Bristol-Myers Squibb Submits New Drug Application to U.S. FDA for a Fixed-Dose Combination Tablet of Atazanavir Sulfate with

  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®

Business Wire

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
Sciences, Inc.

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 treatment.”

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)
200mg/300mg Capsules:

INDICATION:

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
    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 not
    recommended.

       *nevirapine, salmeterol
       *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
         efavirenz
       *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
    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 (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.

Contact:

Bristol-Myers Squibb Company
Media:
Carrie Fernandez
Office: 609-252-4831; Cell: 215-859-2605
carrie.fernandez@bms.com
or
Julie Ferguson
Office: 609-252-5597; Cell: 312-385-0098
julie.ferguson@bms.com
or
Investors:
Ranya Dajani, 609-252-5330, ranya.dajani@bms.com
Ryan Asay, 609-252-5020, ryan.asay@bms.com
 
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