Intramuscular injection preferable to IV infusion of ibalizumab for PWH

Ibalizumab delivered via intramuscular (IM) injection is not only safe and well-tolerated but also succeeds in viral suppression among heavily treatment experienced (HTE) people living with HIV (PWH), making IM the preferred method of administration among participants of the TMB-302 study.

“Expanding the administration options for ibalizumab is an important step to increasing access and agency for PWH,” said the researchers headed by Kaitlin R Anstett from Theratechnologies, Inc. in Montreal, Canada. [CROI 2024, abstract 631]

Ibalizumab, a monoclonal antibody, is used to treat multidrug-resistant (MDR) HIV-1 infection, combined with an optimized background regimen, among HTE PWH. Currently, this drug is administered every 2 weeks (Q2W) via intravenous (IV) infusion over 15‒30 minutes or via undiluted IV push over 30 seconds.

“This requires a peripheral IV catheter for administration by trained staff, which can limit access,” the researchers said. “Altering the mechanism of administration of ibalizumab will expand and simplify access for HTE PWH in need of new therapies to achieve their treatment goals.”

In the phase III TMB-302 study, Anstett and her team assessed the safety and efficacy of ibalizumab delivered through an IM injection in clinically stable HIV-1‒infected ibalizumab-experienced patients and healthy HIV-uninfected volunteers. All participants received at least two IV infusions of ibalizumab prior to administration via IM injection for 8 weeks.

Then, the research team administered the HIV treatment satisfaction questionnaire - status (HIVTSQS) and study medication satisfaction questionnaire - status (SMQs) at the last IV infusion administration (day 29) and after 8 weeks of IM administration (day 85), as well as the HIV treatment satisfaction questionnaire – change (HIVTSQC) and study medication questionnaire - change (SMQc) on day 85.

Additionally, all participants answered a one-question preference assessment on day 85 to compare their experience on IM injections with IV infusion.

Ibalizumab administered via IV infusion and IM were both tolerated well by the participants. No statistically significant difference was observed in either the HIVTSQS or SMQs between day 29 and 85. However, 83 percent of HIV-uninfected volunteers and 67 percent of HIV-infected clinical stable participants preferred the IM method over IV infusion.

Most importantly, none of the PWH had failed viral suppression throughout the course of the study. There were also no new or unexpected safety concerns seen.

Resistant HIV infection

Ibalizumab works by blocking HIV-1 from infecting CD4+ cells. It was approved by the Food and Drug Administration, in combination with other antiretroviral (ARV) therapy, for treating HIV-1 infection in HTE adults with MDR HIV-1 infection failing their current ARVs. [Ann Pharmacother 2021;55:230-239]

“IBA demonstrated significant and sustained antiviral activity in patients with MDR HIV-1 infection who had advanced disease and limited treatment options,” said authors Elias B Chahine from Palm Beach Atlantic University Lloyld L. Gregory School of Pharmacy, Florida, US, and Spencer H Durham from Auburn University Harrison School of Pharmacy, Alabama, US.

“It carries a warning regarding the development of immune reconstitution inflammatory syndrome. Common adverse reactions include diarrhoea, dizziness, nausea, and rash,” they added.