Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease, announced that Dr. Philip Brown, senior vice president of clinical development at Lexicon, delivered an oral presentation at the annual meeting of the European Neuroendocrine Tumor Society (ENETS). The presentation summarized Phase 1 clinical trial results for LX1032, Lexicon’s orally-delivered small molecule drug candidate for managing gastrointestinal symptoms associated with carcinoid syndrome. The clinical studies, conducted to date in healthy volunteers, indicated that the drug candidate reduced serotonin levels in humans as predicted by Lexicon’s mouse models and preclinical research. Lexicon is planning to initiate a Phase 2 clinical trial of LX1032 in patients with carcinoid syndrome in the first quarter of 2009.

A copy of the presentation will be available on the company’s corporate website at http://www.lexpharma.com.

About ENETS

The ENETS conference is a medical conference focused on diagnosis and treatment of neuroendocrine tumors including carcinoid. The meeting brings together leading neuroendocrine tumor experts from around the world in such fields as oncology, pathology, radiology, nuclear medicine, endocrinology, surgery and gastroenterology. The 2009 ENETS conference runs from March 5-7 in Granada, Spain.

About Carcinoid Syndrome and LX1032

Carcinoid syndrome is a chronic condition that is the result of metastatic neuroendocrine tumors that usually originate from the gastrointestinal tract. These tumors secrete large amounts of serotonin, which can cause a variety of symptoms including severe diarrhea and abdominal discomfort. LX1032 acts to reduce serotonin production by inhibiting tryptophan hydroxylase (TPH), a key enzyme in the synthesis of serotonin.

LX1032 is being developed in a product development collaboration with Symphony Capital Partners, L.P. and its co-investors.

About Lexicon

Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome, all of which were discovered by the company’s research team. The company has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs. For additional information about Lexicon and its programs, please visit http://www.lexpharma.com.

Safe Harbor Statement

This press release contains “forward-looking statements,” including statements relating to Lexicon’s clinical development of LX1032 and the potential therapeutic and commercial potential of LX1032. This press release also contains forward-looking statements relating to Lexicon’s growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon’s ability to successfully conduct clinical development of LX1032 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Factors Affecting Forward-Looking Statements” and “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2007, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

Goserelin, a lutenizing hormone-releasing hormone agonist, reduces the long-term risk of disease recurrence and deaths in premenopausal women with early breast cancer who did not take tamoxifen, according to trial data reported in the February 24 online issue of the Journal of the National Cancer Institute.

Systematic reviews have shown that lutenizing hormone-releasing hormone agonists, including goserelin, reduce the risk of disease recurrence and death due to breast cancer in premenopausal women. However the long-term impact of goserelin was not known, particularly in comparison to women who did or did not take tamoxifen.

Women with breast cancer were randomly assigned to take goserelin (Zoladex), tamoxifen, both agents, or neither drug for two years in the Zoladex in Premenopausal Patients study. In this analysis, which included 2,706 women, Allan Hackshaw, of the Cancer Research UK Trials Centre at University College London, and colleagues examined the long-term impact of the agents on various outcomes, including the risk of the cancer returning and the risk of dying from breast cancer or any cause.

The effect of two years of goserelin treatment was comparable to that conferred by two years of tamoxifen. Among patients who took goserelin alone, there were 13.9 fewer events per 100 women 15 years after starting treatment, compared with those who did not take either drug. Among women who took both drugs, the benefit of adding goserelin to tamoxifen was smaller (2.8 fewer events per 100 patients) and did not reach statistical significance.

The number of breast cancer deaths was lower by 8.5 per 100 women in those who took goserelin alone, compared to those who took neither drug. The difference was statistically significant. Among those who added goserelin to tamoxifen, there was an additional reduction of 2.6 deaths per 100 women. But again, the additional reduction was not statistically significant.

“In summary, long-term follow-up of our large trial showed that goserelin had a demonstrable effect on survival and recurrence 15 years after starting treatment and is as effective as tamoxifen when each are given for 2 years,” the authors write. “It may be that women who are unlikely to complete 5 years of tamoxifen tablets may prefer 2 years of goserelin injections.”

Citation: Hackshaw A et al. Moderate Long-term effectiveness of adjuvant goserelin in pre-menopausal women with early breast cancer. Journal of the National Cancer Institute 2009;101:341-349

The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Visit the Journal online at http://jnci.oxfordjournals.org/.

Children treated for hypothyroidism aren’t likely to drop pounds with treatment for the condition says a new study in the Journal of Pediatrics. The study is the first to examine the link between hypothyroidism treatment and weight loss in pediatric patients.

“Parents of overweight children often desire a ‘quick fix’ for the problem and request thyroid tests, but, unfortunately, screening for hypothyroidism is not the answer,” said the study’s lead author, Dr. Jefferson P. Lomenick, an assistant professor at the University of Kentucky College of Medicine Department of Pediatrics’ Division of Pediatric Endocrinology. “Most experts agree thyroid function tests are generally unnecessary in an overweight child if he/she has normal linear growth and no other symptoms of hypothyroidism. The results of our study support this.”

The study followed 68 children with acquired hypothyroidism treated in the pediatric endocrinology clinic at Kentucky Children’s Hospital from 1995 to 2006. Most of the subjects had severe cases of hypothyroidism. Researchers found treatment with levo-thyroxine, which normalized the children’s thyroid levels, did not lower weight or BMI from baseline to any time point measured, either short-term or long-term.

“These findings were true for the group as a whole, as well as those children who were overweight,” Lomenick said. “In fact, the entire group of 68 subjects actually gained 2.4 pounds by the first follow up visit despite their treatment. We did find that about a third of the children experienced weight loss by the second visit. However, these subjects had extremely severe cases of hypothyroidism, far worse than the children who did not lose weight, and they didn’t lose that much, only about five pounds.”

Lomenick said he is not surprised by these findings. “Although this is the first study in children to address this issue, there have been a few reports in adults which show similar results.”

Although hypothyroidism is commonly believed to cause weight gain, Lomenick said the disease has been given a bad reputation.

“Long-standing hypothyroidism causes accumulation of a proteinaceous fluid in the subcutaneous tissues called myxedema,” said Lomenick. “The amount of adipose, or fatty tissue, is not really altered with hypothyroidism. Replacement of thyroid hormone causes this fluid, which only amounts to a few pounds, to dissipate over a few weeks. Most cases of hypothyroidism are actually discovered long before myxedema even develops, which is why the majority of people experience little, if any, weight loss after treatment. The effect of hypothyroidism on weight has been vastly blown out of proportion to reality.”

The study, “Effect of Levo-Thyroxine Treatment on Weight and Body Mass Index in Children with Acquired Hypothyroidism,” was co-authored by Dr. W. Jackson Smith, associate professor of pediatrics and chief of pediatric endocrinology at UK, and Maysa El-Sayyid, a medical student at UK.

University of Kentucky
102A Mathews Bldg.
Lexington, KY 40506-0047
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http://www.uky.edu

Unless Congress acts, on January 1, 2008, the Medicare physician payment schedule will be cut by 10% under the current Medicare formula used to determine annual payment updates. Physician payments have been “frozen” for the past two years. This is devastating news to America’s senior citizens. The American Medical Association (AMA) estimates that the payment formula has kept 2007 physician payment rates the same as they were in 2001, while practice costs have continued to increase annually. According to the AMA, 60 percent of physicians say this cut will force them to reduce or eliminate the number of Medicare patients they treat. That’s why the American Association of Clinical Endocrinologists (AACE) is calling for Congress to take immediate action to stop these cuts from taking effect.

The cuts resulting from the payment formula are especially devastating to endocrinologists’ patients who have chronic disease, such as diabetes and thyroid disorders. These conditions, when left untreated, often result in costly and life threatening complications and hospitalizations.

“The impending reductions in the physician payment schedule will make it impossible for endocrinologists to provide patients with serious endocrine disorders such as diabetes with the level of care they need and deserve,” said Richard Hellman, MD, FACP, FACE, President of AACE. “The decision to tie physician reimbursements arbitrarily to an arcane and flawed formula based on the Gross Domestic Product is crippling our healthcare system.”

Ironically, AACE has been a leader in the government’s efforts to improve quality and safety measures under the Medicare program. Dr. Hellman also serves on the board of the AMA Physician Consortium for Performance Improvement. With that group, AACE continues to be involved in the development of quality measures, including those related to diabetes, hypertension, and osteoporosis. CMS is using some of these measures in its Medicare Physician Quality Reporting Initiative (PQRI).

“What we’re facing is a tug-of-war,” said Hellman. “On one end of the rope, we are working closely with CMS to develop systems to ensure the highest quality care for all Americans. On the other end, we are being told we have to take a 10 percent cut in reimbursements, which will lead to the breakdown of the healthcare infrastructure. In the middle, the patients are feeling the strain.”

AACE has joined with the AMA in urging Congress to act now by blocking the payment cuts and providing positive updates for the next two years while a permanent solution to this problem is developed. AACE encourages patients and their doctors to call their Congressional Representatives and Senators asking them to stop the cuts to the physician payment schedule on January 1, 2008, and to repeal the flawed Medicare payment formula.

About AACE

AACE is a professional medical organization with nearly 6,000 members in the United States and 85 other countries. Founded in 1991, AACE is dedicated to the optimal care of patients with endocrine problems. AACE Clinical Endocrinologists advanced, specialized training enable them to be experts in the care of endocrine disease, such as diabetes, thyroid disorders, growth hormone deficiency, osteoporosis, cholesterol disorders, hypertension and obesity.

Not all unwanted hair growth is simply cosmetic. It can be symptomatic of serious underlying medical conditions which can impact health, well-being and even the reproductive health of many women.

Sharon Ortiz, President of The American Electrology Association, Inc. (AEA), the largest representative organization of professional electrologists in the United States, states “Women should be aware that unusual unwanted hair growth patterns or volume can be cause for some medical concern. Whether the condition is polycystic ovarian syndrome (PCOS), adrenal hyperplasia, thyroid dysfunction, or other endocrine disturbances, hair growth is often the symptom a woman will address first.”

The Cedars-Sinai Medical Center (southern CA) News, Feb. 4, 2004, cites a long-term study by the Center for Androgen Related Disorders in which Ricardo Azziz, MD, MPH, MBA, Director, notes that although androgen excess is recognized as the most common endocrine disorder among women in their reproductive years, its causes are not always easy to determine. In a large scale analysis of women with androgen excess, more than 80% suffered from hirsutism (excess hair growth), menstrual dysfunction and acne. Because most androgen excess disorders begin around the onset of puberty, most women appear to suffer without intervention. It was noted by researchers that “up to 80% of patients are not recognized, evaluated or treated in a timely fashion.”

Electrologists note that women with an excess of androgen grow hair in a much different manner from most other women they see. Their facial and body hair growth could rival that of a man’s. This masculine hair growth pattern on both the face and body is very worrisome to these clients and much of their energy is spent trying to look as though the hair growth doesn’t exist.

Since professional electrologists are trained to recognize the signs of androgen excess, when a client comes in to address the cosmetic symptoms, they are likely to be referred to their primary care physician or an endocrinologist for evaluation. While electrology treatments go forward, the cause of the unwanted hair growth can be mitigated through appropriate medical treatment. The impact of having been directed to medical care can greatly benefit many other areas of their lives.

Dr. Carmela Abraham, a professor of biochemistry and medicine at Boston University School of Medicine (BUSM), reports this week in the Proceedings of the National Academy of Sciences new findings on Klotho, an anti-aging gene that is associated with life span extension in rodents and humans. Dr. Abraham’s interest in Klotho stems from her studies comparing the expression of genes in young and old brains.

Dr. Abraham and her colleagues observed that the levels of Klotho in the brain showed a striking decrease with aging. The association between Klotho and aging prompted Abraham’s group to investigate the regulation of Klotho further. These studies lead to the observation that secretion of Klotho is regulated by insulin.

The Klotho protein sits in the membrane of certain cells but is also found circulating in serum and cerebrospinal fluid, which indicates that it is secreted. The fact that Klotho is secreted suggested that enzymes that act like scissors must be involved in the liberation of Klotho from the cell membrane.

Dr. Ci-Di Chen, an assistant professor working in Dr. Abraham’s group, then sought to identify the enzymes responsible for Klotho release and also investigated other factors that may affect the release of active Klotho.

To their surprise, they found that insulin, a hormone usually associated with diabetes, increases significantly the levels of secreted Klotho. The reason this finding is important is because excess insulin has been previously implicated in a biochemical pathway that is associated with a decreased life span and elevated oxidative stress.

In addition, this observation provides a potentially pivotal link between Klotho and sugar metabolism, and raises an intriguing relationship between Klotho and type II diabetes, commonly known as late onset diabetes. The authors are proposing a novel mechanism of action for Klotho whereby insulin increases Klotho secretion, i.e., activity, and in turn, the secreted Klotho inhibits insulin’s actions in the cell, which are known to be detrimental when insulin is in excess.

Sonia Podvin, Earl Gillespie and Dr. Susan Leeman, all from Boston University School of Medicine, also participated in the study.

Following these findings, the Abraham laboratory is now studying various ways to increase the level of Klotho to those levels found in young individuals. “The findings reported here may lead to new research designed to regulate the aging process, in other words, compounds that would increase Klotho could become the next “fountain of youth,” said Abraham.

Researchers here have shown that in cell cultures, the stress hormone norepinephrine appears to promote the biochemical signals that stimulate certain tumor cells to grow and spread.

The finding, if verified, may suggest a way of slowing the progression and spread of some cancers enough so that conventional chemotherapeutic treatments would have a better chance to work.

The study also showed that stress hormones may play a completely different role in cancer development than researchers had once thought.

The results appear in the current issue of the journal Brain, Behavior and Immunity.

“We would not be surprised if we see similar effects of norepinephrine on tumor progression in several different forms of cancer,” explained Eric Yang, first author of the paper and a research scientist with the Institute for Behavioral Medicine Research (IBMR) at Ohio State University.

Yang and colleague Ron Glaser, a professor of molecular virology, immunology and medical genetics, last year showed that the stress hormone norepinephrine was able to increase the production of proteins in cultures of nasopharyngeal carcinoma tumor cells that can foster the aggressive spread of the disease, a process known as metastasis. Glaser is director of the IBMR and a member of the Comprehensive Cancer Center at Ohio State.

In this latest study, the researchers looked at a different type of cancer multiple myeloma. One of several types of cancers of the blood, multiple myeloma strikes nearly 20,000 Americans each year, killing at least half that many annually. Patients diagnosed with this disease normally survive only three to four years with conventional treatments.

Yang and Glaser focused on three multiple myeloma tumor cell lines, each representing a different stage in the life of the disease, for their experiments. While all three tumor cell lines reacted to the presence of norepinephrine, only one, a cell line known as FLAM-76, responded strongly to the hormone.

The norepinephrine binds to receptors on the surface of the cells, sending a signal to the nucleus to produce a compound known as VEGF — vascular endothelial growth factor that is key to the formation of new blood vessels, which the tumor must have to grow.

The FLAM-76 cell line was prepared from multiple myeloma tumor cells taken from a patient whose disease had not yet progressed too far from its original site in the bone marrow where blood cells are formed.

“It turns out that FLAM-76 tumor cells more closely represent the earlier stages of the disease when blood vessel formation, a process called angiogenesis, is needed for disease progression,” Yang said.

“The fact that this one cell line, of the three multiple myeloma cell lines studied, closely represents the early stages of the tumor, and that this is where we see the biggest effect, is what makes this work more clinically relevant,” Glaser said.

The researchers believe that blocking these receptors would slow the process of the growth of more blood vessel to the tumor, delaying disease progression and perhaps allowing treatments to be more effective. Widely used “beta-blocker” drugs now prescribed for high blood pressure work by blocking these same particular cell surface receptors, Yang said.

“This approach wouldn’t kill the tumor cells but it would diminish the blood supply to the tumor cells and slow them down, and that could translate into a longer and better quality of life for the patient,” Glaser said.

The researchers and their colleagues are now working with other forms of cancer to test the effects of stress hormones like norepinephrine on their growth.

Glaser added that these kinds of results may change the way scientists are looking at a link between stress and the development and spread of cancer. In the past, he said, the focus was on how stress hormones weakened the immune system, allowing certain tumors to evade the body’s defenses.

“Now we have these stress hormones, not only affecting the immune response, but also acting directly on the tumor cells and inducing changes in the molecules made by those same tumor cells,” Glaser said.

“This has important implications for the spread of the tumor and metastasis.”

Elise Donovan, a researcher with the IBMR, and Don Benson, a researcher with Ohio State’s Comprehensive Cancer Center, also worked on the project. The research was funded in part by the National Cancer Institute.

In the current issue of Psychotherapy and Psychosomatics, an endocrinologist of the University of Padova (N. Sonino) and a psychologist of the University of Bologna (G. fava) introduce the concept of rehabilitation in endocrinology and the need of a new type of medical service. Long standing endocrine disorders may imply a degree of irreversibility of the pathological process and induce highly individualized affective responses. The psychosocial impairment that is associated with incomplete remission from endocrine illness suggests the need for an innovative approach to treatment, introducing in clinical endocrinology the concept of rehabilitation, which in other fields of medicine is already established. This new proposal stems from a number of unresolved issues related to the high prevalence of psychosocial impairment in patients adequately treated for various endocrine conditions.

Indeed, rehabilitation in endocrinology may be indicated in the following cases: (a) delayed recovery after appropriate treatment; (b) discrepancy between endocrine status and current functioning; (c) presence of a decline in physical and social functioning; (d) persistence of important comorbidity, with special reference to psychiatric disturbances; (e) assessment of abnormal illness behavior; (f) problems with lifestyle and risk behavior, and (g) potential role of stress in endocrine disturbances. The endocrine rehabilitation team should ideally include a trained clinical endocrinologist, a physical therapist and a psychologist, with opportunities for other specialist consultations. The goal of such service would be to ensure education, support and specific interventions, helping the patient and his/her family to achieve optimal coping with the difficulties of the recovery process. Due to its comprehensive psychosomatic characterization, this new approach would likely increase the chances of obtaining full recovery in a significant proportion of patients and has the potential of being cost effective.