*Updated on 11/03/2016 at 8:30 AM EST
A phase III trial of the first-ever biologic medication directed against the human immunodeficiency virus (HIV) has demonstrated the safety and effectiveness of the ibalizumab monoclonal antibody in treating previously treated patients who are infected with multidrug resistant HIV-1.
“This long-acting antiretroviral therapy, administered intravenously (IV) every 2 weeks, displays significant activity with an excellent short-term safety profile. The novel mechanism of action provides a new treatment to patients with limited options, with no drug-drug interactions or known risk of cross resistance,” said Jacob Lalezari, MD, lead author of the study and medical director for Quest Research, located in San Francisco, California.
Ibalizumab is a humanized monoclonal antibody that binds to a region of the CD4 receptor on T-cells. It blocks the post-attachment changes of the virus that are necessary before the virus can enter CD4 cells. Patients received 2000 mg IV followed by 800 mg IV after 2 weeks, with the latter dose provided every 2 weeks thereafter.
To be included, patients needed to have a HIV-1 viral load exceeding 1000 copies/mL, had to have been receiving antiretroviral therapy for at least 6 months, and had to have documented resistance to at least one antiretroviral drug from three classes. Those with an active AIDS-related illness, immunomodulatory therapy, steroid, or systemic chemotherapy within 12 weeks of enrollment prior to treatment with ibalizumab, or any grade 3 or 4 abnormality, were excluded.
The 40 patients were 85% male and 45% non-white; they had been infected with HIV for a long time, with a mean duration of infection of 21 years. Of the patient group, 28% had been previously treated with 10 or more antiretroviral drugs.
Despite this dismal treatment history, 83% of patients displayed a virologic response to the drug. Benefits were evident in 33 patients (83% of the total) after the first week of treatment, with a decrease in viral load of 0.5 log10. In contrast, prior to the start of treatment, the existing treatments had been similarly effective related to treatment in only one patient.
No patient discontinued treatment and no serious adverse events occurred. Adverse events that did occur were mild and included dizziness (10% of patients), fatigue (5%), nausea/vomiting (5%), and rash (2.5%).
“This drug benefits a small but challenging population of HIV patients who are highly treatment experienced,” said Daniel R. Kuritzkes, MD, chief of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston, during a press briefing to present the study findings. “This will not be a first- or second-line therapy for those who are infected with HIV, but it may be helpful for certain patients.”
Jacob Lalezari: Employee of Quest Clinical Research Inc.; Research support from AbbVie, Arrowhead, Bavarian Nordic, Bristol-Myers Squibb, Calimmune, CytoDyn, Genocea Biosciences, Gilead Sciences, GlaxoSmithKline, Jansenn, Merck, Novira Therapeutics, Sangamo BioSciences, TaiMed Biologics, and ViV Healthcare
- Photos and tape of IDSA presentation
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; Jacob Lalezari, MD, Quest Clinical Research, San Francisco, CA
Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at firstname.lastname@example.org.
Editor's Note: The following error in the original version of this article has been corrected: benefits after the first week of treatment were seen in 33 patients; the article originally read as "24 patients." Furthermore, the following addition has been made: “trial participants had to have had documented resistance to at least one drug ‘from three different classes.’”
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