Osteoporosis drug pipeline outlook

[chantell.reagan]

Multiple pharmacologic agents are used for osteoporosis prevention and treatment today. According to the latest treatment guidelines, bisphosphonates are currently recognized to be first-line treatment. Evista (raloxifene), a selective estrogen receptor modulator, is reserved for patients with a greater risk for spine fractures than hip fracture (as its effectiveness in reducing non-vertebral fractures is uncertain). Forteo (teraparatide) should be reserved as second-line therapy for patients at highest risk (with very low BMD, with a previous vertebral fracture). Calcitonin remains an alternative option but with a lower potency than other agents.

There are approximately 8 agents in the near-term pipeline, some which have new mechanisms of actions and none of them are bisphosphonates. It will be interesting to see where they will fit in the place in therapy:

• denosumab is a fully-human monoclonal antibody targeting RANK ligand. It is expected to be reviewed by the FDA by 10/19/09. The latest published Phase III study shows that denosumab is significantly more effective than alendronate in increasing BMD and decreasing bone turnover markers.

• oral selective estrogen receptor modulators (SERMs) - Both Fablyn (lasoxifene) and Viviant (bazedoxifene) should be reviewed in 2009, and are already approved in Europe for treatment of osteoporosis. Aprela (lasoxifene/conjugated estrogen) is currently in Phase III trials and is expected to be filed in 2009. It will be first approved for the management of vasomotor symptoms, but is also being studied for prevention of osteoporosis. Recent two-year data published on arzoxifene (estimated approval in 2011 or later) shows increased BMD at the spine and hip in postmenopausal women and had a neutral effect on the uterus and endometrium.

• Eldecalcitol is an oral active vitamin D3 derivative, expected to be filed in 2009, with approval in late 2010.

• Preos (parathyroid hormone) is another subcutaneous recombinant parathyroid product that is being developed for osteoporosis. Currently, it’s in phase III trials and may not reach the market for another 1-2 years. Of note, in 2007 Preos was granted orphan drug designation for hypoparathyroidsm, it has also been approved in Europe as Preotact.

•Odanacatib has a unique mechanism of action; it is an oral inhibitor of cathepsin K, which is an enzyme involved in bone resorption. It’s currently in Phase III trials.

Sources:

AACE. Osteoporosis Guidelines, Endocr Pract. 2003;9(No. 6)

Institute for Clinical Symptoms Improvement (ICSI). Diagnosis and Treatment of Osteoporosis; 2008

National Institute for Health and Clinical Excellence (NICE). Osteoporosis (primary prevention); 2008

NAMS. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society; Menopause 2006

[chantell.reagan]

Of note, Lilly discontinues its arzoxifene program, due to inability to meet secondary endpoints and questionable safety profile. (source: Lilly press release 8/09)

[Pantablo]

Reclast (zoledronic acid) was not mentioned as an injectable treatment for osteoporosis. Moreover, Reclast is now indicated for the prevention of osteoporosis in post menopausal women (i.e., osteopenia) once every two years. How are plans determning who should receive oral bisphosphonate therapy versus injectable zoledronic acid or risedronate as they injectable forms of the medication can often cost more when considering administration charges and costs?

[chantell.reagan]

There seems to be a trend for plans to require failure/intolerance/contraindication to at least 1 oral bisphosphonate before an injectable agent (i.e. Boniva, Reclast) is approved. For a more detailed analysis, please note that we previously provided Reclast policy criteria in April 2009, comparing 7 regional and national plans. Since the expanded indication for prevention of osteoporosis for Reclast is relatively new (June 2009), most of the policies have not been updated yet to reflect this change.