Ibalizumab infusion reduces viral load in people with HIV multi-drug resistance

29 November 2016. Related: Antiretrovirals.

Simon Collins, HIV i-Base

After almost a decade with limited or no development, during which this compound was shuffled between companies, preliminary results from a phase 3 study show antiviral efficacy of the monoclonal antibody ibalizumab in people with multi-drug resistant HIV.

The results were presented at the US conference IDWeek by Jay Lalezari from Quest Clinical Research, San Francisco. Unfortunately, this conference provides only the programme and abstracts online, from which this report is written, but not slides or webcasts.

The current study (TMB-301) is an ongoing single-am study in 40 participants with MDR HIV with detectable viral load on their current combination. [2]

Ibalizumab works by attaching to CD4 receptors and blocking conformational changes that are needed to enter the cell. It is given using an intravenous (IV) infusion every two weeks.

The study design included:

1. Monitoring control phase from day 0 to 6 on the current failing combination.
2. Adding a single loading dose 2000 mg dose of ibalizumab on day 7.
3. Optimising background HIV drugs on day 14 to include at least one sensitive new drug (for 43% of participants this was an investigational compound).
4. From day 21 onwards, 800 mg ibalizumab was given every two weeks.

The primary endpoint results are the percentage of participants with >0.5 drop in viral load at day 14.

Limited baseline demographics included mean age 51 years, 15% women and 45% non-Caucasian. Mean duration of HIV infection was 21 years, with participants having used a mean of 10 previous antiretrovrials. Mean CD4 count was 161 cells/mm³ with 50% <100 cells/mm³ and one-third <10 cells/mm³. Mean viral load was 100,000 copies/mL with 18% of participants having viral load above this.

At baseline, 50% of participants had resistance to at least three classes, with major mutations to NRTIs, NNRTIs, PIs and INIs on 93%, 85%, 83% and 61%, respectively.

On day 14, mean and median viral load reductions were 1.1 log copies/mL. Viral load reductions of at least 1.0 log copies/mL were reported for 17/38 participants (60%) and 33/38 (83%) had reductions >0.5 log copies/mL (both p <0.0001, compared to control period).

No treatment related serious side effects or discontinuations were reported during days 0-14. The study is ongoing and will continue until week 24. A further phase 3 study is also ongoing. [3]

Comment

This compound has such a slow development pathway, that the chance to see results is important. Phase 1b efficacy results were first reported in 2008. [4]

Ibalizumab is being developed by the Taiwanese company TaiMed but marketing and distribution rights for the US and Canada have been sold to Theratechnologies, whose only other product is tesamorelin (Egtifta) to treat visceral hypertrophy.

Top level results from this study were announced in a press release in May 2016. [5]

References:

1. Lalezari J et al. Primary efficacy endpoint and safety results of ibalizumab (IBA) in a phase 3 study of heavily treatment-experienced patients with multi-drugs resistant (MDR) HIV-1 infection. ID Week, 26-30 October 2016. Late breaker oral abstract LB-6.
   http://www.idweek.org
   http://www.natap.org/2016/IDSA/IDSA_06.htm
2. Ibalizumab plus optimized background regimen in patient with multi-drug resistant HIV.
   https://clinicaltrials.gov/ct2/show/study/NCT02475629
3. Ibalizumab plus optimized background regimen in treatment-experienced patients with multi-drug resistant HIV-1
   https://clinicaltrials.gov/ct2/show/NCT02707861
4. Jacobson JM et al. Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults. Antimicrob Agents Chemother. 2009; 53:450-7.
   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630626
5. Theratechnologies press release. Theratechnologies announces that 82.5% of patients achieved the primary endpoint in the phase III ibalizumab trial. (24 May 2016).
   https://theratechnologies.s3.amazonaws.com/prod/media/nr-th-10042017-en.pdf
   (PDF)