Joint Meeting of the
Dermatologic and Ophthalmic Drugs
Advisory Committee (DODAC)
and the
Drug Safety and Risk Management
Advisory Committee (DSaRM)
ACS Conference Room,
Questions
1. Based on the information from the clinical
studies conducted for tazarotene capsules, is there an adequate demonstration
of effectiveness for moderate to severe psoriasis? Is there an adequate demonstration of
efficacy for “very severe” psoriasis?
2. Has the safety profile for this product been
adequately assessed?
A)
Please
provide discussion of the clinical and preclinical safety data, including
comments on bone and liver abnormalities, hyperlipidemia, and teratogenicity.
B)
Please
discuss any potential issues, regarding long term safety of oral tazarotene
with repeated use.
3. Given the safety
and efficacy information, does the Committee find a favorable balance of risks
and benefits which would support approval of this product?
4. Allergan has
submitted a risk minimization proposal to the NDA that is similar to the
isotretinoin SMART program. In addition,
they have described in their package to the advisory committee a registry
program that appears to be similar to the emerging isotretinoin risk
minimization program. Both programs
exempt males and females not of childbearing potential from many program
requirements, including refill restrictions.
A)
Please
comment on which teratogenic risk management program is preferred for
tazarotene?
B)
Please
comment on the advantages and disadvantages of having teratogenicity program
requirements applied solely for Female Child Bearing Potential.
C)
Are
the scientific and clinical uncertainties surrounding semen levels of
tazarotenic acid a factor to be considered in tazarotene risk
minimization?
5.) How can FDA best address the potential
clinical relevance of high tazarotenic acid levels in semen? Options might include:
A)
further
delineation of the potential risks (via consultation with teratogenicity
experts, additional preclinical studies, etc.)
B)
informing
clinicians and patients of the finding and its uncertain clinical relevance
C)
recommending
precautions (such as the use of condoms) pending characterization of the
potential risk
Please
comment on whether further risk assessment should be done and whether any
cautionary language or recommendations should be made while additional risk
assessment is pending.
6.) What additional
studies are needed? Are these studies
needed before or after approval of the product?