572: Der neue Integrasehemmer auch bei Therapienaiven in Phase 2 erfolgreich (TH LB B205)
Wir haben über die Viking-Studie berichtet: Der neue Integrase-Hemmer von GSK wurde bei Patienten mit Raltegravir-Resistenz eingesetzt. in einem Late-Braker wurden bereits die ersten unverblindeten Woche 16Resultate einer Studie bei zuvor unbehandelten Patienten vorgestellt. Die Daten lassen gute Wirksamkeit erahnen. Drei Dosierungsarme (10-50mg) wurden mit Efavirenz (plus Kivexa oder Truvada) verglichen. Natürlich ist es möglich, dass Efavirenz bis zur Woche 24 noch einiges aufholen wird, was wir von Raltegravir kennen. Doch die Resultate waren auch in Bezug auf das Nebenwirkungsspektrum und auf die Entwicklung von Resistenzen sehr positiv. Die Substanz geht nun in Phase 3, gewählt wurde die 50mg Dosierung.
Once-daily S/GSK1349572 as part of combination therapy in antiretroviral naïve adults: rapid and potent antiviral responses in the interim 16-week analysis from SPRING-1 (ING112276)
J. Arribas1, A. Lazzarin2, F. Raffi3, A. Rakhmanova4, G. Richmond5, J. Rockstroh6, J. van Lunzen7, B. Young8,9, S. Almond10, C. Brothers11, S. Min11, G. Nichols11
Background: S/GSK1349572, a next-generation HIV-1 integrase inhibitor, demonstrated potent antiviral activity in Phase2a with once-daily, unboosted dosing.
Methods: SPRING-1 is a Phase 2b, multicentre, partially-blinded dose-ranging study in therapy-naïve adults, randomized 1:1:1:1 to 10mg, 25mg or 50mg of S/GSK1349572 or efavirenz(EFV) 600mg once-daily with either co-formulated TDF/FTC or ABC/3TC.
Results: 205 subjects received study drug: 86% male, 20% non-white, 26%>100,000c/mL HIV-1 RNA, 67% TDF/FTC. Plasma HIV-1 RNA declined rapidly across all S/GSK1349572 doses with no differences in gender or NRTI subgroups. Time to HIV RNA < 50c/mL was shorter in S/GSK13249572 arms than the EFV arm (each p< 0.001 vs. EFV; log-rank test); by Week 4, 66% of S/GSK1349572 subjects were suppressed vs. 18% on EFV. Two protocol-defined virologic failures occurred, one EFV (< 1log10 decline by Week 4), and one S/GSK1349572 (Week 4 rebound with only M184V mutation detected). Most AEs on S/GSK1349572 were grade 1. More drug-related AEs of moderate-or-higher intensity were reported on EFV (18%) than S/GSK1349572 (6%) arms; none occurred in more than one S/GSK1349572 subject. No SAE was considered related to S/GSK1349572. Five subjects (1:S/GSK1349572 and 4:EFV) withdrew due to AEs. Mean change from baseline in LDL cholesterol was lower amongst S/GSK1349572 subjects (+0.066mmol/L) than EFV subjects (+0.436mmol/L).
| S/GSK1349572 10mg (n=53) | S/GSK1349572 25mg (n=51) | S/GSK1349572 50mg (n=51) | EFV control (n=50) | |
|
Mean baseline HIV-1 RNA (log10 c/mL) |
4.42 | 4.38 | 4.58 | 4.46 |
| Mean change from baseline HIV-1 RNA at 2 weeks (log10 c/mL) | -2.39 | -2.37 | -2.40 | -1.93 |
| %<50c/mL at 16 wks (by TLOVR) | 96% (51/53) | 92% (47/51) | 90% (46/51) | 60% (30/50) |
| Median baseline (change from baseline at 16 weeks) CD4+ cells/mm3 | 289 (+153) | 330 (+176) | 305 (+160) | 308 (+115) |
[Planned Week 16 Interim Analysis Results]
Conclusions: S/GSK1349572 administered once-daily without a PK booster was very well tolerated with potent antiviral activity at all doses explored in SPRING-1. Time to undetectable viral load was significantly shorter in the S/GSK1349572 arms. All subjects continue on blinded S/GSK1349572. These data fully support progression of S/GSK1349572 into Phase 3 evaluation.
Links:
- Nichols, et.al.-TBLBB205
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- Präsentation (.ppt) nur unter Slides mit Audio vorhanden
