FOOD AND DRUG ADMINISTRATION
Center for Drug Evaluation and Research
ANTIVIRAL DRUGS ADVISORY COMMITTEE (AVAC) MEETING
QUESTIONS TO THE COMMITTEE
May 14, 2003
Holiday Inn, Two Montgomery Village Avenue, Gaithersburg, MD
sNDA 20-550/S-019, Valtrex® (valacyclovir hydrochloride) Caplets, GlaxoSmithKline, proposed for reduction of the risk of transmission of genital herpes with the use of suppressive therapy
Does the information presented by the applicant support the use of valacyclovir to reduce the risk of transmission of genital herpes among monogamous heterosexual couples?
If the answer to question #1 is yes, please address the following questions.
If the answer to question #1 is no, then what additional studies should be conducted?
Does the information presented support the use of valacyclovir to reduce the risk of transmission of genital herpes among populations other than monogamous heterosexual couples?
In study HS2AB3009, over 4,000 couples were screened, but only 1,498 were enrolled. A large number of couples were excluded because "susceptible" partners were found to be HSV-2 positive without clinical symptoms. Please discuss the implications of screening susceptible partners for HSV prior to initiating therapy of the source partner with valacyclovir.
In your opinion, will marketing of valacyclovir for reduction of genital herpes transmission have an impact on use of condoms and abstinence from sex during clinical HSV-2 outbreaks?
Although patients in the registrational trial were treated for eight months, valacyclovir for suppression of transmission of genital herpes will likely be used for significantly longer periods of time. What additional studies would you suggest to evaluate the potential for longer-term adverse events, including development of resistance to valacyclovir?
The primary endpoint in HS2AB3009 was the proportion of couples with clinical evidence of a first episode of genital HSV-2 in the susceptible partner. Would you recommend that primary endpoint in future studies with agents to prevent transmission of HSV-2? If not, what primary endpoint would you recommend?