Second-Generation Investigational HIV-1 Maturation Inhibitor Demonstrates Positive New Phase IIa Results, Supporting Continue...
July 21 2015 - 2:00PM
Business Wire
Investigational agent BMS-955176 represents
a novel approach since it is designed to inhibit HIV-1 replication
as compared to currently available treatments
Bristol-Myers Squibb Company (NYSE:BMY) today announced
additional Phase IIa proof-of-concept data for BMS-955176, a novel
investigational agent designed to prevent the maturation of HIV-1.
The study findings, which are being presented in a late-breaking
oral presentation at the 8th IAS Conference on HIV Pathogenesis,
Treatment and Prevention in Vancouver, confirmed the antiretroviral
activity of BMS-955176 when administered with atazanavir (±
ritonavir) and support further development of the second-generation
HIV-1 maturation inhibitor.
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. As part of a multi-part
proof-of-concept study, a two-drug combination of BMS-955176 (80
mg) plus atazanavir (unboosted) had a maximum median change in
HIV-1 RNA of -2.23 log10 c/mL from baseline through study discharge
(Day 42). The standard of care (SOC) control of atazanavir 300 mg
and ritonavir 100 mg plus tenofovir disoproxyl fumarate 300 mg plus
emtricitabine 200 mg in a fixed dose combination had a maximum
median change in HIV-1 RNA of -2.39 log10 c/mL from baseline
through study discharge (Day 42). In addition, a lower dose of
BMS-955176 (40 mg) plus atazanavir and ritonavir had a similar
maximum median change in HIV-1 RNA of -2.20 log10 c/mL. Length of
therapy for all treatment groups was 28 days. Study endpoints
included change in HIV-1 RNA from baseline to Day 28 and from
baseline to the end of the study (Day 42) and safety.
“The BMS-955176 data provide further compelling evidence of its
potential as a second-generation maturation inhibitor that
suppresses HIV-1 in a novel way,” said Douglas Manion, M.D., Head
of Specialty Development, Bristol-Myers Squibb. “The 25 years we
have spent fighting this disease have given us the expertise to
help address the unmet needs in HIV treatment and we are committed
to developing improved solutions for treatment-experienced
patients.”
Study Design and Results
In Part B of the Phase IIa, randomized, multi-part trial,
antiviral activity and safety of BMS-955176 administered with
atazanavir ± ritonavir were evaluated and compared to a standard of
care regimen of atazanavir and ritonavir plus tenofovir disoproxil
fumarate/emtricitabine after 28 days of therapy. The study included
28 HIV-1, subtype B-infected patients with HIV-1 RNA ≥5000 c/mL and
CD4+ T-cell counts ≥200 cells/µL who were randomized 2:2:2:1 to
four treatment groups: BMS-955176 40 mg plus atazanavir 400 mg;
BMS-955176 40 mg plus atazanavir 300 mg and ritonavir 100 mg;
BMS-955176 80 mg plus atazanavir 400 mg; and a SOC control of
atazanavir 300 mg and ritonavir 100 mg plus tenofovir disoproxyl
fumarate 300 mg plus emtricitabine 200 mg in a fixed dose
combination. Study endpoints included change in HIV-1 RNA from
baseline to Day 28, change in HIV-1 RNA from baseline to the end of
the study (Day 42) and safety. A summary of the data is below.
BMS-955176(40mg QD)+ATV
(400mg QD) BMS-955176(40mg QD)+ATV (300mg QD)+RTV (100mg QD)
BMS-955176(80mg QD)+ATV (400mg QD) Tenofovir disoproxil fumarate
(300mg QD)+emtricitabine (200mg QD) (fixed-dose combination)
+ATV(300mg QD)
+RTV (100mg QD)
N 8 8 8 4 Maximum decline in HIV-1 RNA (log10 c/mL); median
(min, max)
-1.86
(-1.49, -2.37)
-2.20
(-1.24, -3.52)
-2.23
(-1.87, -2.68)
-2.39
(-1.83, -3.04)
Median decline in HIV-1 RNA (log10 c/mL) on Day 29 (min, max) -1.66
(-1.19, -2.04)
-1.99
(-1.04, -3.32)
-2.18
(-1.53, -2.68)
-2.22
(-1.83, -2.84)
There were no deaths, serious adverse events or adverse events
leading to discontinuation. In addition, bilirubin levels were
lower for patients receiving BMS-955176 plus unboosted atazanavir
compared to patients receiving BMS-955176 40 mg plus boosted
atazanavir or the standard of care. The most common adverse events
(≥10%) across treatment groups included increased bilirubin levels
(58%), headache (50%) and abnormal dreams (38%).
These study findings follow data reported in February at the
2015 Conference on Retroviruses and Opportunistic Infections
(CROI), which showed that as monotherapy, BMS-955176 demonstrated
strong antiviral activity against HIV-1 regardless of naturally
occurring changes in the Gag polyprotein that were not responsive
to first-generation maturation inhibitor bevirimat.
Taken together, data from Part A and Part B of the Phase IIa
proof-of-concept study support the further evaluation of BMS-955176
in novel treatment regimens such as nucleos(t)ide- and
booster-sparing regimens to address key unmet needs for HIV-1
treatment-experienced patients. Two Phase IIb studies have started
in 2015: a traditional dose-finding study in treatment-naive
patients and a second Phase IIb study to evaluate a nucleos(t)ide-
and booster-sparing regimen in treatment-experienced patients.
As one of the final steps in the HIV-1 lifecycle, maturation
occurs when the virus breaks connections between structural
proteins. The structural proteins are able to then undergo changes,
resulting 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-1 maturation process, which then
blocks the virus from becoming mature and infectious.
Globally, there are 34 million people infected with HIV-1.
Significant treatment advances over the last twenty years have
helped many infected by the disease live longer. However, patients
living with HIV-1, particularly those who are
treatment-experienced, can develop resistance to existing therapies
due to a variety of factors. According to the U.S. Department of
Health and Human Services, data has shown that suboptimal adherence
and drug intolerance/toxicity, for example, accounted for 28% to
40% of virologic failure and regimen discontinuations. Novel
therapies with low potential for cross-resistance can help address
this challenge.
About Bristol Myers-Squibb’s HIV Portfolio
For more than 20 years, Bristol-Myers Squibb has focused on
delivering innovative medicines to help meet the needs of patients
living with HIV-1. Our goal is to help individuals living with
HIV-1 to live longer and healthier lives by achieving and
maintaining viral suppression, and by managing challenges
associated with treatment resistance. We are investigating new ways
to attack the HIV-1 virus, and studies are ongoing for innovative
treatments including the HIV-1 maturation inhibitor and an 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.
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version on businesswire.com: http://www.businesswire.com/news/home/20150721006257/en/
Bristol-Myers SquibbMedia:Robert Perry, 609-419-5378Cell:
407-492-4616rob.perry@bms.comorInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.com
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