Delegates at the 8th Retroviruses Conference currently underway in Chicago have heard new data this morning on T-1249, a fusion inhibitor. Interest in this new class of antiretrovirals, has so far focussed on T-20 (pentafuside), which has been studied in drug-experienced individuals. At present, drugs in this class are administered by subcutaneous injection, a method which does not favour its use beyond the ‘salvage’ setting.
T-1249 is a second generation fusion inhibitor, which like T-20, is under development from Trimeris with Roche Products. Findings from study T-1249-101, the first study to administer this drug to humans, were presented this morning.
72 people were recruited to this dose-ranging, monotherapy pilot study. All were treatment experienced with viral load over 5,000 copies. Following a two week antiretroviral wash-out period, volunteers were randomised to one of six dosing arms: 6.25mg once or twice daily; 12.5 mg once or twice daily; or 25mg once or twice daily.
Of 72 individuals enrolled, 63 received at least one dose, and 61 completed the 14 day study period. Mean viral load was in the range of 4.95-5.54 log, mean CD4 from 84-146 cells, and the prior number of antiretrovirals which participants had been exposed to was 10. Of 194 treated-related adverse events, just two were considered serious: one case of hypersensitivity and one neutropenia. Aside from these, common side-effects were injection site reactions (40%); headache (11%); dizziness (8%); fever (8%); and diarrhoea (6%).
Viral load responses, and average trough concentrations were dose dependent, though at the 6.25mg dose there was no measurable virological effect. At the other end of the spectrum, those who received the twice daily high dose exhibited an average viral load fall of 1.3 logs between 10 and 14 days after treatment begun.
T-1249 is a so-called ‘rationally designed’ compound, meaning its structure is intended to allow efficacy against HIV mutants which are resistant to T-20; and indeed test tube studies support this possibility. An alternative proposed by a delegate here in Chicago would be for Trimeris/Roche to investigate the combined use of T-20 and T-1249, given the shortage of new drug options with activity against multiply resistant virus.
Eron J et al. A 14-day assessment of the safety, pharmacokinetics, and antiviral activity of T-1249, a peptide inhibitor of membrane fusion. 8th Conference on Retroviruses and Opportunistic Infections, abstract 14, Chicago, February 4-8th, 2001.