Drug Updates

Denosumab as a treatment for osteoporosis was the topic of discussion at an FDA advisory committee meeting on August 13, 2009.¹³ Safety issues were the main cause for concern with this agent. Most at the meeting agreed that it should be approved for the treatment of osteoporosis in postmenopausal women for those who have failed other treatments, at least until long-term safety data are available. Panelists were also in favor of initial approval to treat bone loss in men with prostate cancer undergoing hormone ablation therapy. Potential safety issues include tumor metastates and endocarditis. Hence, approval for other treatments may not happen until later, if at all. A boxed warning or a risk evaluation and mitigation strategy (REMS) is likely for denosumab, once approved. Post-approval studies will be conducted. Denosumab advantages include bi-yearly subcutaneous administration, superiority in fracture prevention, and clinical trial program involving more than 20,000 patients worldwide for different indications. A final decision on the osteoporosis indications is expected by October 19, 2009 (the Prescription Drug User Fee Act date).¹⁴

Denosumab advantages include biyearly subcutaneous administration, superiority in fracture prevention, and clinical trial program involving more than 20,000 patients worldwide for different indications. Because there have been newer concerns about long-term side effects of bisphosphonates (including osteonecrosis of the jaw), this may improve the outlook for a positive decision for denosumab’s approval first for osteoporosis and subsequently for other indications.

Oxycodone/niacin tablets (Acurox) has received a complete response letter from the FDA regarding its NDA. The letter raises issues regarding the potential abuse deterrent benefits of this combination product. The proposed use of oxycodone/niacin is in the treatment of moderate to severe pain, it has been scheduled a C-II. It was developed using an aversion technology designed to deter the intentional swallowing of excessive doses, IV injection of dissolved tablets, and/or snorting of crushed tablets. The original NDA was accepted earlier this year with a priority review designation.¹⁵

Pegloticase (Krystexxa) received a recommendation for marketing approval by the Arthritis Advisory Committee of the FDA.16 Pegloticase is a biologic, PEGylated, uricase enzyme, evaluated for the treatment of refractory chronic gout. Of concern were safety issues related to cardiovascular complications.¹⁶

Michele Kaufman is a freelance medical writer based in New York City.

References

1. Reinberg S. FDA report urges tougher acetaminophen warning. http://healthday.com/printer.asp?AID=627508. Published May 28, 2009. Accessed July 28, 2009.
2. Farrell SE. Toxicity acetaminophen. http://emedicine.medscape.com/article/820200-overview. Published October 3, 2007. Accessed July 28, 2009.
3. June 29–30, 2009: Joint Meeting of the Drug Safety and Risk Management Advisory Committee with the Anesthetic and Life Support Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee: Meeting announcement. www.fda.gov/AdvisoryCommittees/Calendar/ucm143083.htm. Published July 7, 2009. Accessed July 28, 2009.
4. El-Hinnawy P. FDA requires labeling change for some drugs used to prevent kidney rejection of kidney transplants. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm171775.htm Published July 15, 2009. Accessed July 28, 2009.
5. Information for healthcare professionals: Varenicline (marketed as Chantix) and bupropion (marketed as Zyban, Wellbutrin, generics) FDA Alert. www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm169986.htm. Published July 1, 2009. Accessed July 27, 2009.
6. FDA Web site: Varenicline (marketed as Chantix) and bupropion (marketed as Zyban, Wellbutrin, and generics). www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm170090.htm. Published July 1, 2009. Accessed July 27, 2009.
7. Cadence Pharmaceuticals announces priority review and acceptance of NDA submission for Acetavance for treatment of acute pain and fever. www.drugs.com/nda/acetavance_ 090715 .html. Published July 15, 2009. Accessed July 27, 2009.
8. Dennis M. Celgene’s apremilast improved symptoms of psoriatic arthritis in mid-stage trial. www.firstwordplus.com/Fws.do?articleid=A3E421298FFD43BEA1FD64C6E5DE39BA&logRowId=311088. Published June 16, 2009. Accessed July 28, 2009.
9. Celgene announces positive top line data from randomized controlled phase ii study of Apremilast in psoriatic arthritis. http:// ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=1299205&highlight=. Published June 15, 2009. Accessed July 28, 2009.
10. AstraZeneca submits NDA for low dose aspirin/esomeprazole combination product. Also submits supplemental new drug application (sNDA) for NEXIUM capsules for risk reduction of low-dose aspirin-associated peptic ulcer disease. www.astrazeneca-us.com/about-astrazeneca-us/newsroom/all/5762542?itemId=5762542. Published May 4, 2009. Accessed July 27, 2009.
11. Human Genome Sciences and GlaxoSmithKline announce positive phase 3 study results for Benlysta in systemic lupus erythematosus. www.gsk.com/media/pressreleases/2009/2009_pressrelease_10074.htm. Published July 20, 2009. Accessed July 27, 2009.
12. Todoruk M. Long-term data for GlaxoSmithKline, Human Genome’s lupus drug presented at EULAR. www.firstwordplus.com/Fws.do?articleid=801205B919DB4990981A76569BCACD93. Published June 11, 2009. Accessed July 27, 2009.
13. Dimond P. Denosumab—great expectations for Amgen and Osteoporosis Market. www.genengnews.com/specialreports/sritem.aspx?oid=57062429. Published June 26, 2009. Accessed July 27, 2009.
14. Boggs J. Split Panel Vote Takes Shine off Denosumab: Is PMO Only So-So? www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=51802. Published August 17, 2009. Accessed August 18, 2009.
15. Acura and King receive FDA complete response letter regarding Acurox. www.kingpharm.com/Investors/News_Details.cfm?news_item_id=519. Published July 2, 2009. Accessed July 27, 2009.
16. FDA Appointed Arthritis Advisory Committee Recommends U.S. Food and Drug Administration Approval for KRYSTEXXA(TM) for Refractory Chronic Gout. http://investor.savient.com/ReleaseDetail.cfm?ReleaseID=390150. Published June 16, 2009. Accessed July 27, 2009.
17. Bratulic A. FDA panel recommends approval of Savient’s Krystexxa. www.firstwordplus.com/Fws.do?articleid=2AFF4DD597D24220887613900343426C&logRowId=311087. Published June 16, 2009. Accessed July 27, 2009.
18. FDA approves Zipsor. www.drugs.com/newdrugs/xanodyne-receives-approval-u-s-food-administration-zipsor-diclofenac-potassium-liquid-filled-1469.html. Published June 17, 2009. Accessed August 7, 2009.
19. Xanodyne receives approvable letter from the U.S. Food and Drug Administration for Zipsor (diclofenac potassium) capsules. www.xanodyne.com/newsroom_details.asp?NewsId=48. Published July 22, 2009. Accessed August 7, 2009.
20. Facts and Comparisons. www.factsandcomparisons.com/News/ArticlePage.aspx?cat=update&id=8448. Published July 27, 2009. Accessed August 7, 2009.
21. New drug is first injectable product approved for sale in the United States for treatment of pain and fever. www.drugs.com/newdrugs/cumberland-pharmaceuticals-announces-fda-approval-caldolor-1447.html. Published June 11, 2009. Accessed August 7, 2009.
22. Nucynta. www.empr.com/nucynta/drugproduct/69. Published July 2, 2009. Accessed July 27, 2009.
23. New Drug: Nucynta (tapentadol). Pharmacist’s Letter/Prescriber’s Letter 2009;25(7):250711.