This is my 46th powerpoint....that deals with IBALIZUMAB: The first monoclonal antibody for HIV infection!!! It deals with its mechanism, background history, safety & kinetic profiles, and other relevant details. Happy reading!! :)

1. PRESENTED BY:
VISHNU.R.NAIR,
5TH YEAR PHARM.D
NATIONAL COLLEGE OF PHARMACY(NCP).
LUNCH BREAK SEMINAR
Event ID: NCP/LBS/2018/015
Date : 21/04/2018

2.  In the current scenario  HIV treatment includes 27 medications from 5 different classes
 Despite proven benefits & efficacy of ARV(Anti-retroviral treatment)  there are rising
concerns, pertaining to numerous ADRs & risks of resistance!
 Thus  there is a need for newer HIV-treatment strategies, with high efficacy & least
toxicities
 Ibalizumab is a monoclonal antibody under the trade name “TROGARZO”
 Approved on March 6, 2018 by the US-FDA, for adult patients, infected with HIV, who are in
refractory state.
 Humanized IgG4 MAb , that was granted “breakthrough therapy”.
Iacob A.S, Iacob.G.D, “Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy”, available at
https://www.ncbi.nlm.nih.gov/pmc/aricles/PMC5711820/14.7959.

3.  Benefits of using monoclonal antibodies in a disease like HIV:
a. Improved antiviral effects  enhanced efficacy!
b. Lesser risks of toxicity
c. Improved resistance profile
d. Enhanced synergistic effects (when given with other ARVs!)
e. Ability to restore CD4 T-cell responses.
f. No risks of immunosuppression!!!
Iacob A.S, Iacob.G.D, “Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy”, available at
https://www.ncbi.nlm.nih.gov/pmc/aricles/PMC5711820/14.7959.

4.  Ibalizumab  comes under the class of “CD4-directed post-attachment HIV-1 inhibitor”
• Drug  shows the following actions:
a. Drug  binds to “domain 2” of CD-4+ T-cells  prevents post-attachment steps (required
for entry of HIV-1 viral particles into host cells)
b. Drug  prevents viral transmission, that occurs via “cell-cell fusion”.
• To be precise :
a. Ibalizumab doesn’t prevent viral attachment to CD-4+ T-cells , but surely prevents viral
entry inside the same!
b. Binding specificity of drug  reduces risks of immunosuppression!!
Iacob A.S, Iacob.G.D, “Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy”, available at
https://www.ncbi.nlm.nih.gov/pmc/aricles/PMC5711820/14.7959.

5. SUMMARIZED MOA OF IBALIZUMAB:

6.  Ibalizumab  administered via i.v infusion/ s.c injection
 According to recent studies  an intramuscular alternative is also being evaluated (Lin et al.,
2017)
 Average half-life of ibalizumab (after s.c injection) is 3-3.5 days  allows “weekly
administration schedule”(Bruno and Jacobson,2010)
Bruno C.J, Jacobson J.M.(2010). Ibalizumab, an anti-CD4 monoclonal antibody for the treatment of HIV-1 infection.
J.Antimicrob.Chemother.65, 1839-1841.10.1093/jac/dkq261 [Pubmed]

7.  Although most studies maintain that ibalizumab is safe  it does have its own share of ADRs
 Mild-moderate dose-dependant effects include(Khanlou et al.,2004; Norris et al.,2006):
a. Rash(14-15%)
b. Diarrhea(0-14%)
c. Headache(7-11%)
d. Nausea(4-11%)
e. Depression(4-11%)
Norris D., Morales J., Gathe J., Godofski E., Garcia F.H.R., et al.(2006). Phase 2 efficacy and safety of the novel entry inhibitor TNX-355, in
combination with optimized background regimen(OBR), in proceedings of the 26th International AIDS Conference (Toronto, DN).

8.  Severe laboratory abnormalities  seen in 9-10% of cases during a 48-week treatment
 No drug-related deaths/ discontinuations occurred in the above mentioned studies
 Intramuscular administration of drug was also safe, without local side effects at the injection
site.
Norris D., Morales J., Gathe J., Godofski E., Garcia F.H.R., et al.(2006). Phase 2 efficacy and safety of the novel entry inhibitor TNX-355, in
combination with optimized background regimen(OBR), in proceedings of the 26th International AIDS Conference (Toronto, DN).

9.  Mainly indicated for HIV-1 infection in previously-treated adults with multidrug-resistant
infection(failing their current ART regimen)
 Used in combination with other ART drugs
 Initially  give “single loading dose” of 2,000 mg i.v (infused in 0.9% NS, for at least 30
minutes)
 Begin “maintenance doses” 2 weeks after loading dose
 If no infusion-related adverse reactions occur  subsequent infusions can be reduced to
no less than 15 minutes.
 Maintenance dose: 800 mg i.v every 2 weeks(infused over 15-30 minutes)
Iacob A.S, Iacob.G.D, “Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy”, available at
https://www.ncbi.nlm.nih.gov/pmc/aricles/PMC5711820/14.7959.

10.  Primary resistance to ibalizumab is estimated at around 10%
 Resistance to ibalizumab  results in a highly infectious viral strain  but does not show
resistance to other ARTs(enfuvirtide, maraviroc, etc)
 Reduced susceptibility to ibalizumab occurs if HIV-1 loses a glycan in the “N-terminus of gp-
120  thus drug susceptibility can be restored by placing a glycan molecule in the variable
region of the antibody.
Iacob A.S, Iacob.G.D, “Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy”, available at
https://www.ncbi.nlm.nih.gov/pmc/aricles/PMC5711820/14.7959.

11.  Ibalizumab is a monoclonal antibody with better anti-HIV-1 activity & lesser side effects
 Induces conformational changes of CD-4 receptors & gp-120  prevents post-CD4 binding
events, without eliciting immunosuppressive responses.
 Also preserves CD-4 T-cell counts
 Since drug has ability to block entry of HIV-1 multi-resistant isolates  it has been studied in
combination with other anti-HIV drugs with favorable results in experienced patients
 Although definitive indications for ibalizumab are yet to be established  ibalizumab is
surely expected to be a part of a “salvage regimen” for the most vulnerable category of HIV
patients, especially those with extensive drug resistance!!!

12. THANK YOU!!!!