HIV suppression and safety with ibalizumab at 48 weeks in expanded access
18 October 2019. Related: Conference reports, Antiretrovirals, IDWeek 2019.
Nearly half of ibalizumab expanded access programme participants who received the monoclonal antibody for 48 weeks reached and maintained an undetectable viral load, despite multidrug resistance when starting ibalizumab. 
Response rates would have been higher if the analysis included seven people who left the programme to take commercially available ibalizumab. At the 24-week point, four of 24 people left the study because of adverse events and three because of virologic failure.
Ibalizumab (Trogarzo) is the first humanised monoclonal antibody licensed for treatment of multidrug-resistant HIV in combination with other antiretrovirals. The agent blocks HIV from binding to cellular CCR5 or CXCR4 coreceptors after it binds to CD4 on the cell surface. 
At week 25 of a phase 3 trial, 43% of participants reached a viral load below 50 copies/mL and 50% below 200 copies/mL. 
The IDWeek report involves highly pretreated people enrolled in the TMB-311 ibalizumab expanded-access programme. 
Everyone had a viral load above 1000 copies/mL, documented resistance to at least one antiretroviral in three classes, and full sensitivity to at least one antiretroviral that could anchor an optimised background regimen given with ibalizumab. No expanded-access participants had taken ibalizumab before.
Participants received a 2000 mg intravenous loading dose of ibalizumab and started the daily optimised background regimen at the same time. Fourteen days later, people started receiving 800 mg of ibalizumab every two weeks as the daily background regimen continued.
The 38 expanded access participants averaged 50 years in age, 87% were men, and 47% were nonwhite. The group had a median viral load of 54,050 copies/mL, and 24% had a viral load above 100,000 copies/mL. Median CD4 count stood at 26 cells/mm3, and 58% of participants had a count below 50 cells/mm3.
Most treatment-emergent adverse events were mild to moderate, the most frequent being diarrhea in nine people, headache in eight, rashes, nausea, cough, and fatigue. Immune reconstitution inflammatory syndrome (IRIS) developed in one person who had to stop ibalizumab. There were no injection site reactions, and no anti-ibalizumab antibodies emerged.
Seven days after people got the 2000 mg loading dose of ibalizumab and started the optimised background regimen, 76% had at least a 0.5 log drop in viral load, and 57% had at least a 1 log (10-fold) drop.
Among 24 people who reached week 24, median viral load fell 2.6 log copies/mL (about 400 copies), 46% had a viral load under 50 copies/mL, and 71% had a load below 400 copies/mL. Eighteen of these 24 (75%) had at least a 1 log drop in viral load. In the first 24 weeks, four people stopped treatment because of an adverse event, three stopped because of virologic failure, and three left the expanded-access programme to start commercially available ibalizumab. In 23 participants, median CD4 count rose from 61 to 93 cells/mm3through the first 24 weeks.
Among 17 people who reached expanded-access week 48, median viral load fell 2.6 log copies/mL, 47% had a viral load below 50 copies/mL, and 59% had fewer than 400 copies/mL. Two thirds of participants (65%) had at least a 1 log fall in viral load. At this point seven people had left the expanded-access program to start commercially available ibalizumab.
The researchers noted that these findings are consistent with results of the phase 3 trial. 
- Emu B, DeJesus E, Berhe M, et al. Ibalizumab efficacy and safety through 48 weeks of treatment: results of an expanded access protocol (TMB-311). IDWeek, October 2-6, 2019, Washington, DC. Abstract 661.
http://natap.org/2019/IDWeek/IDWeek_08.htm (natap report)
- Emu B, Fessel J, Schrader S, et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1. N Engl J Med. 2018;379:645-654.