Other adverse effects in odanacatib-treated patients included 92 individuals who developed atrial fibrillation compared with 80 placebo-treated patients. Stroke was also more common in odanacatib-treated patients (n=109 [1.4%] vs. n=86 [1.1%]), and atypical femoral shaft fractures (n=5 [1.1%] vs. none for placebo-treated patients). The NDA is anticipated to be submitted in 2015.5
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TNX-102 SL (cyclobenzaprine HCl 2.8 mg sublingual) is a sublingual pain management agent being investigated to treat fibromyalgia.6 In the recent Phase 2b BESTFIT (BEdtime Sublingual TNX-102 SL as Fibromyalgia Intervention Therapy) trial as a chronic bedtime fibromyalgia treatment, TNX-102 failed to meet the main goal of reducing patient pain by Week 12 of the study. Fibromyalgia patients did, however, have improved sleep quality while taking the agent, with a small amount (30%) experiencing pain reduction. The manufacturer is regrouping and may plan trials around TNX-102 to focus on sleep quality improvement as an indication rather than pain management. Another potential use is in treating post-traumatic stress disorder, potentially by enhancing sleep quality, as well.
Atypical fractures continue to be associated with bisphosphonates.7 According to Schilcher et al in their recent cohort analysis of long-term bisphosphonate use, for patients with osteoporosis, the benefits of bisphosphonate treatment outweigh the risk during the first years of treatment. However, for patients without osteoporosis and with only a moderate BMD decrease, the benefit of bisphosphonate use is likely to be smaller than the risk. Their team evaluated radiographs from over 5,300 men and women aged 55 years and older who had a femoral shaft fracture. Of these, 172 had atypical fractures according to the American Society for Bone and Mineral Research criteria (women: 160, men: 12).
The age-adjusted relative risk of an atypical fracture with bisphosphonate use was 55% and 54% among women and men, respectively. Among women the absolute and relative risks were three times higher than in male bisphosphonate users. Fracture risk among women increased with longer duration of bisphosphonate use. The multivariable-adjusted odds ratio with four to five years of current use was 100 times higher than with nonuse. Use of glucocorticoids or proton pump inhibitors along with bisphosphonates did not modify the risk of atypical fractures. In the patients with atypical fracture, bisphosphonate agents included alendronate (n=120), risedronate (n=16) and ibandronate (n=2).
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- Flexion Therapeutics Inc. Flexion Therapeutics announces clinical hold of FX006 Phase 2b clinical trial in osteoarthritis of the knee. Press Release. Sept. 17, 2014. http://ir.flexiontherapeutics.com/releasedetail.cfm?ReleaseID=871411.
- Flexion Therapeutics Inc. Flexion Therapeutics to start FX006 Phase 3 pivotal trial in 2014; Following FDA meeting, development plan advanced by one year. Press Release. Sept. 3, 2014. http://ir.flexiontherapeutics.com/releasedetail.cfm?ReleaseID=868967.
- Barber J. Merck & Co.’s osteoporosis drug odanacatib hits main goal in Phase III study. First Word Pharma. Sept. 15, 2014. http://www.firstwordpharma.com/node/1235141#axzz3DUBpT59Y.
- Mayo Clinic staff. Diseases and conditions: Morphea. Mayo Clinic. Oct. 5, 2012. http://www.mayoclinic.org/diseases-conditions/morphea/basics/definition/con-20028397.
- Merck announces data from pivotal Phase 3 fracture outcome study for odanacatib, an investigational oral, once-weekly treatment for osteoporosis. Press Release. Sept. 15, 2014. http://www.mercknewsroom.com/news-release/research-and-development-news/merck-announces-data-pivotal-phase-3-fracture-outcomes-st.
- Tonix Pharmaceuticals Holding Corp. Tonix Pharmaceuticals reports top line results from Phase 2b BESTFIT Trial of TNX-102 SL in patients with fibromyalgia. Press Release. Sept. 29, 2014. http://content.stockpr.com/_news/tonixpharma/2014-09-29_Tonix_Pharmaceuticals_Reports_Top_Line_Results_Fro_854.pdf.
- Schilcher J, Koeppen V, Aspenberg P, et al. Risk for atypical femoral fracture during and after bisphosphonate use. N Engl J Med. 2014;371:974–976.