 |
|
|
| |
Analysis of Patients Completing the Ibalizumab Phase 3 Trial and Expanded Access Program
|
| |
| |
Reported by Jules Levin
Glasgow 2018 Oct 27-31
Zvi Cohen, PhD
Theratechnologies Inc
Download the PDF here
Download the PDF here
GLASGOW: OUTCOMES OF PATIENTS NOT ACHIEVING PRIMARY ENDPOINT FROM AN IBALIZUMAB PHASE 3 TRIAL - (11/01/18)
NATAP Reports - Glasgow HIV
28 - 31 October 2018
Glasgow, UK
New Updated HHS ART Guidelines Issued Oct 25, 2018 say:
Ibalizumab (IBA), a CD4 post-attachment inhibitor, was recently approved for use in persons with multidrug-resistant HIV. A review of the results of a clinical trial on IBA use in this setting has been added to the section.
.......Patients with ongoing detectable viremia who lack sufficient treatment options to construct a fully suppressive regimen may be candidates for the recently approved CD4 post-attachment inhibitor ibalizumab (IBA).61 A single-arm, multicenter clinical trial enrolled 40 heavily ART-experienced participants who had multidrug-resistant HIV and who were experiencing virologic failure on an ARV regimen. Subjects received intravenous infusions of IBA every 2 weeks in addition to an optimized background regimen that included at least one additional agent to which the subject's virus was susceptible. At week 24, 43% of participants achieved HIV RNA <50 copies/mL, and 50% of participants achieved HIV RNA <200 copies/mL.62 Of the 27 participants who continued on to the 48-week follow-up study, 59% and 63% had HIV RNA <50 copies/mL and <200 copies/mL, respectively. All 15 patients who had HIV RNA <50 copies/mL at week 24 maintained viral suppression up to week 48.63
both pdfs attached-
accompanying publication was FDA Perspective: Ibalizumab in Multidrug-Resistant HIV - Accepting Uncertainty
-----------------------------------------
both pdfs attached-
accompanying publication was FDA Perspective: Ibalizumab in Multidrug-Resistant HIV - Accepting Uncertainty
Abstract
Background
Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4.
Methods
In this single-group, open-label, phase 3 study, we enrolled 40 adults with multidrug-resistant (MDR) HIV-1 infection in whom multiple antiretroviral therapies had failed. All the patients had a viral load of more than 1000 copies of HIV-1 RNA per milliliter. After a 7-day control period in which patients continued to receive their current therapy, a loading dose of 2000 mg of ibalizumab was infused; the viral load was quantified 7 days later. Through week 25 of the study, patients received 800 mg of ibalizumab every 14 days, combined with an individually optimized background regimen including at least one fully active agent. The primary end point was the proportion of patients with a decrease in viral load of at least 0.5 log10 copies per milliliter from baseline (day 7) to day 14.
Results
A total of 31 patients completed the study. The mean baseline viral load was 4.5 log10 copies per milliliter, and the mean CD4 count was 150 per microliter. Of the 40 patients in the intention-to-treat population, 33 (83%) had a decrease in viral load of at least 0.5 log10 copies per milliliter from baseline (P<0.001 for the comparison with the control period). The mean viral-load decrease was 1.1 log10 copies per milliliter. During the control period, 1 patient, who received the optimized background regimen prematurely, had a decrease in viral load of 0.5 log10 copies per milliliter. At week 25, patients who had received ibalizumab plus an optimized background regimen had a mean decrease of 1.6 log10 copies per milliliter from baseline; 43% of the patients had a viral load of less than 50 copies per milliliter, and 50% had a viral load of less than 200 copies per milliliter. Among 10 patients who had virologic failure or rebound, in vitro testing identified 9 who had a lower degree of susceptibility to ibalizumab than at baseline. The most common adverse event was diarrhea (in 20% of patients). Four patients died from causes related to underlying illnesses; 1 had a serious adverse event (the immune reconstitution inflammatory syndrome) that was deemed to be related to ibalizumab therapy.
Conclusions
In patients with MDR HIV-1 infection who had advanced disease and limited treatment options, ibalizumab had significant antiviral activity during a 25-week study. Evidence of the emergence of diminished ibalizumab susceptibility was observed in vitro in patients who had virologic failure. (Funded by the Orphan Products Clinical Trials Grants Program of the Food and Drug Administration and TaiMed Biologics; TMB-301 ClinicalTrials.gov number, NCT02475629.)
------------------------------
|
| |
|
|
|
|
|
