Update on Drugs and Drug News – April 2008

The US FDA accepted for review a supplemental Biologics License Application in January 2008 for this recombinant alfa interferon, and has granted Priority Review status for the adjuvant treatment of patients with Stage III malignant melanoma.

The US FDA granted orphan drug designation in January 2008 to this novel small molecule. By elevating oxidative stress levels, the agent triggers apoptosis by sensitizing cancer cells to agents that induce cell death through the mitochondrial pathway. In combination with paclitaxel, it is presently in Phase III clinical trials for the treatment of metastatic melanoma.

The US FDA approved this dermal filler in March 2008 for the reduction of moderate-to-severe facial lines, folds, and wrinkles. A controlled clinical study showed that the addition of lidocaine significantly relieved injection site pain.

The rise of cutaneous melanoma (CM) has been steadily recorded by cancer registries over the past several decades. Although the causal relationship with other forms of skin cancer can be traced to exposure to levels of ultraviolet radiation, in CM, this distinct relationship cannot be established. Genetic influences appear to represent the best indicator in assessment of risk. In addition, photochemotherapy with 8-methoxypsoralen combined with ultraviolet-A radiation (PUVA), which is used to treat psoriasis and vitiligo, has also been found to be a potentiating factor. Psoralens, a form of furocoumarins, occur naturally in botanical sources that include vegetables and fruits (of particular interest is the citrus variety), and are known to exert photocarcinogenic effects that induce DNA damage. Under normal dietary conditions, exposure levels do not spawn phototoxic effects. The hypothesis, offered by Sayre, et al.*, is that one of the contributing factors to the increased incidence of CM may be attributable to the elevated intake of food sources containing photocarcinogenic furocoumarins. This suggestion follows from a recent large study of nurses where a positive association was found between citrus consumption and the development of CM.

*Sayre RM, Dowdy JC. The increase in melanoma: are dietary furocoumarins responsible? Med Hypotheses 70(4):855-9 (2007 Sep 17).

The US FDA released a draft guidance to industry on “Good Reprint Practices” for the distribution of medical or scientific journal articles and reference publications that contain information regarding unapproved uses of US FDA-approved drugs and medical devices. The FDA recognizes the contribution of off-label uses of products to medicine; however, the regulatory body is compelled to also implement safeguards against the promotion of unapproved uses. Recommendations contained in the draft guidance include:

• Literature for dissemination should be published by an organization that has an editorial board.
• The publisher should provide full disclosure of any conflicts of interest or biases for all authors, contributors, and editors associated with the publication.
• Production should include a peer-review process and adhere to specific procedures outlined within this draft guidance.

Supplements or publications that are funded by manufacturers of the product described in an article, especially those where the content is unsupported by credible medical evidence, may be considered as false or misleading and the US FDA will recommend against distribution of such material. The US FDA reserves the legal authority to determine if distribution of an article or publication constitutes promotion of an unapproved “new use”, or whether such activities cause a product to be considered misbranded or adulterated under the Federal Food, Drug and Cosmetic Act. More details on this proposal can be found at: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01798.html.