While the FDA approval trials were completed over a year ago, work continues on two additional trials to determine the minimum dose to maintain efficacy.
Vancouver - Although a panel of the Food and Drug Administration (FDA) rejected an application for the approval of tazarotene (Tazorac, Allergan) for distribution of the retinoid for the treatment of psoriasis in the United States this past spring, clinical research continues with the drug and other retinoids.
Though Tazorac has been available as a topical agent for the treatment of acne and psoriasis for about five years, its systemic use as a tablet has not yet been licensed in any country.
While the FDA approval trials were completed over a year ago, work continues on two additional trials to determine the minimum dose to maintain efficacy. The concerns of the FDA committee related, in part, to the desire for Allergan to implement a more stringent pregnancy prevention program.
The potential teratogenic effects of other retinoids have led the FDA to require robust safety programs in the past.
"Look at Accutane, for example," he says. "The restrictions make it necessary for all parties to be registered and monthly pregnancy tests to be obtained and validated prior to the dispensing of medication, and that program is under constant review by an FDA subpanel.
"The concerns are prompted partially by the fact that acne is typically a disease of young adults or adolescents. Considering the potential teratogenic effects, you're looking at a population that is at very high risk."
It is difficult to compare the clinical results for Tazorac with those for other retinoids, such as Soriatane, because other drugs were approved in the early 1980s under a less stringent review process, in part because the applicable population tends to consist of older adults, Dr. Papp says.
Allergan also has found that Tazorac has clinical efficacy in the treatment of cystic acne, although those results were not submitted to the FDA. In comparison, the efficacy of most other retinoids is very specific, Dr. Papp explains.
"Soriatane is quite specifically for treating psoriasis, and it has very little effect on acne. Conversely, Accutane has very little effect on psoriasis. This gets back to the specificity of the transcription element again," Dr. Papp says.
The new basic research on retinoid receptor specificity points to a future development goal for manufacturers - designing new retinoids with improved receptor specificity.
This is especially important because retinoids have gotten a mixed review from the government over the years: the retinoid Tegason was withdrawn from market some time ago, for instance.
Nonetheless, promising research on new retinoids continues. A new retinoid called bexarotene has been available for the past three years for the treatment of specific skin leukemias and lymphomas, such as mycosis fungoides. Other applications include treatment of Bowen's disease and multiple squamous cell carcinomas.
In addition, in Switzerland, Basilea Co. is developing a retinoid for hand dermatitis, which may also be useful in certain lympho- proliferation disorders.
Dr. Papp stresses the current retinoids are essential therapeutic tools for the treatment of skin diseases.
"It is important that this entire class of medication continue to flourish," he says. "It is equally important to continue development of new retinoids to improve efficacy and safety profiles."
Disclosure: Dr. Papp is on the speakers' bureau and has been a consultant and served on advisory boards for Allergan and Roche Pharmaceuticals, as well as serving as a principal investigator.