Tibotec announces expanded access programme for new NNRTI TMC125

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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.

Glossary

treatment-experienced

A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. This method provides a better estimate of the real-world effect of a treatment than an ‘on treatment’ analysis.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

phase II

The second stage in the clinical evaluation of a new drug or intervention, in which preliminary data on effectiveness and additional information about safety is collected among a few hundred people with the disease or condition.

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).