Elestrin

Product
Elestrin

Approval Date
December 15, 2006

Release Date
May 25, 2007

Company
Kenwood Therapeutics

Class
Estrogen

Indication
Moderate-to-severe vasomotor symptoms associated withmenopause.

Active Ingredient
Estradiol 0.06%; gel; contains alcohol.

Agency Roster
Bradley Pharmaceuticals (In-house creative and PR)

MarketingStrategy/Execution
Elestrin is beinglaunched by the Kenwood division of Bradley Pharmaceuticals following a December2006 approval for treating hot flashes. Bradley hired 60 reps to pitch the low-doseestrogen gel to the 14,000 OB/GYNs in the US. A launch meeting for editors inNew York City, arranged by PR agency Sharp Communications, resulted in a piecein the New York Times on low-doseestrogen therapy, an issue which has gained greater prominence since the 2002Women’s Health Initiative study detailed health risks associated with estrogentherapy. A representative from Bradley said journal ads are planned, but no DTCpromotion at this time. The company estimates the topical market segment aloneat $300 million.

The Market

Physician Outlook
Study planned, 2008

Also in the Pipeline(according to Adis R&D Insight)
Drug: Aprela
Manufacturer: Ligand Pharmaceuticals/Wyeth
Indication: Postmenopausal osteoporosis prevention, Vaginalatrophy, Vasomotor symptoms
Active Ingredient: Conjugated estrogens/bazedoxifene
Phase: III
Source: Wolters Kluwer Health, Oct. 2007

Recent MM&MCoverage

Specialtyfirm adding reps for hot-flash gel

Bradleybeefs up reps for launch

Company news

Pharmacology
The addition of exogenous estrogens, such as Elestrin, helps to alleviatethe vasomotor symptoms associated with declining estrogen levels. Elestrincontains 0.06% estradiol in a hydro-alcoholic gel base. One pump actuationdelivers 0.87g, which provides systemic delivery of 0.0125mg of estradioldaily. The 1.7g dose, two pump actuations, provides systemic delivery of0.0375mg daily. After applying Elestrin to the upper arm, steady state serumconcentrations are achieved in about three days.

Application of sunscreen 10 minutes before application of Elestrinincreased exposure to estradiol by 55%. Concomitant sunscreen application forseven days increased estradiol exposure by 2-fold, regardless of when sunscreenwas applied.

Clinical Trials
The efficacy of Elestrin was evaluated in a 12-weekdouble-blind, placebo-controlled trial involving 484 postmenopausal women 28–74years of age who had at least 60 moderate-to-severe hot flushes per week atbaseline. Patients applied Elestrin 0.87g (0.52mg estradiol), 1.7g (1.02mgestradiol), 2.6g (1.56mg), or placebo once daily to the upper arm. Reduction inboth the frequency and severity of hot flushes was statistically significant atweek 4 for the Elestrin 1.7g/day dose, and week 5 for the Elestrin 0.87g/daydose when compared to placebo. Both the 0.87g/day and 1.7g/day doses were statisticallysignificant compared to placebo at week 12

Adverse Reactions
See literature. Breast tenderness, metrorrhagia, vaginaldischarge, nausea, nasopharyngitis, upper respiratory tract infection.Long-term use may increase risk of estrogen-dependent cancers (eg, breastand/or endometrial), dementia, others. Increased risk of thromboembolicdisorders, gallbladder disease.

Adults
Prime pump before 1st use. Use lowest effective dose.Initially: Apply 1 pump (0.87g) daily to clean, dry, unbroken skin of upperarm. Reevaluate periodically.

Children
Not applicable.

Contraindications
Undiagnosed abnormal genital bleeding. Thromboembolicdisease (eg, stroke or MI within past year, DVT, pulmonary embolism).Thrombophlebitis. Breast or estrogen-dependent carcinoma. Liver dysfunction ordisease. Pregnancy (Cat X).

Precautions
Increased risk of endometrial carcinoma or hyperplasia inwomen with intact uterus (adding progestin is essential). Renal dysfunction.Gallbladder disease. Hypertriglyceridemia. Hypothyroidism. Conditionsaggravated by fluid retention. Bone disease associated with hypercalcemia. Doinitial complete physical; repeat annually (include BP, mammogram, PAP smear).Discontinue if jaundice occurs and during immobilization or 2 weeks beforeplanned mammogram or surgery associated with thromboembolism. Product isflammable. Nursing mothers.

Interactions
May be antagonized by CYP3A4 inducers. May be potentiated byCYP3A4 inhibitors. Avoid applying sunscreen to application site (increasesestradiol absorption).