Peter Ackerman of ViiV Healthcare, who are developing
fostemsavir, presented 48-week results from the BRIGHTE study of fostemsavir in
highly treatment-experienced people. All participants in the study were failing their current antiretroviral
therapy (ART) and had viral loads over 400 copies/ml.
BRIGHTE was split into two different cohorts according to
whether there were any other functional antiretroviral drugs that could be used
in an optimised background regimen (OBR) or not.
If people had one or two functioning drugs in at least two
classes of ARVs that could be used to construct an OBR, then they were briefly
randomised – just for eight days – to continue on their failing regimen and
receive either fostemsavir or a placebo. Those receiving the active drug were thus essentially receiving fostemsavir
monotherapy. After eight days, everyone received open-label fostemsavir plus the best OBR
that could be constructed.
If people had no functional antiretroviral drugs left, then
they were immediately put on open-label fostemsavir plus an OBR in what Ackerman said was “as
much of a compassionate release programme as a drug trial.” Investigational
drugs were allowed in the OBRs in this group; 15 people, for instance, were
also taking ibalizumab.
There were 371 people in BRIGHTE. Ninety-nine were in the
no-drugs-left, immediate treatment cohort and of the remaining 272, 203 were
randomised to receive fostemsavir in the initial eight-day period, and 69
placebo.
This was a very treatment-experienced and in many cases very
unwell group of people. Their average age was 49, just under a quarter were women
and a similar proportion were African American.
Their average viral load at baseline was 4.6 log copies/ml (40,000
copies/ml).
Three-quarters of them had CD4 counts below the
AIDS-defining limit of 200 cells/mm3. Thirty-five per cent in the
randomised group and 54% in the immediate-treatment group had a CD4 count below
50 cells/mm3, and 26% and 40% respectively had CD4 counts below 20
cells/mm3.
Given these life-threatening CD4 counts, it is not that
surprising that 20 people died during the study, eight in the randomised group
and 12 in the immediate-treatment group.
Virtually all people had treatment experience with the
NRTI, NNRTI and protease inhibitor drug classes. With integrase inhibitors, 75% of the
randomised group and 95% of the immediate-treatment group had experience. Thirty-nine per cent in the randomised group and 69% in the immediate-treatment group had
taken the fusion inhibitors T-20 or T-1249. Twenty-six per cent and 40% respectively had taken a CCR5 inhibitor
like maraviroc.
During the eight days of randomisation, people on
fostemsavir experienced an 0.8 log copies/ml drop (about a 6.5-fold drop) in
viral load compared with an 0.2 log drop in those on placebo.
At week 48, in a strict analysis that defined any change in OBR as a
regimen failure, a viral load below 40 copies/ml on their regimen was achieved by 54% of people in the randomised group and 38% of those in the immediate-treatment
group.
Black participants in the study did somewhat better,
with 65% with a viral load below 40 copies/ml vs 50% of other people, as did women (61%
below 40 copies/ml vs 51% men). People with a baseline viral load over
100,000 copies did worse (35% below 40 copies/ml at week 48) and people
with very low CD4 counts at baseline were more likely to fail (36% viral load below
40 copies/ml at week 48).
In a less strict analysis that allowed changes in the OBR,
62% in the randomised group had a viral load below 40 copies/ml and 48% in the
immediate-treatment group. If viral load failure was defined more liberally as
a viral load over 400 copies/ml, then 86% in the non-randomised group and 55%
in the immediate-treatment group had a successful virologic response.
People in the randomised group experienced an average
increase of 139 cells/mm3 in their CD4 counts, from 100 cells/mm3
at baseline to 239 at week 48. The average increase in the immediate-treatment
cohort was 64 cells/mm3, from 41 cells cells/mm3 at baseline
to 105 at week 48.
Safety, in this highly experienced and unwell population,
was generally good, with the most common ones being nausea, diarrhoea and
headache. But 33% in the randomised group and 44% in the immediate group had
to discontinue their regimen at some point.
Peter Ackerman commented that “week 48 results from the
ongoing BRIGHTE study support further development of fostemsavir as a
therapeutic option for HIV-1-infected highly treatment-experienced patients
with multi-drug resistance and few remaining active therapies.”
