ON TARGET

ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.

1 April 2007

I. WHAT'S NEW?
Regulatory Affairs at Target Health
II. QUIZ - (Fill In The Blanks)
Cognitive Neuroscience
III. HISTORY OF MEDICINE
Criminal Intent?
IV. EPIDEMIOLOGY
Aspirin is Still the Drug of Choice
V. OPHTHALMOLOGY
Inflammatory Biomarkers and Risk of Age-Related Macular Degeneration
VI. CADIOLOGY
Hypertension, Other Risk Factors and Stroke
VII. REGULATORY AFFAIRS
New Biologic Approved For Purpura Fulminans
VIII. TARGET HEALTH

I. WHAT'S NEW

Regulatory Affairs at Target Health

Target Health is pleased to announce that we now represent 20 companies at FDA from all over the world and the US. Countries include England, France, Germany, Israel, Korea, Switzerland and Turkey. We recently prepared and submitted a PMA including an eCopy, and are preparing an eCTD, to be submitted shortly. A special protocol assessment went in this week and last month. We were at FDA 3 times, including a pre-NDA meeting. We have been responsible for 7 orphan drug request approved submissions and multiple IND/IDE in very diverse indications including, but not limited to: Cardiology (IDE; PMA), Cellular Products (IND, CBER), Dermatology (IND; NDA), Gastroenterology (IND), HIV/AIDS (IND), Men's Health (IND), Metabolism (IND), Oncology (IND), Ophthalmology (IND, NDA), Oral Care (PMA) and Women's Health (IDE; IND; 3 NDA's). Glen Park, PharmD, who has been key to growing this department, runs our Clinical and Regulatory operation with Mary Shatzoff, Fredy Varela and Vanessa Hays. Collaborating with Dr. Park is Dr. Jules T. Mitchel, President of Target Health.

This year, we expect 3 products to be sumitted to FDA for marketing clearance (1 NDA, 1 BLA and 1 PMA, submitted) for which we did data management. For the NDA and PMA we also did monitoring, statistics, medical writing and reguatory affairs.

For more information, please contact Dr. Jules T. Mitchel. Visit our Blog and Website.

II. QUIZ (Fill In The Blanks)

Cognitive Neuroscience

In a larger sense, social cognition is an extreme example of a broader issue in biology of mind, and that is social interaction in general. Even here we are beginning to make some rather remarkable progress. Cori Bargmann, a geneticist at the Rockefeller University, has studied two variants of a 1) ___ called C elegans, that differ in their feeding pattern. One variant is 2) ___ and seeks its food alone; the other is social and forages in groups. The only difference between the two is one 3) ___ acid in an otherwise shared receptor protein. If you move the 4) ___ from a social worm to a solitary worm, it makes the solitary worm social. This is one of several examples in which changing a single gene 5) ___the social behavior of an animal. Source: In Search of memory: The Emergence of a New Science of Mind by Eric R. Kandel

ANSWERS: 1) worm; 2) solitary; 3) amino; 4) receptor; 5) alters

III. HISTORY OF MEDICINE

Criminal Intent?

Kenneth Page Oakley [1911–1981] was an English physical anthropologist, geologist, and paleontologist best known for his work in the relative dating of fossils by fluorine content. Oakley won renown in 1953 when he played a decisive role in the exposure of the Piltdown Man hoax. Piltdown Man was the supposed remains of a skull found in a ditch in Sussex, England. For decades, it was said to represent the "missing link" in human evolution. Oakley developed a method ( based on a French mineralogist's theory that bones would gradually absorb fluorine from surrounding soil) to measure the fluorine levels in bones. With this and other tests he proved the true age of the bones to be a modern human braincase and an orangutan jawbone. The bone, unchallenged as the missing link between man and ape since its discovery in 1912 had to be cast aside. This guaranteed Kenneth Oakley his place in anthropological history. Oakley had attended a conference on human origins where he met the anthropologist Joseph Weiner. The two men shared a skepticism about the age of the Piltdown Man remains. Oakley and Weiner decided to run a series of chemical tests to determine a more precise dating of the skull, teeth and jaw fragments. Results showed that the artifacts were not 500,000 years old, but considerably less than 50,000 years old. It was then discovered that many of the artifacts were significantly altered to make them appear older. The teeth were ground down to make them look worn and the bones were stained with paint to make them look ancient. In 1959, radiocarbon tests revealed that the actual age of the human cranium was approximately 600 years old and the jaw, which was discovered to be that of an orangutan, was approximately 500 years old. Not only were the specimens altered to make them appear older but also there was evidence that many of the objects found in Sussex, had been planted at the site. According to Tom Turin's A Mostly Complete Piltdown Man Bibliography, 15 people were implicated in the hoax between 1955 and 1992. In the end, the perpetrators of the fraud of the century, were never determined. Edited by Alex Hays

IV. EPIDEMIOLOGY

Aspirin is Still the Drug of Choice

The influence of long-term use of aspirin on total mortality in women remains uncertain. As a result, a prospective, nested, case-control study of 79 439 women enrolled in the Nurses' Health Study who had no history of cardiovascular disease or cancer study was performed (Archives of Internal Medicine (2007;167:562-572), to evaluate the role of aspirin on mortality. Study participants provided data on medication use biennially since 1980. The relative risk (RR) of death was assessed according to aspirin use before diagnosis of incident cardiovascular disease or cancer and during the corresponding period for each control subject. Results showed that during the 24 years of the study, 9,477 deaths from all causes were documented. In women who reported current aspirin use, the multivariate RR of death from all causes was 0.75 compared with women who never used aspirin regularly. The risk reduction was more apparent for death from cardiovascular disease (RR, 0.62) than for death from cancer (RR, 0.88). Use of aspirin for 1 to 5 years was associated with significant reductions in cardiovascular mortality (RR, 0.75). In contrast, a significant reduction in risk of cancer deaths was not observed until after 10 years of aspirin use (P = .005). The benefit associated with aspirin was confined to low and moderate doses and was significantly greater in older participants (P<.001) and those with more cardiac risk factors (P = .02). It was concluded that in women, low to moderate doses of aspirin are associated with significantly lower risk of all-cause mortality, particularly in older women and those with cardiac risk factors. A significant benefit is evident within 5 years for cardiovascular disease, whereas a modest benefit for cancer is not apparent until after 10 years of use.

V. OPHTHALMOLOGY

Inflammatory Biomarkers and Risk of Age-Related Macular Degeneration

According to an article published in the Archives of Ophthalmology (2007;125:300-305), a study was performed to investigate whether high-sensitivity C-reactive protein (hsCRP) and other biomarkers of inflammation predict age-related macular degeneration (AMD). The study measured hsCRP, soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen levels in baseline plasma samples from 27,687 participants in the Women's Health Study. The mean age was 54.6 years and all participants were initially free of AMD. During the followup period, it was prospectively determined that there were 150 cases of AMD with vision loss of 20/30 or worse in the affected eye by self-report, which was confirmed with review of medical records during 275,852 person-years of follow-up (mean = 10 years). Results showed that after adjustment for multiple risk factors, the hazard ratio (HR) of AMD, contrasting the highest vs lowest quintile of hsCRP, was 3.09 (P = .02). In similar models, the HR for sICAM-1 was 1.87 (P = .07). The relationship between fibrinogen and AMD was J-shaped, with an HR of 2.01 for women in the highest fifth vs second fifth. It was concluded that elevated circulating levels of hsCRP, sICAM-1, and fibrinogen precede the development of visually significant AMD in women, providing further support for the hypothesis that inflammation may play a role in AMD.

VI. CARDIOLOGY

Hypertension, Other Risk Factors and Stroke

According to an article published in the journal Stroke (2007;38:1167-1173), a study was performed to estimate the relationship of high blood pressure values and the 10-year risk of stroke in the Spanish general population aged 60 years or older. The investigation was a multicenter, population-based, cross-sectional study performed in primary care centers. A randomized selection of centers and recruitment population was used. For the study, 7,343 subjects with a mean age of 71.6 years were studied. Study participants included 53.4% females, 34.4% obese subjects, and 27.1% diabetic subjects. Electrocardiographic left ventricle hypertrophy was observed in 12.9% of the subjects, atrial fibrillation in 8.4%, and established cardiovascular disease in 28.9%. Seventy three percent of subjects already had hypertension diagnosed, and 12.8% showed high blood pressure without a prior diagnosis of hypertension. Among hypertensive subjects, 29.1% had high blood pressure on therapeutic objective, and of the total population 35.7% had high blood pressure under control. Results showed that those with hypertension already diagnosed, showed a higher prevalence of other stroke risk factors (left ventricle hypertrophy, atrial fibrillation, diabetes, or established cardiovascular disease). The estimated 10-year stroke risk was 19.6%, and was greater in hypertensive patients (23.7%) than in patients with high blood pressure without known hypertension (12.4%), or in normotensive subjects (5.3%; standard deviation, 0.2; P<0.001). According to the authors, the 10-year estimated stroke risk was 19.6%, and it was greater in hypertensive patients as compared with the remainder people at any blood pressure range. The concomitant stroke risk factors are more prevalent in patients with hypertension already diagnosed, which implies an important additional estimated risk of stroke.

VII. REGULATORY AFFAIRS

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

New Biologic Approved For Purpura Fulminans

Severe congenital Protein C deficiency is a rare genetic defect found in one to two newborns for every million births. Patients with insufficient levels of Protein C experience abnormally high numbers of blood clots. Complete absence of the protein is fatal. Symptoms typically appear soon after birth. Clotting may occur in the blood vessels of the skin, eyes, brain, kidneys and throughout the body. Patients with severe inherited Protein C deficiency must take oral or injected anticoagulant drugs on a regular basis to avoid blood clots. This week, the FDA licensed Ceprotin (Baxter Healthcare Corp), the first biologic treatment for a life-threatening situation from blood clots in the veins, or a severe skin and systemic blood clotting disorder known as Purpura fulminans. Ceprotin is made from the plasma of healthy human blood donors and is a concentrated form of Protein C, a substance normally manufactured in the liver that circulates in the plasma in very small amounts. Protein C plays an important role in controlling blood coagulation by preventing the formation and growth of blood clots. For the development program, the company enrolled all available patients for the pivotal trial. Results showed that Ceprotin was found effective in 94% of the patients studied for Purpura fulminans. In another 6% of patients, the treatment was found effective with complications, because they required a dosage adjustment. The treatments for blood clots in the veins were determined as excellent in 80% of patients and good in 20%. The seven patients who took Ceprotin as a preventive measure before surgery or anticoagulation therapy experienced no blood clotting complications. Eight patients who were given Ceprotin as a long term preventive measure did not experience the severe skin and blood clotting events associated with Purpura fulminans. The most common adverse reactions were rash, itching and lightheadedness. FDA granted Ceprotin orphan drug status, which provides the manufacturer with financial incentives to develop a drug or biologic to treat a rare disease (affecting fewer than 200,000 people in the United States). Since 1983, more than 200 drugs and biological products have been brought to market in this way.

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

VIII. TARGET HEALTH

TARGET HEALTH INC. (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, Web Trials, utilizing Target e*CRF®, our proprietary Internet-based Clinical Trial System, and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team (PADT) assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.

TARGET HEALTH INC.
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Phone: (212) 681-2100; Fax (212) 681-2105

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