Bristol-Myers Squibb Submits New Drug Application to U.S. FDA for a
Fixed-Dose Combination Tablet of Atazanavir Sulfate with Cobicistat for
People Living with HIV-1
Atazanavir sulfate capsules are available as Reyataz®
PRINCETON, N.J. -- April 14, 2014
Bristol-Myers Squibb Company (NYSE:BMY) announced today the submission of a
new drug application (NDA) on April 4, 2014 to the U.S. Food and Drug
Administration (FDA) for a fixed-dose combination of atazanavir sulfate, a
protease inhibitor marketed as Reyataz®, and cobicistat, an investigational
pharmacokinetic enhancer, or boosting agent, that can increase the level of
certain HIV-1 medicines in the blood and make them more effective.
Bristol-Myers Squibb is seeking approval of the fixed-dose combination tablet
for use in combination with other antiretroviral agents for the treatment of
HIV-1 infection. If approved, atazanavir sulfate and cobicistat could offer
patients living with HIV-1 a single tablet that eliminates the need to take a
boosting agent in a separate tablet. Cobicistat is being developed by Gilead
Approximately 245,000 patients in the U.S. have been treated with Reyataz
since its launch in 2003, nearly twice that of any other protease inhibitor
launched since that time. Reyataz is currently used in combination with other
antiretroviral agents and is most commonly used with ritonavir, a
pharmacokinetic enhancer. A once-daily therapy, Reyataz is indicated for the
treatment of HIV-1 infection in treatment-naïve and treatment-experienced
adult patients and pediatric patients six years of age or older.
“Bristol-Myers Squibb is committed to enhancing our existing regimens, as well
as developing new therapies to make HIV treatment simpler for patients,” said
Brian Daniels, M.D., senior vice president, Global Development and Medical
Affairs, Bristol-Myers Squibb. “The submission of this NDA represents an
important step forward in our efforts to provide patients with new options for
Reyataz is the only protease inhibitor that has beenevaluated with cobicistat
in a prospective, randomized, Phase III double-blind clinical trial (Gilead’s
Study 114), which compared the efficacy and safety of cobicistat-boosted
Reyataz (atazanavir sulfate) versus ritonavir-boosted Reyataz in
treatment-naïve adult patients for 48 weeks. Study 114 may support the
clinical use of atazanavir and cobicistat together.
“Adhering to HIV treatment regimens can be challenging for some patients, and
if the prescribed medications are not taken properly, it could result in
treatment failure,” said Calvin J. Cohen, M.D., MPH, director of research,
Community Research Initiative of New England and internist, Harvard
VanguardMedical Associates. “If approved by the FDA, a once-daily, fixed-dose
combination of atazanavir sulfate and cobicistat would offer patients living
with HIV-1 another treatment option.”
In October 2011, Bristol-Myers Squibb announced a licensing agreement with
Gilead for the development and commercialization of a once-daily, single
tablet fixed-dose combination product of atazanavir sulfate and Gilead's
cobicistat. Under the terms of the agreement, Bristol-Myers Squibb and its
affiliates are responsible for the formulation, manufacturing, registration,
distribution and commercialization of the atazanavir sulfate and cobicistat
fixed-dose combination product worldwide. Gilead retains sole rights for the
manufacture, development and commercialization of cobicistat as a stand-alone
product and for use in combination with other agents.
About Bristol-Myers Squibb’s HIV Research Portfolio
For more than 20 years, Bristol-Myers Squibb has focused on discovering,
developing and delivering innovative medicines to help meet the needs of
patients living with HIV-1 and continues to pursue advances in treatment, for
both children and adults with HIV-1. Studies are ongoing for new treatments
including an HIV-1 attachment inhibitor (BMS-663068), an HIV-1 maturation
inhibitor (BMS-955176) and an anti-PD-L1 (BMS-936559).
INDICATION and IMPORTANT SAFETY INFORMATION about REYATAZ (atazanavir sulfate)
REYATAZ® (atazanavir sulfate) is indicated in combination with other
antiretroviral agents for treatment ofHIV-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 REYATAZ:
*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
*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 not
*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 (atazanavir sulfate) 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 rash develops.
*Hyperbilirubinemia: Reversible, asymptomatic elevations in indirect
(unconjugated) bilirubin occurred in most patients treated with REYATAZ.
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 (atazanavir sulfate) 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-Barré
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
*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
*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
*REYATAZ (atazanavir sulfate) 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 recommended.
*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 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 the combination
therapy 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.
Bristol-Myers Squibb Company
Office: 609-252-4831; Cell: 215-859-2605
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