Fosteum

Product
Fosteum

Approval Date
June 27, 2007

Release Date
February 14, 2008

Company
Primus Pharmaceuticals

Indication
Dietary management of osteopenia and osteoporosis.

Active Ingredient
Genistein (as aglycone) 27mg, citrated zinc (as bisglycinate) 20mg, cholecalciferol (Vit.D₃) 200IU; caps; lactose-, gluten-free; contains soy.

Agency Roster
S&R Communications Group (professional)
AllOutMarketing (interactive)

Marketing Strategy/Execution
Fosteum, a prescription medical food product, is being positioned to fill a niche that small-molecule drugs may not. That is, the lack of safe, efficient therapy for osteopenia, the precursor to osteoporosis. Beyond lifestyle changes with calcium and vitamin D, many patients and physicians have a lack of options, contends Fosteum marketer Primus Pharmaceuticals. Sciele Pharma will co-promote Fosteum, which is approved for the dietary management of the metabolic processes of osteopenia and osteoporosis. The co-promotion deal enables Primus to leverage Sciele’s women’s health sales force infrastructure. Sciele has a separate specialty sales force to call on OB-GYNs exclusively. Sciele also has a group of sales professionals focused on managed care, and that could be crucial as MCO coverage for this medical food product has been an issue. Another potential challenge in winning the battle in the doctor’s office will be the generic availability of Merck’s Fosamax (alendronate), a widely popular bisphosphonate approved for treating and preventing osteoporosis in postmenopausal women.

The Market

Physician Outlook
Fosteum(tm), a prescription medical food product consisting of genistein (from soy), zinc chelazome (a form of zinc more easily absorbed than other zincs) and cholecalciferol (vitamin D), is indicated for dietary management of osteopenia and osteoporosis. Fosteum should address the need for treatment options that fall in between calcium and vitamin D supplements and the use of drug therapy. Women may find Fosteum an attractive treatment option because it is soy-based and because it does not require sitting or standing for an extended period of time post ingestion, which is a requirement for a number of the currently available prescription osteoporosis treatments. Its twice daily dosing, however, could be somewhat of a drawback and have negative compliance implications.

— Sue Ramspacher, SVP, GfK Market Measures, Feb. 2008

Also in the Pipeline (according to Adis R&D Insight)
No competitor products in phase III or pre-registration, US

Recent MM&M Coverage
Product News
S&R Communications Group

Pharmacology
Fosteum is a specially formulated blend of high purity genistein aglycone from soy, citrated zinc bisglycinate and cholecalciferol (vitamin D₃). It acts by restoring and maintaining the balance of bone turnover toward normal levels in osteopenia and osteoporosis.

Genistein, a soy isoflavone produced from non-GMO soybeans, has shown to reduce osteoclast-mediated bone resorption and stimulate the bone forming activity of osteoblasts by: reversing the effects of estrogen loss by decreasing cytokine production; increasing transforming growth factor ß levels thus decreasing receptor activator of nuclear factor kappa B ligand production; increasing osteoprotegerin (OPG) levels; and decreasing overall osteoclast activity. Genistein has also been shown to reverse early apoptosis of osteoblasts and increase insulin-like growth factor-1 (IGF-1) which increases the number of proto-osteoblasts developed from stem cells resulting in increased recruitment of precursor cells to form osteoblasts.

Zinc is an essential mineral co-factor required by enzymes involved in bone metabolism. It has been shown to work synergistically with genistein and cholecalciferol to improve the absorption of calcium and its deposition into the mineral matrix of bone. The citrated bisglycinate form of zinc has been shown to have improved absorption from the intestine compared to inorganic zinc salts.

Cholecalciferol, the active form of Vit.D₃, regulates calcium and phosphate absorption and excretion as well as bone formation and resorption. Vitamin D deficiency is associated with a negative calcium balance, increased parathyroid hormone levels, bone loss and increased risk of skeletal fracture.

Clinical Trials
Two clinical trials were conducted to assess the efficacy of Fosteum in post-menopausal women with osteopenia or osteoporosis. The first randomized, double-blind, placebo-controlled trial included 389 patients that were either given genistein (n=198) or placebo (n=191). All subjects received calcium (1,000 mg/day) and Vit.D₃ (800 IU/day) in two divided doses. Efficacy was determined by the mean percent change in bone mineral density (BMD) at the 12-month and 24-month mark. A 2.4% and a 5.1% increase in BMD were seen in the femoral neck at 12- and 24-months, respectively, versus a decrease in BMD of 2.2% and 5.3% in the placebo group. Similar results were seen in the lumbar spine BMD where a 2.9% and a 5.8% increase was seen in the genistein group at 12- and 24-months, respectively, versus a decrease in BMD of 3.6% and 6.3% in the placebo group.

In a third year extension of this trial, 138 patients continued on a blinded study that showed further increases in BMD at both the lumbar spine (8.8%) and femoral neck (8.0%). Overall, 85% of the patients in the genistein arm showed increased BMD.

In the second trial, 90 osteopenic or osteoporotic, post-menopausal women were divided into three groups of 30. Patients taking genistein were compared to those on placebo or hormone replacement therapy (HRT). Percentage changes in BMD for the genistein group (femoral neck 3.6%; ward‘s triangle 4.0%; and lumbar spine 3.0%) were generally higher when compared to the HRT (femoral neck 2.4%; ward‘s triangle 3.0%; and lumbar spine 3.8%) and placebo groups (femoral neck -0.7%; ward‘s triangle -0.4%; and lumbar spine -1.6%).

Adverse Reactions
Abdominal and epigastric pain, dyspepsia, vomiting, constipation.

Adults
1 cap twice daily; supplement with calcium and Vit.D₃ as needed.

Children
Not recommended.

Contraindications
History of breast or reproductive organ cancer. Pregnancy. Nursing mothers.

Precautions
Not for treatment of Vit.D deficiency. Women who have 1st degree female relative with history of breast or reproductive cancer. Women capable of becoming pregnant (use adequate contraception). Males: not recommended. Severe hepatic or renal impairment. Conditions associated with overproduction of calcitriol (eg, leukemia, lymphoma, sarcoidosis) or signs/symptoms of Vit.D toxicity; monitor urine and serum calcium. Long-term supplementation or high-doses of zinc-containing products: monitor zinc and copper levels. GI malabsorption; may need higher Vit.D₃ doses (monitor). Ensure adequate calcium and Vit.D₃ intake.

Interactions
Concomitant HRT, SERMs: not recommended. Vit.D₃ absorption may be decreased by bile acid sequestrants, mineral oil, orlistat, olestra. Cimetidine, thiazides, anticonvulsants may increase Vit.D₃ catabolism.