|[March 05, 2014]
Bristol-Myers Squibb Presents Promising Phase IIb Data for Novel, Investigational Attachment Inhibitor for HIV-1 Infected Treatment-Experienced Patients
PRINCETON, N.J. --(Business Wire)--
Squibb Company (NYSE:BMY) today presented 24-week Phase IIb data
that demonstrated similar response rates (HIV-1 RNA <50 c/mL) for its
investigational compound, BMS-663068, when compared to a boosted
protease inhibitor, Reyataz® (atazanavir sulfate) with ritonavir.
Among HIV-1 infected treatment-experienced patients receiving
BMS-663068, 69-80% had HIV-1 RNA levels of <50 c/mL (a measure
indicating virus replication is undetectable), compared to 75% of
patients taking Reyataz with ritonavir. Presented at the 21st
Conference on Retroviruses and Opportunistic Infections (CROI) today,
this study highlights the unique mechanism of action of the
investigational prodrug BMS-663068, which when converted into
BMS-626529, a novel attachment inhibitor, prevents initial viral
attachment to the host CD4+ T cell and entry into the host immune cell.
Globally, there are 34 million people who are infected with HIV. Due to
significant scientific advances in management of HIV treatment over the
last 20 years, patients are now living with HIV for a longer period of
time and some patients have developed resistance to existing regimens or
are unable to tolerate current available treatments. Additional
treatment options, especially in new drug classes, are needed both today
and into the future for these patients.
"By targeting the virus at an earlier step of the viral lifecycle,
BMS-663068 disrupts the virus in a way unlike existing antiretroviral
agents," said Jacob P. Lalezari, M.D., director of Quest Clinical
Research and assistant clinical professor of medicine at UCSF/Mount Zion
Hospital. "The data suggest that BMS-663068 is potentially as effective
as one of the current standards of care and may provide another method
of suppressing the virus in treatment-experienced patients who have
failed a prior HIV regimen and need new treatment options."
Study Design and Results
In this active-controlled Phase IIb study, treatment-experienced HIV-1
infected adults (n=254) were randomized equally to one of four
BMS-663068 treatment arms: (400 mg BID (twice daily); 800 mg BID; 600 mg
QD (once daily); 1200 mg QD) and, a control group of Reyataz® (atazanavir
sulfate) and ritonavir (300/100 mg QD). Each treatment arm and the
control group also included raltegravir (RAL) 400 mg BID and tenofovir
disoproxil fumarate (TDF (News - Alert)) 300 mg QD. The primary endpoints were the
proportion of subjects with HIV-1 RNA <50 c/mL at week 24 and the
frequency of serious adverse events (SAEs) and adverse events (AEs)
leading to discontinuation through week 24.
Through week 24, BMS-663068 showed similar efficacy compared to Reyataz
and ritonavir for treatment-experienced patients infected with HIV-1.
Specifically, 69-80% of patients in the four treatment arms had HIV-1
RNA levels <50 c/mL, indicating virus replication was undetectable,
compared to 75% of patients in the control group.
BMS-663068 was generally well-tolerated during the study, with no
serious adverse events attributed to BMS-663068 nor any adverse events
leading to discontinuation. The incidence of Grade 2-4 related AEs
across BMS-663068 arms ranged from 3.9% to 12%, vs. 27.5% in the
comparator arm (atazanavir sulfate and ritonavir) and no causal
association was observed between adverse events and BMS-663068 dose.
"These study results are encouraging and support further development of
BMS-663068 as we continue to look for ways to treat people living with
HIV, especially those who have exhausted available therapies and are
difficult to treat," said Douglas Manion, M.D., senior vice president,
Development, Virology, Bristol-Myers Squibb. "Bristol-Myers Squibb is
committed to the fight against HIV and continues to study treatments
with novel mechanisms of action in hopes of addressing the unmet needs
of both patients recently diagnosed with HIV, treatment-na�ve and
treatment-experienced HIV-infected individuals throughout the world."
About Bristol-Myers Squibb's HIV Research Portfolio
For over 20 years, Bristol-Myers Squibb has focused on discovering,
developing and delivering innovative medicines to help meet the needs of
patients living with HIV/AIDS and continues to pursue advances in
treatment, for both children and adults with HIV. Studies are ongoing
for new treatments including an NRTI (BMS-986001), an attachment
inhibitor prodrug (BMS-663068) and a maturation inhibitor (BMS-955176).
Bristol-Myers Squibb also continues to enhance its current product
offerings for patients living with HIV/AIDS and is developing a
fixed-dose combination of Reyataz® (atazanavir sulfate) and
Gilead's investigational drug cobicistat, which is currently in Phase
III development. New bioequivalence (BE) data
about this combination will also be featured in a poster presentation on
March 6 at 230 p.m. during the 2014 Conference on Retroviruses and
INDICATION and IMPORTANT SAFETY INFORMATION about
REYATAZ (atazanavir sulfate) 200mg/300mg Capsules:
REYATAZ® (atazanavir sulfate) is indicated in combination with other
antiretroviral agents for treatment of�HIV-1 infection. This is based on
analyses of plasma HIV-1 RNA levels and CD4+ cell counts from controlled
studies of 96 weeks (treatment-naive) and 48 weeks
(treatment-experienced) duration in adult and pediatric patients at
least 6 years of age. The following should be considered when initiating
In Study 045, REYATAZ/ritonavir and lopinavir/ritonavir were similar
for the primary efficacy measure of time-averaged difference in change
from baseline in HIV RNA. This study was not large enough to reach a
definitive conclusion that REYATAZ/ritonavir and lopinavir/ritonavir
are equivalent on the secondary efficacy measure of proportions below
the HIV RNA lower limit of detection.
The number of baseline primary protease inhibitor mutations affects
virologic response to REYATAZ/ritonavir.
IMPORTANT SAFETY INFORMATION:
Hypersensitivity: REYATAZ is contraindicated in patients with
previously demonstrated clinically significant hypersensitivity (eg,
Stevens-Johnson syndrome, erythema multiforme, or toxic skin
eruptions) to any of the product components.
Contraindicated Drugs: Coadministration with drugs highly
dependent on CYP3A or UGT1A1 for clearance and for which elevated
plasma concentrations are associated with serious and/or
life-threatening events is contraindicated. These and other
contraindicated drugs are alfuzosin, rifampin, irinotecan, orally
administered midazolam, triazolam, dihydroergotamine, ergotamine,
ergonovine, methylergonovine, cisapride, St. John's wort (Hypericum
perforatum)-containing products, lovastatin, simvastatin,
pimozide, sildenafil dosed as Revatio®, or indinavir.
Drug Interactions: Coadministration with the following drugs is
when REYATAZ is given with ritonavir: nevirapine, boceprevir,
other HIV protease inhibitors, fluticasone propionate.
Voriconazole should not be administered, unless assessment of
benefit/risk justifies its use. Patients should be carefully
monitored for adverse events and loss of efficacy.
when REYATAZ is given without ritonavir: buprenorphine, bosentan,
carbamazepine, phenytoin, phenobarbital.
in treatment-experienced patients: proton-pump inhibitors or
in patients with renal or hepatic impairment: colchicine
See Section 7 (including Table 13), of the Full Prescribing
Information for additional established and other potentially significant
drug interactions, and related dose modification recommendations.
Cardiac Conduction Abnormalities: PR interval prolongation may
occur in some patients. Atrioventricular (AV) conduction abnormalities
were asymptomatic and generally limited to first-degree AV block.
There have been rare reports of second-degree AV block and other
conduction abnormalities. Use REYATAZ with caution in patients with
preexisting conduction system disease or when administered with other
drugs that may prolong the PR interval (including beta-blockers other
than atenolol, diltiazem, verapamil, and digoxin), especially drugs
metabolized by CYP3A. When used with REYATAZ, a 50% dose reduction of
diltiazem should be considered, and ECG monitoring is recommended.
Rash (all grades, generally mild-to-moderate maculopapular skin
eruptions, regardless of causality) occurred in approximately 20% of
patients treated with REYATAZ in controlled clinical trials. Cases of
Stevens-Johnson syndrome, erythema multiforme, and toxic skin
eruptions, including drug rash, eosinophilia and systemic symptoms
(DRESS) syndrome, have been reported. Discontinue REYATAZ if severe
Hyperbilirubinemia: Reversible, asymptomatic elevations in
indirect (unconjugated) bilirubin occurred in most patients treated
with REYATAZ (atazanavir sulfate). There are no long-term safety data
for patients with persistent elevations in total bilirubin >5 times
upper limit of normal. Alternative antiretroviral therapy may be
considered if jaundice or scleral icterus present cosmetic concerns.
Hepatotoxicity: Use REYATAZ with caution in patients with
hepatic impairment because atazanavir concentrations may be increased.
Patients with hepatitis B or C infection or marked elevations in
transaminases are at risk of further transaminase elevations or
hepatic decompensation. In these patients, hepatic laboratory testing
should be performed before and during REYATAZ therapy.
Nephrolithiasis and cholelithiasis have been reported during
postmarketing surveillance in HIV-infected patients receiving REYATAZ.
Some patients required hospitalization and some had complications. If
signs or symptoms of nephrolithiasis and/or cholelithiasis occur,
consider temporary interruption or discontinuation of therapy.
New onset or exacerbation of diabetes mellitus and hyperglycemia have
been reported in patients treated with protease inhibitor therapy. A
causal relationship has not been established.
Immune reconstitution syndrome has been reported in patients
treated with combination antiretroviral therapy, including REYATAZ.
Autoimmune disorders (such as Graves' disease, polymyositis, and
Guillain-Barr� syndrome) have also been reported to occur in the
setting of immune reconstitution; however, the time to onset is more
variable, and can occur many months after initiation of treatment.
Redistribution and/or accumulation of body fat have been seen
in patients receiving antiretroviral therapy. A causal relationship
has not been established.
Increased bleeding has been reported in patients with
hemophilia type A and B treated with protease inhibitors.
Various degrees of cross-resistance among protease inhibitors
have been observed.
The most common moderate or severe adverse reactions were as
follows, regardless of causality:
In treatment-naive adult patients (=2%): nausea
(4-14%), jaundice/scleral icterus (5-7%), rash (3-7%), headache
(1-6%), abdominal pain (4%), vomiting (3-4%), peripheral
neurologic symptoms (<1-4%), diarrhea (1-3%), insomnia (<1-3%),
and dizziness (<1-2%).
In treatment-experienced adult patients (=2%):
jaundice/scleral icterus (9%), myalgia (4%), diarrhea (3%), nausea
(3%), depression (2%), and fever (2%).
In pediatric patients (=5%): cough (21%), fever
(18%), jaundice/scleral icterus (15%), rash (14%), vomiting (12%),
diarrhea (9%), headache (8%), peripheral edema (7%), extremity
pain (6%), nasal congestion (6%), oropharyngeal pain (6%),
wheezing (6%), and rhinorrhea (6%).
REYATAZ should be used with caution in patients with mild to moderate
hepatic impairment. REYATAZ should not be used in patients with severe
hepatic impairment (Child-Pugh Class C). REYATAZ/ritonavir has not
been studied in patients with hepatic impairment and is not
REYATAZ should not be used in treatment-experienced patients with end-stage
renal disease managed with hemodialysis.
Please see accompanying Full Prescribing Information here.
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
or follow us on Twitter (News - Alert) 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 the compounds
mentioned will receive regulatory approval 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, 2013
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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