News Release About Fosamax

SAN DIEGO, CA -- June 15, 1999 -- The results of a one-year study show Fosamax® (alendronate sodium; Merck) tablets produced significantly greater increases in bone mineral density (BMD) at both the spine and hip than Miacalcin® (calcitonin-salmon; Novartis) nasal spray in patients postmenopausal osteoporosis. This was the first clinical study to compare the recommended treatment dosages for these two drugs.

The effect of calcitonin nasal spray on BMD was not significantly different at the spine or hip trochanter from the effect of a placebo tablet. At the femoral neck of the hip, calcitonin maintained BMD at the baseline level. BMD currently is the most accurate predictor of fracture risk from osteoporosis. "Fosamax tablets and calcitonin nasal spray are two of the most commonly prescribed treatments for osteoporosis in postmenopausal women, but there have not been any head-to-head studies comparing recommended dosages of the two products," said Robert Downs, M.D., professor of medicine, Virginia Commonwealth University's Medical College of Virginia. Dr. Downs presented the findings from his study at the 81st Annual Meeting of the Endocrine Society, ENDO 99. "This one-year study was designed to compare the efficacy of the two products and to assess tolerability." These comparative results need to be confirmed in other studies," he added. Fosamax is indicated in postmenopausal women for the prevention and treatment of osteoporosis, and for the prevention of fracture in postmenopausal women with osteoporosis. Calcitonin nasal spray is indicated for the treatment of postmenopausal osteoporosis in women more than five years post-menopause who refuse or cannot tolerate estrogens or in whom estrogens are contraindicated. The first year of the study included 299 postmenopausal women with osteoporosis and was conducted at 24 centers in the US. The study was designed as a one-year study (12 months) with a one-year extension (24 months total). During the second year, the alendronate placebo arm will be discontinued and all patients will receive either open-label Fosamax tablets or calcitonin nasal spray. The study was funded by Merck & Co., Inc. Women in the study were randomized to receive either Fosamax (10 mg once-daily, N=118), alendronate placebo (N=58), or open-label calcitonin nasal spray (200 IU once-daily, N=123) for one year. Administration of Fosamax or placebo was double-blinded; the pills were administered according to dosing instructions for Fosamax. The marketed form of calcitonin nasal spray was administered open-label. Intranasal placebo was unavailable for the study. Per standard medical practice, patients were supplemented with vitamin D and calcium.

All patients were given 400 IU vitamin D daily and a calcium supplement, if necessary, to ensure a daily intake of at least 1,000 mg elemental calcium. BMD was measured by dual x-ray absorptiometry at baseline, six months and 12 months. The primary endpoint of the study design was BMD of the lumbar spine at 12 months. Treatment groups were of sufficient size to detect a 2 percent difference in efficacy between Fosamax and calcitonin nasal spray (statistical power greater than 90 percent). Secondary endpoints for the study include: hip trochanter and femoral neck BMD at 12 months; lumbar spine, hip trochanter and femoral neck BMD for up to 24 months; and biochemical markers of bone turnover for up to 24 months. Safety and tolerability were assessed throughout the study by periodic physical exams, laboratory evaluations and reporting of adverse events. Patient compliance was assessed using patient reporting and study coordinator evaluation of medication usage. There were no differences of statistical significance in the compliance rates between the three treatment groups. The patients enrolled in the study were 45 to 84 years of age (average age 64 years) and were at least five years post-menopause (16 years post-menopause on average). There were no significant differences between treatment groups in terms of other risk factors for osteoporosis including race, age, caffeine intake, smoking history, family history of osteoporosis or dietary calcium intake. At the end of one year, Fosamax produced significantly greater increases in BMD than calcitonin nasal spray at both the lumbar spine (primary endpoint) and hip (secondary endpoints). A significant difference in BMD in the group treated with Fosamax, as compared to the group treated with calcitonin nasal spray, was observed at the lumbar spine and hip trochanter as early as the first measurement at six months, and persisted at the 12-month measurement. At 12 months, a significant increase in BMD also was seen at the femoral neck of the hip with Fosamax as compared to calcitonin nasal spray. In the calcitonin nasal spray group, BMD changes at the lumbar spine and hip trochanter were not statistically different from placebo at any point in the study. At the femoral neck of the hip, the calcitonin group demonstrated a statistically significant difference in BMD relative to placebo, while the placebo group experienced a loss of BMD at the femoral neck.

Changes in BMD at 12 months relative to baseline were as follows: -- At the lumbar spine (primary endpoint), there was a statistically significant 5.2 percent increase in BMD from baseline in the treatment group receiving Fosamax, a statistically significant 1.2 percent increase in the calcitonin group, and a non-significant 0.2 percent increase in the group receiving placebo. -- At the hip trochanter, BMD was significantly increased by 4.7 percent from baseline in the group treated with Fosamax, the group treated with calcitonin had a non-significant 0.5 percent increase, and there was a 0 percent change with placebo. -- At the femoral neck of the hip, there was a significant 2.8 percent increase in BMD from baseline in the treatment group receiving Fosamax, a non-significant 0.6 percent increase with calcitonin, and a significant 1.3 percent decrease with placebo. Fosamax Well-Tolerated

Fosamax was generally well-tolerated in the study. These findings are consistent with prior clinical studies with Fosamax. Adverse experiences related to the gastrointestinal (GI) tract were reported more commonly in both the blinded groups treated with Fosamax and alendronate placebo than in the group given open-label calcitonin nasal spray. Respiratory and nasal adverse experiences were reported more commonly in the calcitonin nasal spray group. "The safety profiles of these products are well documented in clinical trials; both are tolerated well when dosed properly," said Dr. Downs. "In this comparative study we saw that Fosamax was not only well-tolerated, but it also had significantly greater efficacy than calcitonin nasal spray.

ENBREL

Painful, Disabling Disease Affects More Than 250,000 People in U.S.

SEATTLE, Aug. 16 /PRNewswire/ -- Immunex Corp. (Nasdaq: IMNX) announced today that clinical trial results indicate that psoriatic arthritis patients treated with ENBREL(R) (etanercept)experienced improvement in the signs and symptoms of their disease and an increase in their functional ability compared to patients who were treated with placebo.

The results of this study were announced today after the trial was unblinded. The study's lead investigator, rheumatologist, Philip Mease, MD in association with dermatologist, Ben Goffe, MD, conducted the three month double-blind study in 60 patients to test the effects of ENBREL in psoriatic arthritis.

Psoriasis is a skin disorder that is estimated to affect 2.5 to 5 million Americans. The disease most commonly appears as inflamed swollen skin lesions that can become extremely painful and disfiguring. Psoriatic arthritis is a specific type of arthritis that occurs in approximately five to seven percent of the people who have psoriasis and is usually diagnosed between the ages of 30 and 50. This disease is characterized by pain, swelling and stiffness, primarily in the hands, feet or in larger joints such as the knees, hips, elbows, and the spine. There are currently no therapies approved by the U.S. Food and Drug Administration (FDA) for the treatment of people with psoriatic arthritis. "The pain and swelling of psoriatic arthritis, coupled with the painful, unpleasant and unsightly symptoms of psoriasis make this disease very difficult to treat and to live with," said Dr. Mease. "It is important to continue to study innovative new approaches to treating psoriatic arthritis like ENBREL."

In this trial ENBREL was generally well tolerated. The most common adverse events reported were mild injection site reactions and respiratory tract infections. There were no significant differences in the rate of occurrence of side effects between the treatment groups. A formal presentation of the data from this ENBREL study will occur at a forthcoming scientific meeting. The results of this trial will be the basis for discussion with the FDA concerning the filing of a supplemental biologics license application (sBLA) for an expanded label for ENBREL in psoriatic arthritis.

This study was conducted in 60 patients with severe psoriatic arthritis who were randomized to receive either 25 mg twice-weekly subcutaneous injections of ENBREL or placebo for three months. The patients in this study had severe psoriatic arthritis at study entry with a mean of 24 tender and 17 swollen joints. The endpoint for the study was defined as a 30 per cent improvement of at least two of four criteria: physician and patient global assessment and joint tenderness and swelling without a 30 per cent worsening of any of the criteria. An additional measure of treatment response was ACR 20, modified for psoriatic arthritis, which additionally includes patient responses to the Health Assessment Questionnaire (HAQ), pain evaluation and acute phase reactants. Patients with psoriasis that affected greater than three percent of their body surface area at the beginning of the study were evaluated with skin assessments using the Psoriasis Area and Severity Index and target le! sion assessment.

All patients participating in the double-blind segment of the study, including those in the placebo arm, may continue for six-months in an open-label trial of ENBREL. ENBREL belongs to a new class of drugs known as biologic response modifiers, and is an entirely new approach to the study of psoriatic arthritis. ENBREL acts by binding tumor necrosis factor (TNF). The binding of ENBREL to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity. ENBREL is currently being studied in several diseases where overproduction of TNF plays a role.

Additional information about psoriatic arthritis and psoriasis can be found on The National Psoriasis Foundation web site ( http://www.psoriasis.org ) or by calling toll-free (800-723-9166). The results described herein are based on investigational data analyzed by Immunex. These data have not been reviewed by the U.S. Food and Drug Administration (FDA) as part of an application for regulatory approval. ENBREL is not indicated for the treatment of psoriatic arthritis or psoriasis.

IN POSTMARKETING USE, SERIOUS INFECTIONS AND SEPSIS, INCLUDING FATALITIES, HAVE BEEN REPORTED. MANY OF THESE EVENTS OCCURRED IN PATIENTS PREDISPOSED TO INFECTIONS, SUCH AS THOSE WITH ADVANCED OR POORLY CONTROLLED DIABETES. DISCONTINUE ENBREL IN PATIENTS WITH SERIOUS INFECTIONS OR SEPSIS. DO NOT START ENBREL IN THE PRESENCE OF SEPSIS, INFECTION (INCLUDING CHRONIC OR LOCALIZED), OR ALLERGY TO ENBREL OR ITS COMPONENTS. USE CAUTION IN PATIENTS PREDISPOSED TO INFECTION. The most frequent adverse events in adult clinical trials in rheumatoid arthritis (n=349) were injection site reactions (ISR) 37%, infections (35%) and headache (17%). Malignancies were rare (<1%). Only the rate of ISR was higher than placebo. Immunex manufactures ENBREL. Immunex and Wyeth-Ayerst market ENBREL in North America. Other Wyeth-Ayerst affiliates will market ENBREL outside of North America. Additional information about ENBREL, including full prescribing information, can be found on the company-sponsored web site at (www.ENBREL.com) or by calling toll-free 888-4ENBREL (888-436-2735). Immunex is a biopharmaceutical company dedicated to developing immune system science to protect human health. The company's products offer hope to patients with cancer, inflammatory and infectious diseases. American Home Products Corporation's Wyeth-Ayerst division is a major research-oriented pharmaceutical company with leading products in the areas of women's health care, cardiovascular disease therapies, central nervous system drugs, anti-inflammatory agents, vaccines and generic pharmaceuticals. American Home Products owns a majority interest in Immunex. AHP is one of the world's largest research-based pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of prescription drugs and over-the-counter medications. It is also a leader in vaccines, biotechnology, agricultural products and animal health care.

NOTE: This release contains forward-looking statements that involve risks and uncertainties, including risks associated with clinical development, regulatory approvals, patent litigation, product commercialization and other risks described from time to time in the SEC filings by Immunex and American Home Products respectively, including the most recently filed 10-K and 10-Q forms. For more information, please refer to www.immunex.com.

TELANGIECTASIA

Dilated superficial blood vessels, which may be seen in Rosacea or certain systemic diseases (ataxia-Telangiectasia, Scleroderma) and may result from long-term therapy with topical fluorinated corticosteroids, but for most, the cause is unknown.

" The Merck Manual Syllables: tel•an•gi•ec•ta•sia Pronounced something like this: te-lan-jee-ek-taa-zsha Singular: telangiectasia Plural: telangiectasias or telangiectases. Adverb: telangiectatic Meaning: An abnormal dilatation of capillary vessels and arterioles that often forms an angioma. Angioma: A tumor composed chiefly of blood vessels or lymph vessels. Merriam Webster's Collegiate Dictionary Telangiectasia may appear on the hands or face. They appears as tiny round red spots the size of a head of a pin that disappear with pressure these are "mat-like Telangiectasia" and are typical of CREST scleroderma. These tiny red dots, which are caused by blood vessels dilating near the surface of the skin. Some people have more of a spidery look to their skin and very small dots and others may have very large and pronounced dots. There is no health problem with these They are only a cosmetic nuisance.

Excerpted with permission from Dr. Szarnicki's Venous Disease Page http://www.veins-szarnicki.com/venous.html#te lang Telangiectasias are similar to spider veins but occur primarily on the face, neck and upper chest. They are most common around the nose and on the cheeks. They may appear as red, blue or purple vessels matted together. These blood vessels are abnormal and serve no essential function and therefore can be very safely removed. The cause of these abnormal blood vessels is unknown but they seem to be most prevalent in people with facial flush or blush, or those with excessive sun exposure. Other associated aggravating factors include Rosacea (an adult form of acne), ingestion of hot or spicy foods, exercise, hormone level fluctuations, steroid medications, and more rare skin diseases such as scleroderma (systemic sclerosis) or CREST. Telangiectasia is the T in CREST

Telangiectasias can be covered with makeup or a dermatologist can remove it with sclerotherapy, laser, or PhotoDerm. However, "Second Generation" Telangiectasia is often resistant to treatments Many use Dermablend to cover the Telangiectasias. This product is available in most fine stores in your local mall. I found it at our local Hecht's. http://www.sheen.com/derma/dblend.htm Also see Makeup Magic for more information. http://www.sclerodermasupport.com/adaptation/ skincare.htm#makeupmagic