phase 2 of new arvs bms-955176 (maturation inhibitor) - ai468002 study
TRANSCRIPT
Phase 2 of new ARVsBMS-955176 (maturation inhibitor)
- AI468002 Study
AI468002 Study: BMS-955176 Phase II
BMS-1765 mg qd
or placebo
BMS-17610 mg qd
or placebo
BMS-17620 mg qd
or placebo
BMS-17640 mg qd
or placebo
BMS-17680 mg qd
or placebo
Design
– Phase IIa, randomised, double-blind, dose-escalating study– ARV-naïve (≤ 1 week of treatment) or experienced (PI and maturation
inhibitor naïve) patients, > 18 years, HIV RNA > 5,000 c/mL, CD4 cell count > 200/mm3
– For all dose groups : 8 patients on BMS-176 qd and 2 on placebo– HIV RNA evaluated at Day 1 to 14, Day 17-19 and Day 24
AI468002 Study Hwang C. CROI 2015, Abs. 114LB
BMS-176120 mg qdor placebo
PlaceboN = 12
BMS-1765 mgN = 8
BMS-17610 mgN = 8
BMS-17620 mgN = 8
BMS-17640 mgN = 8
BMS-17680 mgN = 8
BMS-176120 mg
N = 8
Median age, years 36 43.5 39 33 38 31.5 37.5
Female 0 0 12.5% 0 0 0 0
HIV RNA (log10
c/mL), median4.0 4.1 4.0 3.6 4.0 3.8 3.8
CD4 cell count/mm3, median 458 437 539 512 536 504 498
Baseline characteristics
ARV-naïve : 92% ; ARV-experienced : 8%
AI468002 Study: BMS-955176 Phase II
AI468002 Study Hwang C. CROI 2015, Abs. 114LB
Maximum median reduction in HIV RNA from baseline, log10 c/mL PlaceboN = 12
5 mg qdN = 8
10 mg qdN = 8
20 mg qdN = 8
0.0
-0.2
-0.4
-0.6
-0.8
40 mg qdN = 8
80 mg qdN = 8
120 mg qdN = 8
-1.2
-1.4
-1.6
-1.8
-1.0- 0.381
- 0.498 - 0.976 - 1.115
- 1.555 - 1.654- 1.701
• Median change in HIV RNA from baseline to day 11 was – 1.4 log10 c/mL• BMS-955176 exposure-response relationship is consistent with dose-
response antiviral activity
AI468002 Study: BMS-955176 Phase II
AI468002 Study Hwang C. CROI 2015, Abs. 114LB
Maximum median reduction in HIV RNA, log10 c/mLby baseline Gag polymorphisms
PlaceboN = 12
5 mg qdN = 8
10 mg qdN = 8
20 mg qdN = 8
0.0
-0.2
-0.4
-0.6
-0.8
40 mg qdN = 8
80 mg qdN = 8
120 mg qdN = 8
-1.2
-1.4
-1.6
-1.8
-1.0
-0.55
-0.48
-1.05 - 1.66- 1.55 - 1.57- 1.75
-0.33 -0.52 -0.97- 0.93
- 1.43 - 1.98- 1.71
6 5 3 5 3 5 3 4 4 3 6 2 5 3
-2.0No polymorphisms
With polymorphisms(V362, Q369, V370)
AI468002 Study: BMS-955176 Phase II
AI468002 Study Hwang C. CROI 2015, Abs. 114LB
PlaceboN = 12
BMS-1765 mgN = 8
BMS-17610 mgN = 8
BMS-17620 mgN = 8
BMS-17640 mgN = 8
BMS-17680 mgN = 8
BMS-176120 mg
N = 8
Discontinuation due to adverse event 0 0 0 0 0 0 0
Serious AEs 0 0 0 0 0 0 0
Grade 3-4 related AEs 0 0 0 0 0 0 0
Death 0 0 0 0 0 0 0
Laboratory abnormalities (Grade 2-4)
0 0 0 0 0 1* 0
Adverse events
* Transient grade 3 neutropenia reported as related to study drug
AI468002 Study: BMS-955176 Phase II
AI468002 Study Hwang C. CROI 2015, Abs. 114LB
Conclusion
– BMS-955176 is a potent, once-daily, second-generation maturation inhibitor with a maximum median decrease of 1.7 log10 copies/mL in plasma HIV RNA with 10 days of monotherapy at the 40 mg dose
• Doses of 20-120 mg qd resulted in decreases > 1 log10 c/mL
• Plateau of ≈ - 1.6 log10 c/ml at 40-120 mg qd
– Similar antiviral activity against both wild-type HIV-1 and HIV-1 with Gag polymorphisms not responsive to a first-generation maturation inhibitor
– Well tolerated • No serious adverse events, • No adverse events leading to discontinuation, • No grade 3-4 adverse events,• No significant laboratory abnormalities
AI468002 Study: BMS-955176 Phase II
AI468002 Study Hwang C. CROI 2015, Abs. 114LB