Tibotec Pharmaceuticals announced yesterday that the expanded access programme (EAP) for TMC125, its investigational non-nucleoside reverse transcriptase (NNRTI), has opened in the U.S. and will open shortly in Canada and Europe, subject to the necessary approvals. The programme will provide access for highly treatment-experienced HIV-positive people who need the compound to construct a viable treatment regimen.
TMC125, also known as etravirine, is a next-generation NNRTI active against NNRTI-resistant strains of HIV. The phase III clinical trials (DUET 1 and 2) in treatment-experienced HIV-1 infected patients are ongoing and have recently completed enrollment. The safety and efficacy of TMC125 in combination with other antiretroviral agents have not been established, and individuals who have already applied to participate in the expanded access programme for the Merck integrase inhibitor MK-0518 will not be able to take TMC125 alongside it.
For more about the programme, visit www.clinicaltrials.gov. Healthcare professionals and people living with HIV/AIDS in the US may obtain information by calling 1-866-889-2074 or emailing TMC125EAP@i3research.com.
Currently, over 15 US sites have initiated the expanded access programme and are listed on www.clinicaltrials.gov.
European recruitment details will be announced when approval for the programme is granted in each European country.
The TMC125 EAP is available to HIV-1 infected adults, at least 18 years old, who have limited treatment options either due to virological failure or intolerance to multiple ARV regimens. Patients must be three-class experienced, having received licensed treatment from each of the three major oral classes of anti-HIV drugs (NRTIs, NNRTIs, and PIs), and must have received at least two PI-based regimens.
Tibotec presented 48-week findings on TMC125 at the Sixteenth International AIDS conference in August 2006 in Toronto. The presented data were the final analysis of study TMC125-C223, a phase IIb dose-finding, randomised, partially-blinded study in HIV-1 infected adult patients (n=199) with substantial treatment experience, documented evidence of NNRTI resistance and three or more primary PI mutations. The study compared doses of 400mg and 800mg twice daily.
After 48 weeks 23% of patients in the 400mg etravirine group and 22% of patients in the 800mg etravirine group had viral loads below 50, compared to none of the patients in the control group, who received a regimen optimised by resistance testing.
Intent to treat analysis showed that the mean change from baseline in viral load at week 48 was -0.88, -1.01 and -0.14 log10 copies/ml in the TMC125 400mg and 800 mg bid and active control groups respectively. A decrease from baseline in plasma viral load of at least 1 log was achieved by 31%, 34% and 8% of patients respectively. In these patients with NNRTI resistance, the viral load reduction was significantly greater than in the active control at 48 weeks (p=0.018 and p=0.002 respectively).