Ibalizumab (Trogarzo)

Ibalizumab (Trogarzo) is a laboratory-manufactured antibody that binds to the CD4 receptor on T-cells. The antibody is described as a post-attachment inhibitor because it prevents the HIV gp120 protein from changing its shape to engage with co-receptors after it engages with the CD4 receptor. It is the first HIV post-attachment inhibitor.

It is also known as ibalizumab-uiyk. All monoclonal antibodies have a four-letter suffix designed to describe a specific biological manufacturing process used by the originator of the product. As ibalizumab is only manufactured by one company at present, it is referred to as ibalizumab in this article. Ibalizumab is manufactured and marketed by Theratechnologies.

Ibalizumab received marketing approval by the Food and Drug Administration (FDA) in the US in March 2019 and by the European Medicines Agency (EMA) in September 2019 for use by heavily treatment-experienced adults with multi-drug resistant HIV who are unable to construct an antiretroviral regimen to suppress HIV.

Ibalizumab is given as an infusion every two weeks. The infusion is given by a drip feed into a vein and must be given in a clinic. Treatment begins with an infusion of 2000mg and then 800mg every two weeks afterwards. The first infusion will last at least half an hour.

Ibalizumab was approved on the basis of a phase 3 single-arm clinical trial in 40 heavily treatment-experienced people with HIV. Participants were required to have a viral load above 1000 copies/ml and resistance to at least one drug in each of three antiretroviral drug classes. Fifty per cent of participants had resistance to all the drugs in three antiretroviral classes and 33% to drugs in four classes. Participants received an initial ibalizumab dose of 2000mg followed by seven days of monotherapy before the addition of a background antiretroviral regimen optimised by resistance testing. Participants received an 800mg dose every 14 days during the study and were followed for 24 weeks in total.

Eighty-three per cent of participants experienced a viral load reduction of at least -0.5 log in the seven-day monotherapy period and 60% experienced a reduction of at least 1 log. The median viral load reduction was -1.1 log at the end of the monotherapy period.

At the end of the follow-up period, 43% had a viral load below 50 copies/ml and 50% had a viral load below 200 copies/ml. Forty-three per cent required the addition of another investigational agent, fostemsavir, to construct a viable background regimen.

Extended follow-up of 27 participants who completed the phase 3 study and continued to receive ibalizumab in an expanded access programme after the end of the trial showed 67% had a viral load below 50 copies/ml at week 48. All 15 people who had a viral load below 50 copies/ml at week 25 maintained an undetectable viral load at week 48.

Mild to moderate diarrhoea was the most common side-effect of ibalizumab in the phase 3 clinical trial. Rash, dizziness, headache, nausea (feeling sick), fever, vomiting and nose and throat infections were each reported by at least 10% of participants in the study. Infusion site reactions were not reported by any study participants. Analysis of phase 2 clinical trials also found that dizziness, headache, paraesthesia (altered taste), dry skin, dermatitis and tiredness were reported by at least one in ten participants.

Glossary

viral load

Measurement of the amount of virus in a blood sample, reported as number of HIV RNA copies per milliliter of blood plasma. Viral load is an important indicator of HIV progression and of how well treatment is working. 

 

trial

A clinical trial is a research study that evaluates a treatment or intervention with human volunteers, in order to answer specific questions about its safety, efficacy and medical effects.

antiretroviral (ARV)

A substance that acts against retroviruses such as HIV. There are several classes of antiretrovirals, which are defined by what step of viral replication they target: nucleoside reverse transcriptase inhibitors; non-nucleoside reverse transcriptase inhibitors; protease inhibitors; entry inhibitors; integrase (strand transfer) inhibitors.

phase III

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.

antibody

A protein substance (immunoglobulin) produced by the immune system in response to a foreign organism. Many diagnostic tests for HIV detect the presence of antibodies to HIV in blood.

Rash related to ibalizumab is usually mild to moderate and occurs within one to three weeks of the first infusion. Rash usually disappears after one to three weeks without discontinuation of treatment.

Loss of susceptibility to ibalizumab was noted in nine out of ten people who experienced virological rebound or non-response in the phase 3 clinical trial and this was associated with changes in the V5 loop of HIV-1 gp120.

As ibalizumab is an antibody it is not expected to have any interactions with other medicines.

Ibalizumab should be used with effective contraception. Ibalizumab should not be used during pregnancy or while breastfeeding.

Ibalizumab has not been tested in children and is not licensed for use in people under the age of 18.

References

Emu B et al. Phase 3 study of ibalizumab for multi-drug-resistant HIV-1. New England Journal of Medicine 379: 645-654, 2018 (open access).

DOI: 10.1056/NEJMoa1711460

Cohen Z et al. Analysis of patients completing the ibalizumab phase 3 trial and expanded access program. International Congress on Drug Therapy in HIV Infection (HIV Glasgow), Glasgow, 2018, abstract O345. You can read more about this study in our news report.

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