T-1249 is a fusion inhibitor developed by the same company that has already developed T-20, a small biotech company called Trimeris. The company is working in partnership with Roche to develop both compounds, and data on T-1249 has been awaited with interest because test tube studies suggest that it will be active against virus that is resistant to T-20.
Roy Gulick of Cornell Medical Centre reported on a phase I/II dose ranging study of T-1249 in heavily treatment –experienced patients. Individuals had viral load above 5,000 copies/ml after two weeks off antiretroviral therapy, and received subcutaneous injections of 6.25mg/day to 200mg/day for 14 days.
This study was a dose ranging study intended to identify a safe and effective dose to take forward into further studies, and started with 6.25mg twice daily
Median baseline HIV RNA was 5.31 log10 and the median CD4 was 64 cells/mm3. 113 of 115 patients completed dosing. Dose-dependent decreases in HIV RNA were observed. The median maximum change from baseline ranged from -0.29 (6.25 mg/day) to -1.96 (200 mg/day) log copies/ml, and the maximum CD4 cell increase was 70 cells/mm3 at a dose of 150mg once daily.
Pharmacokinetic measurements at day 7 support once daily dosing. At the highest dose (200mg once daily) patients were required to undergo four subcutaneous injections, since T-1249 is currently delivered in multiples of 50mg.
Injection site reactions were reported in 57% of patients, and became more frequent in patients who received doses above 50mg.
Other reported adverse events were headache (14%), fever (14%), lymphadenopathy (10%), candidiasis (10%) and diarrhoea (9%). It is unclear if these effects are drug related. One hypersensitivity reaction, one fever associated with an injection site reaction and one case of neutropenia were thought to be drug-related.
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References
Gulick R et al. Complete analysis of T-1249-101: safety, pharmacokinetics and antiviral activity of T-1249, a peptide inhibitor of HIV membrane fusion. 42nd ICAAC, San Diego, abstract H-1075, 2002.