LB-6. Primary Efficacy Endpoint and Safety Results of Ibalizumab (IBA) in a Phase 3 Study of Heavily Treatment-Experienced Patients with Multi-Drug Resistant (MDR) HIV-1 Infection
Session: Oral Abstract Session: Late Breaker Oral Abstracts
Saturday, October 29, 2016: 11:20 AM
Room: 283-285
Background: Despite success of combination antiretroviral (ARV) therapy, some patients fail to achieve durable viral suppression due to multi-drug resistant (MDR) HIV. Ibalizumab (IBA) is the first long-acting monoclonal antibody HIV-1 entry inhibitor in Phase 3 development for treatment of MDR HIV. IBA was granted Orphan Drug status and Breakthrough Therapy designation by the FDA.

Method:  TMB-301 is an on-going single arm, 24-week (wk) study of IBA plus optimized background regimen (OBR) in treatment experienced patients with MDR HIV-1. The primary objective was to demonstrate antiviral activity at DAY 14 (7 days after IBA initiation). Patients were monitored for 7 days on a failing ARV regimen (control period). On DAY 7 a 2000mg IBA loading dose was administered intravenously (IV) as functional monotherapy. The primary efficacy endpoint was the proportion of patients achieving a ≥ 0.5 log10decrease in HIV-1 RNA from DAY 7/Baseline (BL) to DAY 14. An OBR with at least one sensitive agent was initiated on DAY 14. IBA was continued at 800mg IV every two wks for 24 wks on study treatment. Safety and additional efficacy endpoints were evaluated.

Result: Forty heavily treatment-experienced patients with MDR HIV were enrolled, mean age of 51 years, 15% female, and 45% non-white. Mean duration of HIV infection was 21 years and 28% were treated with ≥10 previous ARVs. Mean BL CD4+ T cell count was 161 cells/µL (50% <100 cells/µL) and mean BL viral load (VL) was 5.0 log10 (18% BL VL ≥100,000 copies/mL). 35% of patients required an investigational agent in OBR due to extensive resistance. 83% achieved ≥ 0.5 log10decrease from BL to DAY 14 on IBA versus 3% during the control period. No treatment-related SAEs or discontinuations were reported during DAY 0-14. End-of-study safety and efficacy assessments are ongoing.

 TABLE 1. Day 14 Intent-to-Treat Results (IBA added to stable failing regimen)

Endpoint

Control*

IBA

p-value

≥ 0.5 log10 decrease from BL, n (%)

1 (3)

33 (83)

<0.0001

≥ 1.0 log10 decrease from BL, n (%)

0 (0)

17 (55)

<0.0001

*Protocol deviations affecting analysis: incomplete Day 0 results (n=1, excluded) and OBR started during control period (n=1, included)

Conclusion: IBA demonstrated statistically significant VL reductions compared to control in MDR HIV patients when added to a failing regimen and was well tolerated.

Jacob Lalezari, MD1, W Jeffery Fessel, MD2, Shannon Schrader, MD3, Princy Kumar, M.D.4, Gary Richmond, MD5, Christian Marsolais, PhD6, Steven Weinheimer, PhD7 and Stanley Lewis, MD7, (1)Quest Clinical Research, San Francisco, CA, (2)Kaiser Foundation Research Insitute, San Francisco, CA, (3)Research Access Network, Houston, TX, (4)Division of Infectious Diseases and Travel Medicine, Medstar Georgetown University Hospital, Washington, DC, (5)Broward Gen. Med. Ctr, Ft. Lauderdale, FL, (6)Medical Affairs, Theratechnologies Inc., Montreal, QC, Canada, (7)TaiMed Biologics USA, Irvine, CA

Disclosures:

J. Lalezari, TaiMed Biologics USA: Investigator , Research support

W. J. Fessel, TaiMed Biologics USA: Investigator , Research support

S. Schrader, TaiMed Biologics USA: Investigator , Research support

P. Kumar, TaiMed Biologics USA: Investigator , Research support

G. Richmond, TaiMed Biologics USA: Investigator , Research support

C. Marsolais, Theratechnologies Inc: Employee , Salary

S. Weinheimer, TaiMed Biologics USA: Employee , Salary

S. Lewis, TaiMed Biologics USA: Employee , Salary

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.