No one can deny that many patients can now suppress their HIV with
effective antiretrovirals (ARVs) that cause fewer side effects. However,
a vulnerable and often forgotten minority of people are still
struggling with multi-drug resistant HIV (MDR-HIV) while they anxiously
wait for access to lifesaving ARVs that would finally control their
viral replication. Although some of these patients may have developed
resistant HIV due to lack of adherence or other issues, many of them have been strictly following their doctors' orders for years.
They're often veterans of drug development research who have
accumulated HIV resistance as they repeatedly joined ARV studies or
traditional expanded access programs of a single new drug out of
desperation to control their HIV viral load.
As they signed up for studies that helped companies get their drugs
approved by the FDA (U.S. Food and Drug Administration), many of these
patients were exposed to suboptimal HIV regimens (namely, functional
monotherapy or the addition of a single new active ARV to a failing HIV
regimen).
Currently, the U.S. Department of Health and Human Services (DHHS)
adult HIV treatment guidelines recommend three ARVs be given in
combination to suppress HIV. But many patients have HIV that has mutated
rendering their virus multi-drug resistant. Those with MDR-HIV cannot
construct a viable HIV suppressive regimen with current FDA-approved and
commercially available ARVs.
A new HIV medication called Ibalizumab may be approved this year for
patients with limited treatment options. It has a completely new mode
of action, so most patients should respond to it when using it with at
least one other active agent. It is different from the entry inhibitor maraviroc (Selzentry, Celsentri) in that it blocks the CD4
receptor on T cells rather than blocking the CCR5 co-receptor. This
means it could be effective against virus that uses either the CCR5 or
CXCR4 co-receptor. It is a genetically engineered monoclonal antibody
administered once every two weeks intravenously.
In the manufacturer's website (Taimed Bilogics), the drug is
described as : "TMB-355(Ibalizumab) is a humanized monoclonal antibody
(mAb) and a member of an emerging class of HIV therapies known as
viral-entry inhibitors. This drug candidate is distinct from other entry
inhibitors in that it binds to the CD4
molecule, the primary receptor for HIV infection, thereby interfering
with the penetration of the virus into the cell. It is the first
entry-blocking humanized mAb to treat HIV/AIDS. TMB-355 caught the
attention of the scientific community in February 2003, when results
from the phase-1, single-dose, intravenous infusion (i.v.) clinical
trial showed a transient but clinically significant reduction in the
patients' viral load.
Moreover, it was well tolerated with no evidence of adverse effects on
CD4 T-cells of treated subjects unlike the majority of approved drugs
for HIV. U.S. FDA granted TMB-355 fast track status in October 2003. The
phase-2a clinical trial was successfully completed in 2006, with the
results showing a clean safety profile and clear antiviral activity
(10-fold reduction in viral load). The Phase-2b clinical trial was also
successfully completed in 2011, with the confirmation of a good safety
profile and strong antiviral activity in HIV patients with multidrug
resistance (MDR). U.S. FDA granted orphan drug designation of TMB-355
for HIV patients with multidrug resistance in 2014. Moreover, TaiMed
received breakthrough therapy designation from the U.S. FDA for TMB-355
in 2015, which provides the privilege for a rolling biologics license
application (BLA) submission. A pivotal phase-3, single-arm clinical
trial with patient number of 40 had completed in October, 2016. The
clinical trial results, along with other available CMC, pre-clinical,
and clinical data, will be submitted as BLA package in 2016 under
rolling review. TaiMed Biologics also developed a subcutaneous injection
(s.c.) dosage form and the phase-1 human pharmacokinetics bridging
study was completed in 2012. Currently, TMB is also developing an
intramuscular injection (i.m.) dosage form and a phase-1/2 study for
HIV-negative and naive HIV-positive subjects had completed in 2016.” Source
The manufacturer of this biologics product is now providing free access of this treatment option via their expanded program.
Talk to your doctor about this option if you have been told that your
virus has resistance to nucleosides, non-nucleosides and protease
inhibitors. Remember: This product needs to be used with at least one
more active drug to which your virus has not developed resistance.
Failure to do so will result in resistance to ibalizumab.
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