide rights to Targretin in all indications.
Ligand Pharmaceuticals Inc., founded in 1987, is a leader in gene
transcription technology, particularly intracellular receptor (IR) technology,
including retinoids like Targretin, 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
and men's health and skin diseases, as well as osteoporosis, metabolic,
cardiovascular and inflammatory disease.
Allergan Ligand Retinoid Therapeutics, Inc. was formed in 1994 to discover
and develop drugs base on retinoids. Retinoids have a broad range of
biological actions, and evidence suggests they may be useful in the treatment
of a variety of cancers including leukemias and certain metabolic, skin and
eye 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 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 is the trademark of Ligand Pharmaceuticals Inc.
If you would prefer to receive Ligand press releases via email, please
inform Ligand at investors@ligand.com and request to be placed on the priority
email list.
SOURCE Ligand Pharmaceuticals
CONTACT: Susan Atkins of Ligand Pharmaceuticals, 619-550-7687; or
John Bluth of Fleishman-Hillard, media, 212-265-9150 |
