Ruboxistaurin Reduced Vision Loss In Patients With Moderate To Severe Non-Proliferative Diabetic Retinopathy In A New Study

Eli Lilly and Company (NYSE: LLY) today announced results from a three-year phase 3 clinical trial in which ruboxistaurin mesylate (proposed brand name Arxxant(TM), pronounced ark-ZONT) reduced the risk of sustained moderate vision loss by 40 percent when compared to placebo in patients with moderate to severe non-proliferative diabetic retinopathy (DR).(1)

The study findings were recently published online in the in press version of Ophthalmology and will be published in the print version of the December 2006 issue of Ophthalmology.

Diabetic retinopathy (DR) occurs when diabetes damages the small blood vessels in the retina, a part of the eye that is needed for vision. This damage can lead to vision loss and possible blindness. DR affects an estimated 4.1 million Americans age 40 and older, with 899,000 having a vision- threatening form of the disease,(2) and it is the leading cause of blindness among working-age adults.(3) Yet blindness is only a part of the story. Even moderate vision loss can lead to difficulties in reading, driving, employment, and mobility as well as an increased risk of accidental injuries.(4,5,6)

Study Details

Vision loss (measured in the study as sustained moderate vision loss or SMVL) occurred in only 5.5 percent of patients treated with ruboxistaurin compared to 9.1 percent of patients treated with placebo, equaling a 40 percent relative risk reduction (P=0.034) over three years.(1) Vision loss (SMVL) was defined as a three-line loss on a standard eye chart that was sustained for at least 6 months.(1)

This multi-center, 36-month, placebo-controlled, double-masked, phase 3 clinical trial, labeled protein kinase C-diabetic retinopathy study 2 (PKC- DRS2), involved 685 patients randomized at 70 clinical sites to either placebo (n=340) or 32 mg per day of ruboxistaurin (n=340).(1) PKC-DRS2 examined whether ruboxistaurin could reduce the risk of long-term, or sustained moderate vision loss caused by non-proliferative diabetic retinopathy.(1) Patients had moderate to severe nonproliferative diabetic retinopathy at the start of the study.(1) Mean visual acuity was better in the ruboxistaurin- treated patients after 12 months. Baseline-to-endpoint visual improvement of greater than or equal to 15 letters was more frequent (4.9% versus 2.4%) and greater than or equal to 15 letter worsening was less frequent (6.7% versus 9.9%) in ruboxistaurin-treated patients compared with placebo (P=0.005). The beneficial effect of ruboxistaurin was not accompanied by a reduction in the progression of study patients from non-proliferative to proliferative diabetic retinopathy.

Patient discontinuations due to adverse events were not statistically different between treatment groups (n=9, 2.6% placebo; n=16, 4.6% ruboxistaurin).(1) There were 36 patient deaths (n=22, 6.5% placebo; n=14, 4.1% ruboxistaurin), none of which were considered by the investigator or sponsor to be related to study drug. There was no consistent pattern of adverse events to suggest a causal relationship between ruboxistaurin and any spontaneously reported adverse event.

About Diabetic Retinopathy

Diabetic retinopathy is a relatively common microvascular complication in individuals with diabetes that can lead to debilitating vision loss.(7) In the United States, 55 people will go blind every 24 hours as a result of diabetic retinopathy.(8) For persons with type 1 diabetes, the crude prevalence of diabetic retinopathy is about 80 percent.(9)

Non-proliferative diabetic retinopathy (NPDR) occurs when the small blood vessels in the retina are damaged.(6) In the most advanced or proliferative stage of diabetic retinopathy (PDR), new blood vessels grow abnormally from the back of the eye(6) and they may subsequently cause severe vision loss.(6)

Vision loss in patients with DR results predominantly from either the consequences of PDR or diabetic macular edema (DME) that involves the center of the macula (the area of the retina that allows sharp vision). DME occurs when the macula swells with fluid.

About Ruboxistaurin

Ruboxistaurin is an investigational therapy for the treatment of moderate to severe non-proliferative diabetic retinopathy. It works by limiting the overactivation of protein kinase C beta (PKC beta), a naturally occurring enzyme that has been linked to the development of diabetic retinopathy. It is the first of a new class of compounds being investigated for the treatment of moderate to severe non-proliferative diabetic retinopathy.

Lilly submitted a new drug application (NDA) to seek approval from the U.S. Food and Drug Administration (FDA) for ruboxistaurin for the treatment of moderate to severe non-proliferative diabetic retinopathy in February 2006. Lilly received an approvable letter from the FDA in August 2006. The FDA has indicated it will require efficacy data from an additional Phase 3 study before it will consider approving the molecule. Lilly has decided to appeal the FDA’s decision and has recently begun discussions with the agency.

Lilly’s Leadership in Diabetes

Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help health care professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients.

About Lilly

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers — through medicines and information — for some of the world’s most urgent medical needs. Additional information about Lilly is available at http://www.lilly.com/.

This press release contains forward-looking statements about the potential of the investigational compound ruboxistaurin for the treatment of diabetic retinopathy and reflects Lilly’s current beliefs. However, as with any pharmaceutical product under development, there are substantial risks and uncertainties in the process of development and regulatory review. There is no guarantee that the product will receive regulatory approvals, or that the regulatory approval will be for the indication(s) anticipated by the company. In particular, there can be no assurance that the company’s appeal of the FDA’s decision will be successful. There is also no guarantee that the product will prove to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly’s filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

P-LLY

(1) Aiello, L, et al. Effect of Ruboxistaurin (RBX) on Visual Loss in Patients with Diabetic Retinopathy: Ruboxistaurin Treatment of Diabetic Visual Loss.

(2) Kempen, et al: The Prevalence of Diabetic Retinopathy Among Adults in the United States. Arch Ophthalmol, 122:552-563 (2004).

(3) Fong, et al: Retinopathy in Diabetes. Diabetes Care, 27:584-587 (2004)

(4) Wulsin, et al: Psychosocial Correlates of Mild Visual Loss. Psychomatic Medicine, 53:109-117 (1991).

(5) Coyne et al: The impact of diabetic retinopathy: perspectives from patient focus groups. Family Practice, 21:445-451 (2004).

(6) Legood et al: Are We Blind to Injuries in the Visually Impaired? A Review of the Literature. Injury Prevention 8:155-160 (2002).

(7) Ciulla, et al: Diabetic Retinopathy and Diabetic Macular Edema Diabetes Care, 26:2653-2664 (2003).

(8) “Epidemic Concerns Fuel Diabetes Prevention and Treatment Efforts.” Press Release; American Medical Association, October 27, 2005

(9) Roy, et al: The Prevalence of Diabetic Retinopathy Among Adult Type 1 Diabetic Persons in the United States Arch Ophthalmol, 122:546-551 (2004).

Eli Lilly and Company
http://www.lilly.com/

Infants Wheeze Less In Homes With Multiple Dogs

Living in a home with multiple dogs may help reduce an infant’s risk for developing wheezing in the first year of life, according to new research from the University of Cincinnati (UC).

Cincinnati researchers, led by David Bernstein, MD, have found that infants living in homes with high levels of endotoxins (bacterial contaminants) and multiple dogs were more than two times less likely to wheeze than other infants.

They found that wheezing was not associated independently with either dog or cat ownership or high levels of indoor endotoxins; however, high endotoxin exposures in homes that also had multiple dogs resulted in less wheezing.

“Our research presents evidence that pet ownership offers a protective effect against development of lower respiratory symptoms in young children,” adds Bernstein.

The UC-led team’s findings conflict with earlier studies suggesting exposure to high endotoxin levels or pet ownership can protect against an increased risk for future allergic diseases, the UC team reports in the December edition of the Journal of Allergy and Clinical Immunology.

“Exposure to high endotoxin levels in the home may not be an important determinant of aeroallergen sensitization during infancy,” explains Bernstein, professor of immunology and senior author for the study. “We do not yet understand how and why exposure to high levels of bacterial endotoxin and multiple dogs in the home exert a protective effect in these high-risk infants from wheezing early in life.”

Endotoxins are natural compounds secreted from pathogens (disease-causing agents) like bacteria that are commonly found in the intestines and feces. Scientists believe that endotoxins can stimulate our immune systems in many different ways.

“Our bodies are programmed to produce allergic responses early in life,” Bernstein explains, “but there are environmental factors like bacterial endotoxins that may modify the immune system and block development of allergies early in life.”

The UC-led team analyzed the effects of pet ownership (cats and dogs) and endotoxin exposure in 520 infants enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) who were identified as being at greater risk for developing allergies because at least one parent had known allergies.

The CCAAPS, funded by the National Institute of Environmental Health Sciences, is a five-year study examining the effects of environmental particulates on childhood respiratory health and allergy development.

Researchers collected dust samples from the infants’ homes to measure endotoxin levels. They also determined the number of siblings and gathered information about the home, including the presence of mold and second-hand smoke. Environmental and food allergy development was monitored through annual skin prick tests.

Previous studies have addressed the role of pet ownership in childhood allergy development; however, findings have been inconsistent, according to Bernstein. Until now, it was unclear whether animal ownership, endotoxin exposure or a combination of the two resulted in wheezing. Bernstein says further research is needed to determine if these early protective effects have long-term benefits.

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Collaborators in this study include Manuel Villareal, MD, of Cincinnati Children’s Hospital Medical Center and UC colleagues Paloma Campo, MD, Hapinder Kalra, MD, Linda Levin, PhD, Tiina Reponen, PhD, Rolanda Olds, Zana Lummus, PhD, Seung-Hyun Cho, PhD, Gurjit Hershey, MD, PhD, James Lockey, MD, Sherry Stanforth and Grace LeMasters, PhD, principal investigator of the CCAAPS.

Contact: Amanda Harper
University of Cincinnati

Short Term Follow-up Proves To Be Helpful For Lung Cancer Patients

Significant changes in tumor growth can be detected through short interval follow-up CT in patients receiving chemotherapy for non-small cell lung cancer, a recent study found. These growths may have important clinical implications in the management of patients, enabling early discontinuation of potentially toxic chemotherapy drugs.

The study, lead by Dr. John F. Bruzzi of the department of diagnostic imaging at the MD Anderson Cancer Center in Houston, TX was done to determine whether short term follow-up CT in patients with non-small cell lung cancer can detect significant changes in tumor size due to disease progression or response to therapy.

The study, which was performed within a thirty-one day time period, had 41 patients, both male and female, ranging from 26-85 years of age. Short-term restaging scans in each patient comprised at least two serial CT studies performed during this time period. A significant change in tumor size was observed in seven of the patients, four of whom had poorly differentiated tumors. There was a 33% decrease in tumor size in one patient in response to chemotherapy. In five patients, tumors increased extensively in size by 20-48% over a period of 31 days or less. This prompted either a change or discontinuation of chemotherapy in all five patients.

“We found that 17% of patients with non-small-cell lung cancer being treated with chemotherapy had a significant change in tumor size on restaging CT performed within thirty-one days of their baseline CT scan,” said Dr. Bruzzi.

“Twelve percent of these patients had tumor progression, while 3% had tumor shrinkage. This response occurred regardless of initial tumor stage, tumor histology or type of treatment received. This means that an early restaging CT that detects tumor progression can allow the clinician to change or discontinue chemotherapy earlier than might otherwise be done, thereby helping to reduce exposure of the patient to costly and potentially toxic chemotherapy agents that are ineffective; it also gives greater confidence to the clinician in continuing therapy that is producing a good tumor response,” said Dr. Bruzzi.

“We believe now that the value of performing early restaging CT should be assessed in a controlled prospective study of a more homogenous population of patients with lung cancer, which could perhaps also incorporate volumetric measurements of tumor size and assess the relative values of restaging CT and CT-PET scanning,” stated Dr. Bruzzi.

The full results of this study will be presented in May 2006 during the American Roentgen Ray Society Annual Meeting in Vancouver, BC.

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About ARRS
The American Roentgen Ray Society (ARRS) was founded in 1900 and is the oldest radiology society in the United States. Radiologists from all over the world attend the ARRS Annual Meeting to take part in instructional courses, scientific paper presentations, symposiums, new issues forums and scientific and commercial exhibits related to the field of radiology. The ARRS is named after Wilhelm Roentgen, who discovered the x-ray in 1895.

Contact: Necoya Lightsey
American Roentgen Ray Society

Type 2 Diabetes Epidemic In Asia

The proportion of people with type 2 diabetes and obesity has increased throughout Asia, and the rate of increase shows no sign of slowing. Type 2 diabetes has now reached epidemic levels in Asia, according to a Review in this week’s issue.

People in Asia develop diabetes at a younger age and lower weight, suffer longer with chronic diabetes complications, and die sooner than those in developed countries, state Kun Ho Yoon (Department of Internal Medicine, Kangnam St Mary’s Hospital, Seoul, South Korea) and colleagues. The health consequences of this epidemic threaten to overwhelm health-care systems in the region and urgent action is needed.

The behavioural patterns of the young in Asia have changed rapidly. Unlike the gradual transition in nutrient availability that happened in the US and most European countries, this change has happened rapidly in many lower-income countries. Fast foods are readily available and lifestyles have become more sedentary due to computers, TV, academic study, poor urban planning, and cars. In China, the proportion of children aged 7 to 18 years who were obese and overweight increased 28-fold between 1985 and 2000. The onset of type 2 diabetes in younger age-groups is likely to result in major economic burdens for countries in Asia due to premature ill health and death.

India and China have the greatest numbers of people with diabetes in the world, and by 2025 they could each have 20 million affected individuals. In Korea, Indonesia, and Thailand, the prevalence rates of type 2 diabetes have increased three-fold to five-fold during the past 30 years.

“Although the prevalence in Asia is currently similar to that in the US, the rate at which diabetes has increased and the likelihood that it will continue to increase at this rate, provide substantial grounds for concern,” states Professor Yoon. “The cost of inaction is clear and unacceptable”.

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Contact: Joe Santangelo
Lancet

Alimera Sciences Receives FDA Approval To Market Alaway(TM) OTC For Up To 12 Hours Of Eye Itch Relief

Alimera Sciences Inc., an ophthalmic pharmaceutical company founded just three years ago, today announced that the U. S. Food and Drug Administration (FDA) has approved its ophthalmic solution Rx-to-OTC-switch new drug application (NDA) for Alaway(TM) (ketotifen fumarate ophthalmic solution 0.025%). Alaway(TM), a multiple action eye anti-allergic, is Alimera’s first NDA submission and the first to win approval. Indicated for the temporary relief of itchy eyes, Alaway(TM) will be marketed over-the- counter with the prescription strength active ingredient found in a prescription allergy eye drop.

An estimated 40 million people cope with itchy eyes associated with pollen, ragweed, grass, animal hair and dander — particularly during the spring and fall months. Unlike over-the-counter anti-itch eye drop products currently available, just one dose of Alaway(TM) offers eye itch relief within minutes and lasts up to 12 hours. Other over-the-counter products currently available offer no more than four hours of relief and require four doses per day. Alaway(TM), with its unique property of being both an antihistamine and a mast cell stabilizer addresses itchy eyes, the number one complaint among eye allergy sufferers.

“Developing Alaway(TM), submitting the application and achieving FDA approval for a three-year-old company is, indeed, an accomplishment of which Alimera is tremendously proud,” said Dan Myers, president and chief executive officer of Alimera Sciences. “The FDA’s approval of Alaway(TM) marks a milestone in Alimera’s overall strategy to consistently deliver innovative solutions to patient needs.

Alimera initially filed the NDA for Alaway(TM) in February of this year after completing a successful clinical study that showed it to be bioequivalent to Novartis’ Zaditor(R) (ketotifen fumarate ophthalmic solution 0.025%). Alaway(TM), in a 10mL bottle, is expected to be available to consumers in time to provide prescription strength relief for the spring 2007 allergy season.

About Alimera Sciences Inc.

Alimera Sciences Inc., a venture backed company, specializes in the development and commercialization of over-the-counter and prescription ophthalmology pharmaceuticals. Founded by an executive team with extensive development and revenue growth expertise, Alimera Sciences’ products address both the anterior (front) and posterior (back) segments of the eye. In August 2004, Alimera Sciences unveiled Soothe(R), the market’s first multi-dose, emollient-based artificial tear product, and in October 2005 initiated a Phase III clinical trial to study diabetic macular edema (DME) patients treated using Medidur(TM) with fluocinolone acetonide, the company’s pharmacologic treatment for DME.

Alimera Sciences Inc.
http://www.alimerasciences.com

Gender May Impact Lung Function In Patients With Lung Cancer

New research shows that many women recently diagnosed with lung cancer have normal lung function and perform better on lung function tests compared with their male counterparts. A study published in the May issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians (ACCP), shows a significant proportion of women with newly diagnosed lung cancer presented with normal lung function on pulmonary function tests. Furthermore, among patients with lung cancer, significantly more men than women presented with COPD, a well-known independent risk factor for lung cancer that progressively and permanently reduces lung function.

“These findings suggest that the susceptibility patterns among women may be different compared with men,” said Raghu Loganathan, MD, FCCP, Lincoln Medical and Mental Health Center, Bronx, NY. “Using the presence of COPD alone as a criterion to determine a patient’s risk may miss women with lung cancer.”

Dr. Loganathan and colleagues from Memorial Sloan-Kettering Cancer Center in New York used pulmonary function testing to compare the prevalence of COPD in 151 men vs 143 women who were newly diagnosed with lung cancer. Spirometry testing was used to determine pulmonary function. Patients were considered to have COPD when the FEV1/FVC ratio was lower than 70 percent; an FEV1/FVC ratio of greater than 70 was considered normal lung function. At the time of diagnosis, 72.8 percent of men presented with COPD compared with 52.4 percent of women. Among patients who smoked (87 percent), COPD occurred in 74.8 percent in men and 57.3 percent in women. Overall, smoking status and older age were strongly associated with COPD. Both former and current smokers were about 10 times more likely to have COPD compared with nonsmokers.

“The absence of COPD should not lower the risk in a female patient who is otherwise considered to be at increased likelihood for developing lung cancer,” said Dr. Loganathan. “Physicians must consider additional (and well- established) risk factors, such as smoking history and age of the patient, when contemplating lung cancer screening.” The researchers also suggest that gender-based differences in spirometry should be considered in constructing strategies for screening for lung cancer.

Although screening for lung cancer is currently not a standard level of care, persons considered suitable candidates for lung cancer screening include those with heavy smoking history (> 30 pack years), age greater than 50 years, presence of COPD, occupational exposure to asbestos, or history of exposure to radiation. Currently, most screening programs and clinical trials choose patients for lung cancer screening based on smoking history and not on the presence or absence of COPD.

“Understanding the role that gender has in the development of lung cancer may help identify more advanced screening methods and new approaches to preventive care,” said W. Michael Alberts, MD, FCCP, President of the American College of Chest Physicians.

CHEST is a peer-reviewed journal published by the ACCP. It is available online each month at http://www.chestjournal.org . The ACCP represents 16,500 members who provide clinical respiratory, sleep, critical care, and cardiothoracic patient care in the United States and throughout the world. The ACCP’s mission is to promote the prevention and treatment of diseases of the chest through leadership, education, research, and communication. For more information about the ACCP, please visit the ACCP Web site at http://www.chestnet.org .

American College of Chest Physicians
http://www.chestnet.org

Sustained Reduction Of Type 2 Diabetes Achieved With Simple Lifestyle Interventions

Giving people at high risk for type 2 diabetes intensive diet and exercise counselling can result in sustained lifestyle changes and a reduction in diabetes incidence, even after active counselling ceases, according to the extended follow-up of the Finnish Diabetes Prevention Study (FDPS) published in this week’s Lancet.

Around 50% of people with impaired glucose tolerance will develop diabetes during 10 years when no active intervention is applied. In the original FDPS study, overweight, middle-aged people with impaired glucose tolerance were randomly assigned to an intensive lifestyle intervention or control group. The intervention group were given detailed and individualised counselling to achieve lifestyle goals (weight loss, decreased intake of fat and saturated fat, increased fibre intake, and moderately intense physical activity 30 min per day or more). After 4 years of active counselling, the intervention group achieved a 58% reduction in relative risk of type 2 diabetes compared with the control group.

The extended follow-up of the FDPS study assessed the extent to which the originally-achieved lifestyle changes and risk reduction remained after discontinuation of active counselling. Jaana Lindstrцm (National Public Health Institute, Helsinki, Finland) and colleagues found that beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention, with a 36% reduction in relative risk. The overall risk reduction was related to the success in achieving the intervention goals of weight loss, reduced intake of total and saturated fat, and increased physical activity and intake of dietary fibre. The study (with a median follow-up of 3 years after active counselling) shows that a marked difference in the cumulative incidence of diabetes can be sustained after the discontinuation of active counselling.

Jaakko Tuomilehto, the other principal investigator of the Finnish Diabetes Prevention Study states: “From a public health point of view there is an important message: an intensive lifestyle intervention lasting for a limited time can yield long-term benefits in reducing the risk of type 2 diabetes in high-risk individuals. Although a lifestyle intervention alone, even if successful, does not necessarily prevent type 2 diabetes in all individuals, it will still postpone the onset of the disease. Even delaying the onset of diabetes can have a substantial effect on subsequent morbidity, and therefore on the cost-effectiveness of diabetes prevention”.

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See also accompanying Comment.

Contact: Joe Santangelo
Lancet

City Kids With Asthma Lose Out On Preventive Treatment

A new study by specialists at the Johns Hopkins Children’s Center and elsewhere suggests that only one in five inner-city children with chronic asthma gets enough medicine to control dangerous flare-ups of the disease.

The findings, reported in December’s Pediatrics, are disturbing, the researchers say, because preventive therapy failure leads to over-reliance on fast-acting ‘rescue’ drugs after an asthma attack strikes and to more complications and increased risk of death.

The scientists interviewed parents of 180 Baltimore city children 2 to 9 years of age diagnosed with persistent asthma and studied pharmacy records. Overall, only 20 percent of the 180 got the recommended amount of daily controller medication, which is six or more refills in a 12-month period. Sixty percent of children got too little therapy to fully prevent flare-ups and 20 percent either got no medication at all or relied solely on quick-relief rescue drugs, which stop an asthma attack from progressing.

Current guidelines call for any child asthmatic with wheezing, coughing and shortness of breath two or more times a week or night-time symptoms two or more times a month to use inhaled corticosteroids as controller drugs to curb inflammation and prevent acute attacks.

“It’s clear that kids who need preventive drugs aren’t getting them,” says lead author Arlene Butz, Sc.D., R.N., asthma specialist at the Children’s Center. Previous research indicates that inner-city children are at special risk because their living conditions include other asthma triggers, such as exposure to secondhand smoke and mouse and cockroach allergens.

The survey also showed that children cared for by asthma specialists in or out of the hospital were more likely to follow a proper drug regimen than those who were not in these groups.

Butz and colleagues said training primary care pediatricians to check pharmacy records will help them monitor their patients’ adherence to the prescribed drug regimen.

Asthma is the country’s leading pediatric chronic illness, affecting 6.2 million children under the age of 18.

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Other Hopkins researchers in the study: Kim Mudd, M.S.N., of the Children’s Center; and Michele Donithan, M.H.S., of the Johns Hopkins Bloomberg School of Public Health.

Other institutions participating in the study: University of Maryland. The study was funded by the National Institute of Nursing Research.

Contact: Katerina Pesheva
Johns Hopkins Medical Institutions

New Drug Application For Xcytrin(R) For Treatment Of Lung Cancer Patients With Brain Metastases

Pharmacyclics, Inc. (Nasdaq: PCYC) today announced that the company plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) to market Xcytrin(R) (motexafin gadolinium) Injection for the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (i.e., lung cancer that has spread to the brain from another part of the body).

The company also announced that new analyses and additional data from its Phase 3 SMART (Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) trial will be presented at the upcoming Annual Meeting of the American Society of Clinical Oncology (ASCO) in Atlanta. Details on the oral presentation are as follows:

Abstract #7014: “Motexafin gadolinium (MGd) combined with prompt whole brain radiation therapy (RT) prolongs time to neurologic progression in non-small cell lung cancer (NSCLC) patients with brain metastases: Results of a Phase 3 trial,” Minesh P. Mehta, M.D., Dept. of Human Oncology, University of Wisconsin, Madison, Saturday, June 3, 2006, 5:30 – 5:45 p.m. The presentation will be followed by a discussion by Laurie E. Gaspar, M.D., Professor and Chair of Radiation Oncology at the University of Colorado.

The SMART trial was conducted at 94 centers in North America, Europe and Australia and enrolled 554 patients with brain metastases from NSCLC. This randomized, controlled Phase 3 trial compared the safety and efficacy of whole brain radiation therapy (WBRT) alone to WBRT plus Xcytrin. The primary endpoint of the study was time to neurologic progression as determined by a blinded events review committee.

“We plan to file an NDA for Xcytrin primarily based on the data fromhttp://www.pharmacyclics.com our pivotal SMART trial,” said Richard A. Miller, M.D., president and CEO of Pharmacyclics. “New data from the SMART trial, which will be included in the NDA filing, will be presented and discussed at ASCO. We anticipate filing the Xcytrin NDA by the end of 2006.”

About Xcytrin

Pharmacyclics is developing Xcytrin as an anti-cancer agent with a novel mechanism of action that is designed to selectively concentrate in tumors and induce apoptosis (programmed cell death). Xcytrin is a redox-active drug that has been shown to disrupt redox-dependent pathways in cells and inhibit oxidative stress related proteins. Its multifunctional mode of action provides the opportunity to be used in a broad range of cancers. Xcytrin has been granted Fast Track designation by the FDA for use in the treatment of lung cancer brain metastases. This designation is reserved for new drugs that demonstrate the potential to address an unmet medical need and are intended for the treatment of a serious or life-threatening condition.

About Pharmacyclics

Pharmacyclics is a pharmaceutical company developing innovative products to treat cancer, atherosclerosis and other serious diseases. The company is leveraging its small-molecule drug development expertise to build a pipeline in oncology and other diseases based on a wide range of targets, pathways and mechanisms. Its lead product, Xcytrin, has completed Phase 3 clinical testing in lung cancer brain metastases and several Phase 1 and Phase 2 clinical trials are ongoing with Xcytrin, either as a single agent or in combination with chemotherapy and/or radiation in multiple cancer types. Pharmacyclics has other product candidates in earlier-stage development for cancer and inflammatory diseases. More information about the company, its technology, and products can be found at http://www.pharmacyclics.com. Pharmacyclics(R), Xcytrin(R) and the “pentadentate” logo(R) are registered trademarks of Pharmacyclics, Inc.

NOTE: Other than statements of historical fact, the statements made in this press release about enrollment and future plans for our clinical trials, progress of and reports of results from preclinical and clinical studies, including results from our SMART trial, clinical development plans and product development activities are forward-looking statements, as defined in the Private Securities Litigation Reform Act of 1995. The words “potential,” “project,” “believe,” “will,” “continue,” “plan,” “expect,” “intend,” “anticipate,” variations of such words, and similar expressions also identify forward-looking statements, but their absence does not mean that the statement is not forward-looking. The forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those in the forward-looking statements. Factors that could affect actual results include risks associated with the initiation, timing, design, enrollment and cost of clinical trials; unexpected delays in and unanticipated increases in costs related to our preclinical studies and clinical trials; the fact that data from preclinical studies and Phase 1 or Phase 2 clinical trials may not necessarily be indicative of future clinical trial results; our ability to obtain future financing and fund the product development of our pipeline; the outcome of our discussions with the FDA; our ability to prepare and submit an NDA on a timely basis or at all; the possibility that the FDA refuses to accept any NDA we submit; the possibility that additional data or studies may be required before the NDA is accepted for filing or approved by the FDA; our ability to establish successful partnerships and collaborations with third parties; the regulatory approval process in the United States and other countries; and future capital requirements. For further information about these risks and other factors that may affect the actual results achieved by Pharmacyclics, please see the company’s reports as filed with the U.S. Securities and Exchange Commission from time to time, including but not limited to its quarterly report on Form 10-Q for the period ended December 31, 2005. Forward-looking statements contained in this announcement are made as of this date, and we undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Pharmacyclics, Inc.
http://www.pharmacyclics.com/

High Blood Glucose Responsible For Over 3 Million Deaths Worldwide

In addition to almost one million diabetes deaths, high blood glucose is responsible for 2.2 million cardiovascular* deaths worldwide, according to an Article in this week’s issue of The Lancet. The findings mean that one in five deaths from ischaemic heart disease** and one in eight from stroke worldwide are attributable to higher-than-optimum blood glucose.

A person’s risk of death from heart disease or stroke increases continuously with their blood glucose level, from concentrations well below conventional thresholds used to define diabetes. Deaths that are directly linked to diabetes therefore underestimate the total burden of the condition.

In the latest study Goodarz Danaei, Majid Ezzati (Harvard School of Public Health, Boston, MA, USA) and colleagues quantified the effects of higher-than-optimum concentrations of blood glucose on mortality from ischaemic heart disease and stroke worldwide. The investigators gathered data on blood glucose from 52 countries in different world regions. They found that in 2001, 960 000 deaths were directly assigned to diabetes in the world. In addition to these deaths, worldwide 1.5 million deaths from ischaemic heart disease and 700 000 deaths from stroke were caused by blood glucose levels that were high but lower than the traditional definition of diabetes. These results show that total mortality from higher-than-optimum blood glucose is 3•16 million; substantially higher than the 960 000 deaths coded to diabetes. This figure is comparable to deaths from smoking (4•8 million), high cholesterol (3•9 million), and overweight and obesity (2•4 million).

The authors conclude: “Higher-than-optimum blood glucose is a leading cause of cardiovascular mortality in most world regions. Cardiovascular risk and diabetes management and control programs need to be more closely integrated rather than being in different spheres.” (Quote by e-mail; not in published paper)

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See also accompanying Comment.

*Cardiovascular disease – class of diseases that involve the heart and/or blood vessels

**Ischaemic heart disease – characterised by reduced blood supply to the heart muscle

Contact: Joe Santangelo
Lancet