FTC (Emtriva[TM]) approved.

The U.S. FDA announced the approval of FTC (brand name Emtriva, generic name emtricitabine, former brand name Coviracil[TM]) on July 2, 2003.

FTC is chemically related to 3TC. It was approved primarily on the basis of two clinical trials: one comparing FTC with d4T, and the other comparing it with 3TC. FTC is taken once per day with or without food. Special dosing is needed for patients with kidney problems.

Shortly before approval, a clinical trial comparing FTC and d4T was stopped early by its Data Safety Monitoring Board (a somewhat unusual occurrence) because the patients in that trial who were randomly assigned to FTC were clearly doing better than those randomly assigned to d4T. (Note that all patients in this trial were also taking ddI [Videx[R]] and efavirenz [Sustiva[R]]; combining d4T and ddI is no longer recommended because of side effects, a problem that probably contributed to the superiority of FTC in this study.)

European approval is likely by late 2003.

FTC was approved mainly on the basis of two trials: the comparison with d4T above, and a trial in which patients who were on treatment including 3TC were randomly assigned to either stay on their current regimen or switch the 3TC to FTC. The patients in both groups did comparably well. Four percent of those on FTC discontinued it due to adverse events, vs. none who stayed on 3TC--but this difference is hard to interpret since those who could not tolerate 3TC would have stopped that treatment earlier and could never have entered this particular trial.

FTC has had a long development history involving several companies, but now will be marketed worldwide by Gilead Sciences, Inc. (The drug has been shown to be active against HIV clades A, C, D, E, F, and G,--as well as against clade B, which causes almost all AIDS cases in the U.S.) In the U.S., Gilead announced that the "wholesaler acquisition cost" is $252.83 for a bottle of 30 capsules, a one-month supply.

The FDA's announcement noted that FTC has only been approved for adults age 18 and over, as pediatric safety and effectiveness have not been established. It suggested using resistance testing with pre-treated patients to check that their virus is likely to be susceptible to FTC (the mutations M184V or M184I are the most common cause of viral resistance to FTC). It noted that about 1% of patients in clinical studies overall have discontinued FTC due to adverse events. It also recommended that all patients be tested for the presence of chronic hepatitis B virus before starting antiretroviral treatment for HIV, and that patients co-infected with hepatitis B be closely monitored for at least several months after FTC is discontinued, as there have been hepatitis B flare-ups when treatment is stopped. As with all members of this drug class (nucleoside reverse transcriptase inhibitors), the prescribing information carries a black-box warning about risk of lactic acidosis and liver toxicity.

The new HIV treatment guidelines (see article in this issue) did not consider FTC, because it was approved after the guidelines had been developed. FTC will be discussed in the next version.

Comment

As with any new drug, FTC's place in clinical practice will develop over time. This antiretroviral may have important advantages, but other treatments are much better known. Our guess is that many physicians will be conservative at first, but will use FTC as more is learned about long-term safety and effectiveness, and about which patients are most likely to benefit.