Bristol-Myers Squibb’s clinical candidate
represents a new class of drugs potentially able to address unmet
medical needs in HIV-1 patients
Proof-of-concept study supports BMS-955176
as a viable compound that overcomes limitations seen in studies of
earlier maturation inhibitor candidates; Phase IIb studies for
BMS-955176 will begin in second quarter of 2015
Bristol-Myers Squibb Company (NYSE:BMY) today announced data
supporting the clinical development of BMS-955176, an
investigational component designed to prevent the maturation of
HIV-1. Presented yesterday in a late-breaking oral presentation and
a poster presentation at the 2015 Conference on Retroviruses and
Opportunistic Infections (CROI) in Seattle, the Phase IIa study
findings confirm the antiretroviral activity of BMS-955176 as an
HIV-1 maturation inhibitor and support its further clinical
development.
BMS-955176 is designed to inhibit one of the last steps of the
HIV-1 viral lifecycle, resulting in the release of immature
non-infectious HIV-1 particles to potentially provide a new
approach to attacking the virus. In the proof-of-concept study,
this next-generation maturation inhibitor drug candidate
demonstrated antiviral activity in the presence of baseline HIV
mutations not responsive to bevirimat, an earlier maturation
inhibitor investigational candidate. BMS-955176 achieved maximum
median declines of -1.70 log10 c/mL in HIV-1 RNA at a dose of 40 mg
once daily, with a plateau of ~1.64 log10 c/mL observed at 40–120
mg once daily. The study’s primary endpoint of change in HIV-1 RNA
from baseline to Day 11 of greater than -1 log10 c/mL in HIV-1 RNA
was met.
“Targeting HIV-1 later in its viral lifecycle is an important
progression for antiviral therapy,” said Dirk Schürmann, M.D.,
Charité Research Organisation GmbH, Berlin, Germany. “The need for
new drug classes is growing, as patients start treatment earlier,
stay on treatment longer, develop viruses that are cross-resistant
to multiple classes, and face long-term safety and tolerability
issues associated with some of the current HIV therapies. Early
data on BMS-955176 illustrate that it is a viable maturation
inhibitor candidate for further study.”
Maturation is one of the final steps in the lifecycle of HIV,
and it occurs when the virus breaks connections between structural
proteins, which allow them to undergo changes that result in the
production of fully mature infectious virus particles that are
subsequently released from cells, with the ability to infect new
CD4+ cells. BMS-955176 is designed to inhibit the last cleavage
step in the HIV maturation process, and by doing so, to block the
virus from becoming mature and infectious.
In this proof-of-concept study, BMS-955176 showed similar
maximum median declines in HIV-1 RNA against un-mutated
(“wild-type”) HIV-1 or HIV-1 with naturally-occurring mutations
(“gag polymorphisms”) at doses of 40, 80, and 120 mg once daily.
There were no deaths, serious adverse events, adverse events (AEs)
leading to discontinuation, grade 3–4 related AEs or clinically
relevant grade 2–4 laboratory abnormalities. With all reported AEs
except for G1-2 diarrhea in 4 subjects on BMS-955176, the same or
greater percentage of subjects on placebo reported AEs as compared
to subjects receiving BMS-955176. Subjects receiving placebo
reported headache (42%), abnormal dreams (25%), night sweats (8%),
and diarrhea (0%).
There are now 34 million people infected with HIV globally, and
more than two decades of treatment advances are helping many of
them live longer than ever. As the patient population ages and
patients are on treatment longer, those developing resistance to
existing regimens and classes, or who are unable to tolerate
current available treatments, is increasing. This drives the need
for new drug classes that not only attack the virus in novel ways,
but also help preserve future treatment options, especially for
treatment-experienced patients. Bristol-Myers Squibb’s HIV pipeline
is primarily aimed at addressing the significant and growing unmet
medical needs of individuals living with HIV, especially among
treatment-experienced patients in need of new treatment
options.
“We are encouraged by the early data on BMS-955176, which
support continued research of the next-generation investigational
treatment for HIV,” said Douglas Manion, M.D., head of Specialty
Development, Bristol-Myers Squibb. “Together with our
investigational attachment inhibitor and currently marketed
therapies, we are continuing our decades-long commitment to HIV
research and development by seeking to build an array of treatment
options designed to address the unmet needs of all people living
with HIV, from those who are new to treatment, to the growing group
of treatment-experienced patients with limited choices among
available regimens.”
Study Design and Results
The Phase IIa, randomized, multi-part trial evaluated BMS-955176
antiviral activity, safety, and exposure-response during 10 days of
monotherapy in 40 HIV-1, subtype B-infected patients with HIV-1 RNA
≥5000 c/mL and CD4+ T-cell counts ≥200 cells/µL. Patients were
randomized 1:1:1:1 to dose groups of 5, 10, 20 or 40 mg, and then
4:1 to receive an oral suspension of BMS-955176 (n=48) or placebo
once daily (n=12) for 10 days. Twenty additional subjects were
later randomized to 80 and 120 mg once-daily dose groups. The
primary endpoint was change in HIV-1 RNA from baseline to Day 11,
and safety and exposure-response were secondary endpoints.
Median change in HIV-1 RNA from baseline to Day 11 ranged from
−0.15 to −1.36 log10 c/mL, and maximum median change between
baseline and Day 24 (study discharge) ranged from −0.50 to −1.70
log10 c/mL across the BMS-955176 groups. There was an increase in
maximum median response over the range of 5–40 mg, which plateaued
at ~–1.64 log10 c/mL at doses of 40–120 mg. Maximum median declines
in HIV-1 RNA were similar for the 40–120 mg once-daily dose groups
regardless of baseline Gag polymorphisms (positions evaluated:
V362, Q369, V370, and T371).
About Bristol Myers-Squibb’s HIV Portfolio
For more than 20 years, Bristol-Myers Squibb has focused on the
discovery, development and delivery of innovative medicines to help
meet the needs of patients living with HIV-1. Today, at least one
in every three U.S. patients with HIV is prescribed a Bristol-Myers
Squibb therapy, and current studies are ongoing for a range of new
treatments in addition to BMS-955176, including a novel HIV-1
attachment inhibitor (BMS-663068).
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases. For more
information, please visit http://www.bms.com or follow us
on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based
on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement
can be guaranteed. Among other risks, there can be no guarantee
that clinical trials of BMS-955176 will support regulatory filings,
or that BMS-955176 will receive regulatory approval in the United
States, or if approved, that it will become a commercially
successful product. Forward-looking statements in this press
release should be evaluated together with the many uncertainties
that affect Bristol-Myers Squibb's business, particularly those
identified in the cautionary factors discussion in Bristol-Myers
Squibb's Annual Report on Form 10-K for the year ended December 31,
2014, in our Quarterly Reports on Form 10-Q and our Current Reports
on Form 8-K. Bristol-Myers Squibb undertakes no obligation to
publicly update any forward-looking statement, whether as a result
of new information, future events or otherwise.
Bristol-Myers Squibb CompanyMedia:Robert PerryOffice:
609-419-5378Cell:
407-492-4616rob.perry@bms.comorInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.com
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