T-1249, the new fusion inhibitor being developed by Trimeris and Roche, is active in patients who have greatly reduced susceptibility to T-20 (enfuvirtide), according to an interim analysis of the phase I/II efficacy study presented today at the Tenth Conference on Retroviruses and Opportunistic Infections in Boston.
This means that if T-1249 continues to prove safe and shows durable efficacy, it could provide a second-line fusion inhibitor option for patients with extensive HIV treatment experience.
The T-1249-102 study recruited patients in the United States who had detectable viral load above 5,000 copies/ml and who had received T-20 in the TORO 1 study or the phase II T-20 study. So far, 25 patients have completed the first ten days of T-1249 treatment, and results from these patients were presented at the meeting.
Baseline genotype data were available for 24 patients, and showed that all had genotypic resistance to T-20. Phenotypic resistance data were available for 15 patients, and showed an average 77-fold reduction in T-20 susceptibility. Participants had been exposed to a failing T-20-containing regimen for a median of 59 weeks, and had a median baseline viral load of 100,000 copies (5.0 log).
T-1249 was dosed as a subcutaneous injection, either 192 mg once daily or 96 mg twice daily, according to patient choice.
After ten days of T-1249 treatment, the mean viral load reduction was –1.13 log, and 63% of patients had experienced a viral load reduction greater than 1 log by day 11. This was associated with a shorter exposure to a failing T-20-containing regimen. Patients with less than 48 weeks on T-20 after viral failure had an average viral load reduction of -1.6 log copies/ml, compared to an average reduction of 0.94 log copies/ml in those with greater than 48 weeks on a failing T-20 containing regimen.
No serious adverse events appeared to be associated with T-1249 treatment. One self-limiting allergic reaction characterised by grade 2 rash appeared on day 11 after dosing was completed, whilst possible laboratory toxicities were confined to liver enzyme elevations (ALT and AST) in one patient and creatinine, calcium and glucose elevations in a seriously ill patient who subsequently died of multi-organ failure very shortly after the conclusion of the dosing period. The death is not considered to be connected to T-1249 treatment.
Larger phase II studies are now planned, and a new formulation which can be dosed as 100mg once daily will be used in these studies.
Further information on this website
Miralles GD et al. T-1249 demonstrates potent antiviral activity over 10 day dosing in most patients who have failed a regimen containing enfuvirtide (ENF): planned interim analysis of T-1249-102, a phase I/II study. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 14lb, 2003.