Fostemsavir Bright Spot in Improving [603855]

Fostemsavir Bright Spot in Improving
Virologic Suppression in Resistant HIV
Patients
By Tom Rosenthal
Rates of virologic suppression and immunologic response increased from weeks 48
to 96 in a phase 3 clinical trial evaluating the safety and efficacy of fo stemsavir (ViiV
Healthcare) for a difficult -to-treat population with multi -drug-resistant HIV -1,
according to findings presented at the 2019 International AIDS Society Conference
of HIV Science (IAS 2019), in Mexico City.
The BRIGHTE study is a two -cohort randomized and nonrandomized clinical trial
evaluating investigational fostemsavir used with optimized background treatment
(OBT) after day 8 in heavily treatment -experienced (HTE) adults with HIV, explained
Max Lataillade, MD, the vice president of Clinic al Development at ViiV Healthcare,
who presented the results at a press conference.
“Fostemsavir is a first -in-class investigational attachment inhibitor with a unique
mechanism of action [MOA], as it works by binding directly to the gp120 subunit of
the v irus, and preventing any interaction between gp120 and our CD4 T -cell
receptors, thereby blocking attachment and entry into our CD4 T cells and other
immune cells,” Dr. Lataillade told Infectious Disease Special Edition. “Currently,
available entry inhibit ors have different MOA, and only start working after the virus is
already bound to our CD4 T cell.”
Multidrug -resistant HIV has left these HTE participants in the BRIGHTE study with
few or no treatment options, according to Dr. Lataillade, who added that t hey had
exhausted most or all antiretroviral [ARV] classes. “They rep -resent the highest
unmet medical need,” he said.
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“Due to the lack of treatment options remaining for HTE people living with H IV,
investigating compounds with novel MOA with no cross -resistance to other ARV
classes is important for this population,” he said.
The BRIGHTE study enrolled 371 patients with documented resistance, intolerability
and/or a contraindication to all ARV age nts in at least four of the six available ARV

classes. These patients were randomly assigned 3:1 to add blinded fostemsavir or
blinded placebo (n=272) to their current failing regimen for eight days of functional
mono -therapy (abstract 3372).
Patients with out any remaining fully active approved ARVs (n=99) were assigned to
the nonrandomized cohort and received open -label fostemsavir plus OBT on day 1.
Eighty -six percent of the study participants had diagnoses of AIDS, and 75% had
CD4 counts of less than 200 cells/mcL, according to Kimberly Smith, MD, the head
of Global Research and Medical Strategy at ViiV Healthcare.
The primary end point of the study was mean change in log10 HIV -1 RNA between
days 1 and 8. Beyond the eight -day blinded period, all patients in the randomized
cohort received open -label fostemsavir plus OBT. Key sec -ondary end points
included durability of response at weeks 24, 48 and 96, as well as safety changes
from baseline CD4 -positive cell counts and emergence of viral resistance.
The vir ologic response at week 96 for the randomized cohort increased from week
48 and was comparable across most subgroups, except those with well -established
predictors of reduced response (high baseline viral loads, low baseline CD4 count).
“At week 96, 60% of patients receiving fostemsavir plus OBT in the randomized
cohort (n=163/272) achieved vi -rologic suppression (HIV -1 RNA <40 copies/mL), an
increase of 6% from week 48 results,” Dr. Lataillade said.
Dr. Lataillade said he was impressed b y the increase from 54% at week 48 to 60% at
week 96 of study patients who achieved virologic success.
Patients in the randomized cohort showed continued immunologic improvement
through week 96. They saw an increase in CD4 -positive T -cell counts, as
demons trated by a mean change from baseline of more than 205 cells/mcL (a mean
increase of 66 cells/mcL from week 48), Dr. Lataillade said.
In the randomized cohort at week 96, 67% of patients with a baseline CD4 count of
less than 200 cells/mcL in -creased their CD4 counts to above 200 cells/mcL, and
56% of patients with a baseline CD4 count of less than 50 cells/mcL increased to a
CD4 count of at least 200 cells/mcL, according to Dr. Lataillade.
In addition to the week 96 analysis, a prespecified subgroup analys is across age,
sex and race, among other fac -tors, was also conducted and presented at IAS 2019.
They saw comparable immunologic improvements across all subgroups analyzed,
including a mean increase of 240 cells/mcL in participants with baseline CD4 counts
less than 20 cells/mcL. In addition, the treatment was generally well tolerated.

“People living with HIV who are heavily treatment -experienced have few options
available to them due to the complexities of resistance, safety, tolerability,
contraindication s and prior treatment failure,” Dr. Smith said.
“We believe searching for new ways to prevent the virus from replicating is
important, especially for those who develop resistance to their treatment regimens,
and the findings from BRIGHTE reinforce fostemsa vir as a potential treatment option
for these individuals,” Dr. Smith said.
“These are individuals who are basically running out of treatment options,” Dr. Smith
said at a news conference.
Through week 96, almost all patients who received fostemsavir exper ienced at least
one adverse event, the most common of which were nausea, diarrhea and
headache, respectively. At least one serious adverse event was experi -enced by
38% of the total treated patients, the most common of which were attributed to
infections o r infestations.
There were 29 deaths reported by week 96. Of those, seven were AIDS -related and
11 were acute infections; six were non –AIDS -related malignancies and the
remaining five were due to other conditions. Twenty -three of the 29 deaths (79%)
occurr ed in patients with baseline CD4 -positive T -cell counts less than 50 cells/mm3.
The median baseline CD4 -positive T -cell counts for all patients who died was 11
cells/mm3.
ViiV Healthcare plans to submit fostemsavir to the FDA for approval later this year.