(complimentary Newsletter from Target Health Inc.)

Saturday, December 6, 1997

We would like to welcome our colleagues David Clark (Compliance Specialists Inc.), Karen Hammond (UAB), Rakesh Rughabanshi (Ferring Pharmaceuticals), Steve Fortunato (Proterm Inc.), Susan Slezak (Micropulse Inc.), Charlotte Lieb (Micropulse Inc.), Melinda Tully (Micropulse Inc.), Helen Jagielo (Micropulse Inc.), Gerry Montmorency (consultant) and Dennis Ferrero (Stockton, CA Board of Health). Please forward ON TARGET to your friends and colleagues so that they may be added to our unique and proprietary e-mail list.

TARGET HEALTH NEWS

TARGET HEALTH is pleased to announce the appointment of Anita Islam, Ph.D. as Manager of Clinical Research. Anita holds a Ph.D. in neurobiology with strong experience in clinical psychology and opiod receptors. In her first two weeks at TARGET HEALTH she has already completed the first draft of an IND in Women's Health. Anita will take charge of TARGET HEALTH's clinical operation and will add an exciting dimension in TARGET HEALTH's continuing growth.

The FDA has ordered that folic acid be added to all food grains by the start of the year. The proposed dose will most likely be 140 mcg/100 g of grain. The rationale behind the addition of folic acid to the diet is based on the results of previous studies showing that daily doses of folic acid can prevent neural tube birth defects and that few women of childbearing age followed the recommendations on folic acid. About 4,000 women in the United States become pregnant annually with babies having neural tube defects. Folic acid occurs naturally in leafy vegetables like spinach and in orange juice and liver.

A study just published in the Lancet has suggested that adding even a small amount of folic acid to women's diets in their childbearing years should sharply reduce brain and spinal cord birth defects. The study concluded that dosages as small as 100 mcg of folic acid per day could reduce the number of such birth defects by about 22 percent. Dosages of 400 mcg cut the defects by about 47 percent.

In the Lancet study, blood levels of folate were monitored in 100 women of childbearing age in Dublin. Four groups of women were studied: the control group received no folic acid, while the other groups received doses of 100, 200 or 400 mcg daily. After six months, women on the 100-microgram dosage achieved a blood level of folate that, based on previous studies, would prevent 22 percent of neural tube birth defects. Those on 200-microgram doses achieved a 41 percent prevention level, while those on the 400-microgram dose had a 47 percent prevention level. Folate declined in the blood of women not taking the vitamin.

TARGET HEALTH is actively involved in several women's health projects which are on both NDA (2) and PMA (1) tracks. An additional project in high-risk pregnancy is at the early development stage but with very sound science and medicine.

The "non-estrogenic" estrogen, raloxifene (Evista, ELI LILLY & CO), has recently been endorsed by a federal advisory panel. The advisory panel voted 8-4 to recommend approval of raloxifene. The panel noted that although the drug was not as effective in building bone as estrogens currently used by postmenopausal women, it lacked worrisome growth stimulation of the breast and uterus that can result from treatment with these natural estrogens. If the drug is cleared for marketing by the FDA, it is expected to cause an increase in the number of post-menopausal women willing to take hormones to prevent osteoporosis and possibly heart disease. Currently, less than 1 in 5 post- menopausal women take hormone replacement which has been linked to an increased risk of cancers of the breast and endometrium.

In a study recently reported in The New England Journal of Medicine, approximately 600 postmenopausal women from eight European countries were randomly assigned to treatment with one of three doses of raloxifene placebo for two years. Those receiving raloxifene experienced increases in bone density of their lower spine, hip and total body along with a drop in blood levels of LDL cholesterol.

Raloxifene is the second of a new class of synthetic estrogenic compounds that have selective actions on different tissues. The first to reach the market, tamoxifen, blocks the ability of natural estrogens to stimulate growth of breast tissue. It is now widely used in women who have had breast cancer to prevent cancer in the second breast. Tamoxifen also decreases the risk of heart attack by lowering cholesterol levels in the blood. However, it can cause cancer of the endometrium.

Both tamoxifen and raloxifene take advantage of the discovery that estrogen receptors behave differently in different tissues, depending on the nature of the estrogenic compound that hooks up with them. It is not yet known whether raloxifene, like natural estrogens, will decrease the tendency of the blood to form circulation-blocking clots. And still unexplored is whether raloxifene can prevent or slow the progression of Alzheimer's disease.

The FDA announced new steps to provide health care professionals with the information necessary to prescribe medications more safely for children. The new measures are designed to eliminate unnecessary risks faced by children and adolescents aged 16 and under when treated with drugs primarily tested in adults. TARGET HEALTH is involved in pediatric studies in Cystic Fibrosis and Cholestatic Liver Disease and have available several excellent sites for pediatric trials.

The vast majority of prescription drugs currently on the market lack information about appropriate use in children. A key element is amending a 1979 regulation that required full clinical trials in the pediatric population as a basis in labeling for use in children. That rule is being amended to allow companies, in some situations, to extrapolate from adult studies and use that information -- along with other information about use of the drug in children -- to provide labeling information on the appropriate use in children. In addition, CDER is taking steps to increase the number of pediatric studies included in NDA submissions.

The new rule, revises the "Pediatric Use" subsection of prescription drugs labeling and makes it easier, in some situations, for manufacturers to include pediatric information on the label of their prescription products. One of the rule's key provisions sets forth the conditions under which the agency permits pediatric use statements based on adequate and well-controlled studies in adults together with other information, such as pharmacokinetic and safety data, that supports pediatric use. The rule makes clear that such pediatric use statements can be made only if the course of the disease and the drug's effects are sufficiently similar in the pediatric and adult populations to permit extrapolation from the adult data to pediatric patients. Under the new rule, manufacturers also must reexamine existing information to determine whether the pediatric labeling of their marketed products can be modified on the basis of adult studies and Pediatric Labeling other available data. If so, they have to submit an application for supplemental labeling within two years. One of TARGET HEALTH's areas of expertise is Drug and Device Regulatory Affairs. TARGET HEALTH interacts with the FDA on behalf of many of its clients and has almost daily contact with the Agency.

Finally, the new regulation clarifies that the agency has the authority to request specific pediatric use information. For example, FDA may decide to request pediatric use data for a drug that is widely used, represents a safety hazard or is therapeutically important in the pediatric population. The rule, however, does not limit the manner in which a practitioner may prescribe an approved drug. The additional measures will include the establishment of a special pediatric subcommittee that will track the implementation of the new regulations and draft policies and guidance documents to ensure that the possibility of pediatric testing and use are explored during the development of new drugs. The agency also will work closely with the Pediatric Pharmacology Research Units that are funded by the National Institute of Child Health and Human Development to conduct pediatric studies on selected therapies. Finally, FDA will work with sponsors on investigational new drug applications and on new marketing applications to ensure that necessary pediatric data are included for products that have a potentially widespread use in children.

TARGET HEALTH INC. is a full service CRO with staff dedicated to all aspects of Regulatory Affairs, Clinical Research, Biostatistics, Data Management, Strategic Planning and Drug and Device Development. TARGET HEALTH INC. also has a group of specialized advisors in the areas of Toxicology, Analytical Methods Validation, Product and Process Development, Quality Assurance, Manufacturing and Animal Health.

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TARGET HEALTH INC.
310 Madison Avenue, 22nd Floor, New York, NY 10017
Phone (212) 681-2100 - Fax (212) 682-0151

JulesMitchel@targethealth.com (Dr. Jules T. Mitchel, President)
JoyceHays@targethealth.com (Ms. Joyce Hays, CEO)