July 12, 2002
T-20 is a fusion inhibitor that almost certainly will be approved by the FDA and the European and Australian regulatory agencies by next winter. Enfuvirtide is the name selected for T-20. It is so difficult to pronounce that I am sure this drug will always be known as T-20.
These are the two pivotal trials that will be used to obtain this approval. The design of both studies is very similar: in both TORO 1 and TORO 2, highly experienced patients were randomized to receive open label T-20 (90 mg SC q 12h) or not, in addition to an optimized background regimen. Patients had to have previous experience with all classes of drugs and more than 5,000 copies of HIV RNA per ml.
This was a very short and crisp presentation given in tandem by Keith Henry on behalf of the American investigators and Bonaventura Clotet on behalf of the European ones.
Four hundred ninety-one patients were enrolled in TORO 1 (the American study). Baseline, patients had received a median of 12 antiretrovirals, for a total of seven years, and AIDS events were very frequent (87 percent). Median viral load was 5.2 logs and median CD4+ was 80. The bottom line: this was an extremely advanced and resistant population. Three hundred twenty-six patients were randomized to the T-20 arm and 165 to the optimized arm. In the T-20 arm, there was a decrease of -1.70 logs of HIV RNA vs. -0.76 logs in the control arm. Injection reactions were common, but led to discontinuation of T-20 in only 0.8 percent of the patients. Fifty-two percent of the patients had more than a one-log decay and, after 24 weeks, 37 percent of the patients had a viral load of less than 400 vs. 16 percent in the control group. Not unexpectedly, CD4+ count increased more in the T-20 group.
Five hundred four patients enrolled in TORO 2 (335 in the T-20 arm and 169 in the control arm). The demographic and previous antiretroviral experience was similar to the previously discussed numbers in TORO 1. Only 3 percent of the patients quit because of skin site reactions. At 24 weeks, patients in the T-20 arm experienced a -1.43 log viral load decay vs. 0.65 in the placebo arm. The CD4+ responses were also better. One log reduction occurred in 43 percent of the patients taking T-20 and, at 24 weeks, 28 percent of the patients had their viral load become undetectable.
The results of both trials are very supportive for T-20, and, unless some weird thing happens, this drug will certainly be approved.
However, T-20 will face two problems in its widespread use as an antiretroviral agent. The first is that it must be used subcutaneously, and that can be problematic for some individuals -- although we should not forget that we have successfully used drugs like insulin that also have to be given subcutaneously. Second, the long-term tolerability might be an issue beyond 24 weeks, but we did not hear about this during the presentation. In conclusion, it looks like T-20 will be a nice addition to our armamentarium.