Update on Drugs - May 2008

Triphendiol
(formerly NV-196)
Marshall Edwards, Inc.

The US FDA granted orphan drug status to this multiple signal transduction regulator (MSTR) in February 2008 for the treatment of Stage IIB to Stage IV malignant melanoma. This novel agent targets a certain tumor-specific protein, which triggers a cascade of events that induces cancer cell death.

Cyclic pentapeptide
vascular-targeting agent
ADH-1
Adherex Technologies

The US FDA granted orphan drug designation in February 2008 to this molecularly-targeted therapy. The designation was granted for concomitant use with melphalan (alkylating agent) for the treatment of Stage IIB/C to Stage IV melanoma. ADH-1 selectively targets N-cadherin, which is frequently overexpressed in malignant neoplasms; it also promotes apoptosis and inhibits tumor angiogenesis.

Certolizumab pegol
Cimzia^®
UCB S.A.

The US FDA approved this PEGylated anti-TNFá biologic therapy in April 2008 for the treatment of Crohn?s disease. This antibody is indicated for adults with moderate-to-severe disease who are inadequate responders to conventional therapies. The development of other indications for this drug include rheumatoid arthritis and psoriasis.

A recently published study conducted by Smith, et al.*, looked at combination therapy with acitretin and biologic agents for the treatment of moderate-to-severe psoriasis. Successful management of recalcitrant disease often necessitates the amalgam of several therapeutic approaches. A vast body of clinical evidence exists for the use of acitretin in the treatment of psoriasis, and the same can be said for the mounting data on biologic therapies, however, limited data is available on their combined use. The investigators performed chart reviews on 15 psoriasis patients who received concomitant treatment with a biologic agent and acitretin. Management, side-effects, and abnormal laboratory results during combination treatment were assessed. Study findings showed that clearance of psoriasis was achieved by 29% of patients, 90% improvement by 43%, 75% improvement by 14%, and no change by 7.1%. While receiving treatment with acitretin and a biologic agent, 5 patients did not require adjunct therapy. Cessation of narrow-band ultraviolet-B (UV-B) therapy was achieved by 3 patients after receiving combination therapy for an average of 2.33 months; 1 patient continued to require phototherapy (UV-B) in addition to the biologic therapy. While on combination treatment, 3 patients developed squamous cell carcinoma (SCC); however, all 3 patients had a prior history of SCC. After 3 years of etanercept and acitretin treatment, 1 patient developed non-Hodgkin?s lymphoma, which prompted discontinuation of the biologic agent. Combination therapy with systemic retinoids and biologics may potentially provide an additional therapeutic option in the management of refractory psoriasis. Further investigations are warranted to establish the extended safety and efficacy of this integrated approach.

*Smith EC, et al. Int J Dermatol 47(5):514-8 (2008 May). 17).

The US FDA issued a black box warning in March 2008 for etanercept (Enbrel®, Immunex Corp./Amgen/ Wyeth Pharmaceuticals) concerning the risk for tuberculosis (TB) and other infections. The new prescribing information replaces a bold-face warning and calls for vigilance in patient screening and monitoring for those with active disease or those who have previously tested negative for latent TB infection. Contents of the box warning includes a statement that reactivation and new cases of TB have been observed in patients being treated with tumor necrosis factor (TNF) blocking agents; however, studies have indicated a lower risk with etanercept than with other TNF receptor antagonists. Worldwide clinical trials involving 20,000 patients treated with etanercept reported the risk for TB to be 0.01%; studies in the US and Canada with over 15,000 patients reported a risk factor of 0.007%. Post-marketing surveillance continues through open-label studies. The complete box warning information may be found at: http://www.amgen.com/pdfs/misc/enbrel_ healthcare_professionals_letter.pdf and http://www.fda.gov/medwatch/safety/2008/safety08.htm#Enbrel.