ClassName/CompanyApproval Dates and Comments
(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.

MelanomaCyclic pentapeptide
vascular-targeting agent

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

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.

Drug News

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).

FDA Warning

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:
healthcare_professionals_letter.pdf and