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TMC-114 48 Week Study Results: lipids, potency, safety
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Reported by Jules Levin
XVI Intl AIDS Conference, Toronto Aug 15, 2006
I just returned from the posters and before that hearing Clinton speak and just before that the oral session on ARTs where the 48-week TMC study results were reported. There are numerous posters here on TMC114 and TMC125 including 48 weeks TMC125 and response by number of NNRTI mutations. Thursday is the only oral ART session left and the biggest, actually it's a bit of a joke as 18 orals will be presented and 7 minutes are allotted for each talk; this is where the 24 week integrase study results in treatment-naives will be presented. The MK-0518 Merck integrase and TMC114 are the 2 new drugs highlighted as this meeting, as well an Expanded Access Program will open soon for the NNRTI TMC125 and later on for Maraviroc the new CCR5 inhibitor. Clinton was magnetic and inspiring. There must have been 5000 or maybe 10,000 people in the room to hear him speak. I think his presidency was preparation for this job. He has done a great job on international AIDS. He was inspirational because he shows you what one person can do not just regarding HIV but for anything if you set your mind to it. Following here the 48 week TMC114 study results reported this morning.
"TMC114/r provides durable viral load suppression in treatment-experienced patients: POWER 1 and 2 combined Week 48 analysis"
Sharon Walmsley from Canada reported the study results.
XVI Intl AIDS Conference, Toronto, Aug 2006
Lazzarin A, Queiroz-Telles F, Frank I, Rockstroh J, Walmsley S, De Paepe E, Vangeneugden T, Spinosa-Guzman S and Lefebvre E
Lazzarin A, et al. XVI IAC 2006. Abstract TUAB0104
SUMMARY. 61% of patients receiving TMC114 plus optimized back ground therapy achieved a 1 log or more reduction in viral load at 48 weeks on therapy, and 46% achieved <50 copies/ml in viral load. CD4s increased an average of 102 for the patients on TMC114. The 48 week study results did not reveal new safety findings and appears to confirm that TMC114 is generally well tolerated as compared to earlier data at week 24. Treatment exposure was greater for the TMC114 group (157 patient years) than the patients not receiving TMC114 (75 years). The majority of adverse events were grade 1-2, discontinuations were infrequent. Most of the safety outcomes were comparable to patients not receiving TMC114. Diarrhea was the most frequent adverse events for patients receiving TMC114: 20% vs 28% for patients not receiving TMC114. Overall, 20% of TMC114 patients and 14% not receiving TMC114 reported at least 1 serious adverse event. Individual serious adverse events were reported in no more than one TMC114 patients (<1%), except for pneumonia and acute renal failure (two patients each). Discontinuations due to adverse events were infrequent (9% for TMC114 vs 5% for patients not receiving TMC114. At the Tibotec symposium early this morning they reported the patient groups taking TMC114 who benefited from Fuzeon and showed data that tipranavir might be effective for patients who fail TMC114 (see data following the oral presentation for the TMC114 study).
POWER 1 and 2: pivotal phase IIb trials
- Two randomized, controlled, partially blinded, multicenter, phase IIb trials with the same study design and objectives
POWER 1 (TMC114-C213)1,2
POWER 2 (TMC114-C202)3,4
- Objectives
- compare antiretroviral efficacy and safety of different TMC114 (darunavir)/r doses with that of investigator-selected control protease inhibitor(s) (CPI[s]) in treatment-experienced patients
- Primary endpoint
- confirmed response (ITT-TLOVR) defined as ≥1.0 log10 HIV-1 RNA reduction from baseline (BL) at 48 weeks (the time of analysis)
ITT = intent to treat;
TLOVR = time to loss of
virologic response
1. Katlama C, et al. 3rd IAS 2005. Abstract WeOaLB0102
2. Grinsztejn B, et al. 3rd IAS 2005. Abstract WePeLB6.201
3. Wilkin T, et al. 45th ICAAC 2005. Abstract 2860
4. Berger D, et al. 45th ICAAC 2005. Abstract H-1094
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