• Enfuvirtide (T-20) in Combination With an Optimized Background (OB) Regimen vs. OB Alone in Patients With Prior Experience or Resistance to Each of the Three Classes of Approved Antiretrovirals (ARVs) in Europe and Australia (LbOr19A)
  Authored by B. Clotet, A. Lazzarin, D. Cooper, J. Reynes, K. Arasteh, M. Nelson, C. Katlama, J. Chung, L. Fang, J. Delehanty, M. Salgo
  View the original abstract
• Enfuvirtide (T-20) in Combination With an Optimized Background (OB) Regimen vs. OB Alone in Patients With Prior Experience or Resistance to Each of the Three Classes of Approved Antiretrovirals (ARVs) in North America and Brazil (LbOr19B)
  Authored by K. Henry, J. Lalezari, M. O'Hearn, B. Trottier, J. Montaner, P. Piliero, S. Walmsley, J. Chung, L. Fang, J. Delehanty, M. Salgo
  View the original abstract

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.