Featured news from NHIVNA
HIV-related news from NAM
HIV attachment inhibitor BMS-663068 matches atazanavir in phase 2b study
Liz Highleyman, 2015-10-14 08:20:00
Bristol-Myers Squibb’s HIV
attachment inhibitor BMS-663068 (fostemsavir), which prevents the virus from
binding to T-cells, demonstrated good antiviral activity and was well-tolerated
at 24 weeks, according to study results published recently in Lancet HIV. Findings from a subgroup analysis at 48 weeks,
presented at the IDWeek 2015 conference in San Diego, showed that response
rates were similar regardless of demographic characteristics, baseline viral
load or CD4 cell count.
therapy (ART) consists of drugs that target different steps of the HIV
lifecycle. None of the currently approved drugs block the first
step, initial attachment of the virus to a host cell; fusion inhibitors like
enfuvirtide (Fuzeon) affect a
slightly later step. Drugs that work in
novel ways are particularly important for people with HIV who have taken lots
of different treatments already (highly treatment-experienced people) and who have
extensively drug-resistant virus.
BMS-663068 is a pro-drug or precursor of BMS-626529,
which binds directly to the gp120 protein that makes up part of the ‘spikes’ on
HIV’s outer surface, thereby preventing viral attachment to CD4 T-cells. Unlike
maraviroc (Celsentri), BMS-663068
binds to the virus itself, not to the cells, and it is active against HIV that uses either CCR5 or CXCR4 co-receptors.
Study AI438011 looked at the safety, efficacy and
dose-response characteristics of BMS-663068 in previously treated people with
HIV. Trial participants were randomised to receive either BMS-663068 or
ritonavir-boosted atazanavir (Reyataz)
as part of a combination regimen.
Jay Lalezari of Quest Clinical Research in San Francisco and colleagues published
24-week primary results from this ongoing trial in the October issue of Lancet HIV. These results were previously presented in part at the 2014 Conference on
Retroviruses and Opportunistic Infections (CROI). The 48-week results were presented in part at this year’s CROI.
The study enrolled 254
participants at 53 hospitals and outpatient clinics in ten
countries in Europe, North and South America, and Africa between July 2011 and
July 2012. A majority (60%) were men, 38% were white, 30% were black and the
median age was 39 years.
Overall, participants had relatively
advanced disease, with a mean CD4 count of 230 cells/mm3, nearly 40%
having less than 200 cells/mm3 and just over 40% having high baseline viral load. Many had experienced
treatment failure on first- or second-line ART and about half had at least one
major mutation conferring resistance to at least one widely used antiretroviral
drug class; however, to participate they were required to still have virus that was sensitive to BMS-626529 and other drugs
used in the study.
were randomly allocated to five treatment arms receiving BMS-663068 at doses of
400 or 800mg twice daily, 600 or 1200mg once daily, or 300/100mg atazanavir/ritonavir.
Everyone also took 400mg raltegravir (Isentress)
and 300mg tenofovir disoproxil fumarate (Viread).
Of note, participants receiving BMS-663068 had a higher daily pill burden,
which could have an effect on adherence.
response rates, or the proportion of participants with viral load <50
copies/ml, were statistically similar across study arms in the 24-week primary
analysis and at 48 weeks:
- BMS-663068 400mg
twice-daily: 80% at 24 weeks and 82% at 48 weeks
- BMS-663068 800mg
twice-daily: 69% and 61%, respectively
- BMS-663068 600mg
once-daily: 76% and 69%, respectively
- BMS-663068 1200mg
once-daily: 72% and 68%, respectively
75% and 71%, respectively.
Mean CD4 cell
gains at 48 weeks were also similar across treatment arms.
generally safe and well-tolerated at all doses tested. At 24 weeks, 7% of participants
in all BMS-663068 groups combined experienced serious adverse events, compared
with 10% in the boosted atazanavir group. Just 2% of BMS-663068 recipients and
4% of boosted atazanavir recipients discontinued treatment early due to adverse
events. None of the serious adverse events or events leading to treatment
discontinuation were considered related to BMS-663068. No notable trends in
laboratory abnormalities were seen in the BMS-663068 group, while boosted
atazanavir was more likely to cause elevated bilirubin.
“In a comparison with ritonavir-boosted
atazanavir, efficacy and safety of BMS-663068 up to the week 24 analysis
support continued development of BMS-663068, which is being assessed in a phase
3 trial in heavily treatment-experienced individuals,” the Lancet HIV study authors concluded.