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PRO-140 antibody injections maintain viral suppression in phase 2 study
Liz Highleyman, 2016-06-28 07:30:00
Subcutaneous injections of
PRO 140, a monoclonal antibody that blocks HIV entry
into cells, was well-tolerated and maintained undetectable viral load for more
than a year after stopping antiretroviral therapy (ART) in patients with viral
suppression, according to a study presented at the ASM Microbe 2016 meeting last week in Boston.
HIV uses two co-receptors -- CCR5 and CXCR4 -- along
with the CD4 cell surface receptor to enter cells. PRO 140 is a humanized monoclonal antibody that works by blocking CCR5, thereby preventing HIV from getting into cells and
replicating. About 70% of people with HIV in the US, and up to 90% of newly
diagnosed people, have CCR5-tropic virus.
showed that a single intravenous injection of PRO 140 dramatically reduced HIV levels,
and weekly subcutaneous (under the skin) injections reduced viral load
significantly more than placebo. Results to date suggest that PRO 140 does not
negatively affect normal immune functions mediated by CCR5.
PRO 140 was
initially developed by Progenics but was acquired by CytoDyn in 2012. Clinical
trial data on PRO 140 has not been presented at scientific conferences or in
medical journals for several years, but CytoDyn has issued numerous press
releases tracking its progress.
Paul Maddon, a
scientific advisor at CytoDyn, presented findings from a phase 2b trial of PRO
140 as maintenance therapy for people who had achieved viral suppression
on standard combination ART.
The CD01 study included 39 HIV-positive
adults with exclusively CCR5-tropic HIV (according to the Trofile DNA
Co-receptor Tropism Assay), viral load below 40 copies/ml on a stable ART
regimen and a CD4 T-cell count above 350 cells/mm3. More than 90%
were men with a median age of 55 years.
All participants in this open-label study
switched, with one week of overlap, from their ART regimen to weekly 350mg
subcutaneous injections of PRO 140 monotherapy for up to 12 weeks. Those who
experienced viral rebound restarted ART.
Among the 28 patients in the cohort
assessing longer-term treatment, 15 people who maintained viral suppression for
12 weeks were trained to self-administer their shots and allowed to continue
PRO 140 maintenance therapy for an additional 108 weeks in an extension phase.
In this group 87% were men, 20% were non-white, the median age was 55, the
median CD4 count was 586 cells/mm3 and they had been diagnosed with
HIV for a median of 13 years.
Of these 15 participants, 10 are still on
PRO 140 without ART after more than a year -- and in some cases approaching two
years. Among patients tested with a single-copy HIV RNA assay, the lowest
median viral load was 0.4 copies/ml.
Of the remaining participants, four
experienced virological failure (two consecutive measurements of >400
copies/ml) and restarted ART, while one relocated and left the study with an
undetectable viral load at 47 weeks.
Participants did not show evidence of drug
resistance, those with virological failure did not experience a change in HIV
tropism -- allowing their virus to enter using CXCR4 instead of CCR5
co-receptors -- and no-one developed antibodies against PRO 140. All patients
who restarted ART regained full viral suppression.
PRO 140 was generally safe and well tolerated.
While overall adverse events were common (more than 90% in the extension
phase), there were no drug-related serious adverse events or treatment
discontinuations for this reason. All drug-related adverse events were local
injection site reactions, usually mild or moderate.
[more than] one year, weekly PRO 140 subcutaneous 350mg provided full viral
suppression, was well tolerated, and enabled the avoidance of potential
toxicity of ART while preserving drug options", the researchers concluded.
"These results support further development of PRO 140 SC as a simple,
long-acting, single-agent maintenance therapy after initial ART in selected
They noted that the extension phase of the
study is on-going, with a plan to further extend PRO 140 monotherapy beyond 120
weeks for patients with continued viral suppression.