Bristol-Myers Squibb Submits New Drug Application to U.S. FDA for a Fixed-Dose Combination Tablet of Atazanavir Sulfate with ...
April 14 2014 - 8:00AM
Business Wire
Atazanavir sulfate capsules are available as
Reyataz®
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
been evaluated 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 Vanguard Medical 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 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 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.
Bristol-Myers Squibb CompanyMedia:Carrie FernandezOffice:
609-252-4831; Cell: 215-859-2605carrie.fernandez@bms.comorJulie
FergusonOffice: 609-252-5597; Cell:
312-385-0098julie.ferguson@bms.comorInvestors:Ranya Dajani,
609-252-5330, ranya.dajani@bms.comRyan Asay, 609-252-5020,
ryan.asay@bms.com
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