PRINCETON, N.J., Oct. 16 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb
Company (NYSE: BMY) announced today that the U.S. Food and Drug
Administration (FDA) has granted approval of IXEMPRA(TM) (ixabepilone) as
monotherapy for the treatment of patients with metastatic or locally
advanced breast cancer in patients whose tumors are resistant or refractory
to anthracyclines, taxanes, and capecitabine. The FDA has also granted
approval of IXEMPRA in combination with capecitabine for the treatment of
patients with metastatic or locally advanced breast cancer resistant to
treatment with an anthracycline, and a taxane, or whose cancer is taxane
resistant and for whom further anthracycline therapy is contraindicated.
IXEMPRA is a microtubule inhibitor belonging to a class of antineoplastic
agents, the epothilones. Bristol-Myers Squibb anticipates that IXEMPRA will
be available within days.
"Previously, patients with aggressive metastatic or locally advanced
breast cancer no longer responding to currently available chemotherapies
had limited treatment options," said Linda Vahdat, M.D., Associate
Professor of Clinical Medicine and Associate Attending Physician, New
York-Presbyterian Hospital/Weill Cornell Medical Center. "The approval of
IXEMPRA means that we now have an important new option for patients with
metastatic breast cancer who have rapidly progressed through currently
approved chemotherapies."
"Bristol-Myers Squibb has a rich history in oncology spanning more than
40 years, and we are extremely proud that IXEMPRA has been approved as it
is a significant addition to the Bristol-Myers Squibb oncology portfolio
and addresses a serious unmet medical need in the treatment of patients
with metastatic or locally advanced breast cancer," said Elliott Sigal,
M.D., Ph.D., Executive Vice President, Chief Scientific Officer and
President, Research and Development, Bristol-Myers Squibb.
Registrational Trials
The FDA reviewed the efficacy and safety of IXEMPRA based on the
analysis of two multi-center, multinational trials that included 878
patients and evaluated IXEMPRA either as a monotherapy or in combination
with capecitabine in patients with metastatic or locally advanced breast
cancer.
(Phase II, Monotherapy Trial: -081) The single-arm Phase II trial
evaluated the efficacy and safety of IXEMPRA as a monotherapy. This study
enrolled 126 patients with metastatic or locally advanced breast cancer
resistant to three prior therapies (an anthracycline, a taxane and
capecitabine). Resistance was defined as disease progression while on
therapy in the metastatic setting (defined as progression while on
treatment or within eight weeks of last dose) or recurrence within six
months of the last dose in the adjuvant or neoadjuvant setting (only for
anthracycline and taxane). HER2 positive patients must also have progressed
during or after discontinuation of trastuzumab. The primary endpoint was
objective response rate, which is an assessment of tumor shrinkage in
response to treatment. Results determined by an independent radiology
review (IRR) showed an objective partial response of 12.4% (95% CI,
6.9-19.9) in 113 response-evaluable patients.
Treatment-related non-hematological adverse events (greater than or
equal to 20%) included: peripheral sensory neuropathy 62% (Grade 3/4: 14%),
fatigue/asthenia 56% (Grade 3/4: 13%), myalgia/arthralgia 49% (Grade 3/4:
8%), alopecia 48% (Grade 3/4: 0%), nausea 42% (Grade 3/4: 2%),
stomatitis/mucositis 29% (Grade 3/4: 6%), vomiting 29% (Grade 3/4: 1%),
diarrhea 22% (Grade 3/4: 1%), and musculoskeletal pain 20% (Grade 3/4: 3%).
Treatment-related hematological adverse events (greater than or equal to
20%) included: neutropenia (Grade 3/4: 54%) and leukopenia (Grade 3/4:
49%).
(Phase III, Combination Trial: -046) The randomized Phase III trial
evaluated the efficacy and safety of IXEMPRA in combination with
capecitabine in comparison with capecitabine as monotherapy. This trial
included 752 patients who were previously treated with anthracyclines and
taxanes, and whose tumors had demonstrated prior resistance to these
therapies. Anthracycline resistance is defined as progression while on
therapy or within six months in the adjuvant setting, or three months in
the metastatic setting. Taxane resistance is defined as progression while
on therapy or within 12 months in the adjuvant setting or four months in
the metastatic setting. Evaluation of the primary endpoint demonstrated
that IXEMPRA in combination with capecitabine resulted in a statistically
significant improvement in progression-free survival compared to
capecitabine monotherapy - median 5.7 (95% CI, 4.8-6.7) vs. 4.1 months (95%
CI, 3.1-4.3); P<0.0001, Hazard ratio=0.69 (95% CI, 0.58-0.83).
Treatment-related non-hematological adverse events (greater than or
equal to 20%) reported in patients treated with IXEMPRA in combination with
capecitabine included: peripheral sensory neuropathy 65% (Grade 3/4: 21%),
palmar-plantar erythrodysesthesia (hand-foot) syndrome 64% (Grade 3/4:
18%), fatigue/asthenia 60% (Grade 3/4: 16%), nausea 53% (Grade 3/4: 3%),
diarrhea 44% (Grade 3/4: 6%), vomiting 39% (Grade 3/4: 4%),
myalgia/arthralgia 39% (Grade 3/4: 8%), anorexia 34% (Grade 3/4: 3%),
stomatitis/mucositis 31% (Grade 3/4: 4%), alopecia 31% (Grade 3/4: 0%),
abdominal pain 24% (Grade 3/4: 2%), nail disorder 24% (Grade 3/4: 2%),
musculoskeletal pain 23% (Grade 3/4: 2%), and constipation 22% (Grade 3/4:
0%). Treatment-related hematological adverse events (greater than or equal
to 20%) reported in patients treated with IXEMPRA in combination with
capecitabine included: neutropenia (Grade 3/4: 68%) and leukopenia (Grade
3/4: 57%).
Comparative treatment-related non-hematological adverse events reported
in patients treated with capecitabine alone included: peripheral sensory
neuropathy 16% (Grade 3/4: 0%), palmar-plantar erythrodysesthesia
(hand-foot syndrome) 63% (Grade 3/4: 17%), fatigue/asthenia 29% (Grade 3/4:
4%), nausea 40% (Grade 3/4: 2%), diarrhea 39% (Grade 3/4: 9%), vomiting 24%
(Grade 3/4: 2%), myalgia/arthralgia 5% (Grade 3/4: <1%), anorexia 15%
(Grade 3/4: 1%), stomatitis/mucositis 20% (Grade 3/4: 3%), alopecia 3%
(Grade 3/4: 0%), abdominal pain 14% (Grade 3/4: 1%), nail disorder 10%
(Grade 3/4: <1%), musculoskeletal pain 5% (Grade 3/4: 0%), and constipation
6% (Grade 3/4: <1%). Treatment-related hematological adverse events of
Grade 3/4 severity reported in patients treated with capecitabine alone
included: neutropenia 11% and leukopenia 6%.
IMPORTANT SAFETY INFORMATION
TOXICITY IN HEPATIC IMPAIRMENT
IXEMPRA (ixabepilone) in combination with capecitabine is
contraindicated in patients with AST or ALT >2.5 x ULN or bilirubin >1 x
ULN due to increased risk of toxicity and neutropenia-related death.
In combination with capecitabine, the overall frequency of Grade 3/4
adverse reactions, febrile neutropenia, serious adverse reactions, and
toxicity related deaths was greater in patients with hepatic impairment.
Caution should be used when using IXEMPRA as monotherapy in patients
with AST or ALT > 5 x ULN. Use of IXEMPRA in patients with AST or ALT > 10
x ULN or bilirubin >3 x ULN is not recommended.
With monotherapy, Grade 4 neutropenia, febrile neutropenia, and serious
adverse reactions were more frequent in patients with hepatic impairment.
CONTRAINDICATIONS
IXEMPRA is contraindicated in patients:
* with a known history of a severe (CTC Grade 3/4) hypersensitivity
reaction to agents containing Cremophor(R) EL or its derivatives such as
polyoxyethylated castor oil.
* who have a baseline neutrophil count <1500 cells/mm(3) or a platelet
count <100,000 cells/mm(3).
HYPERSENSITIVITY REACTION
Premedicate with an H1 and an H2 antagonist approximately 1 hour before
IXEMPRA infusion and observe for hypersensitivity reactions (e.g.,
flushing, rash, dyspnea, and bronchospasm).
In case of severe hypersensitivity reactions, infusion of IXEMPRA
should be stopped and aggressive supportive treatment (e.g., epinephrine,
corticosteroids) started.
Patients who experience a hypersensitivity reaction in one cycle of
IXEMPRA must be premedicated in subsequent cycles with a corticosteroid in
addition to the H1 and H2 antagonists, and extension of the infusion time
should be considered.
MYELOSUPPRESSION
Patients should be monitored for myelosuppression; frequent peripheral
blood cell counts are recommended for all patients receiving IXEMPRA.
Patients who experience severe neutropenia or thrombocytopenia should
have their dose reduced. Neutropenia related deaths occurred in patients
administered IXEMPRA and capecitabine (1.9% of 414 patients) and IXEMPRA
alone (0.4% in 240 patients).
PERIPHERAL NEUROPATHY
Patients treated with IXEMPRA should be monitored for symptoms of
neuropathy, such as burning sensation, hyperesthesia, hypoesthesia,
paresthesia, discomfort, or neuropathic pain. Patients experiencing new or
worsening peripheral neuropathy may require changes in the dose or
discontinuation of IXEMPRA. Neuropathy was the most frequent cause of
treatment discontinuation due to drug toxicity. Caution should be used when
treating patients with diabetes mellitus or existing moderate to severe
neuropathy.
PREGNANCY
Women should be advised not to become pregnant when taking IXEMPRA. If
this drug is used during pregnancy or the patient becomes pregnant, the
patient should be apprised of the potential hazard to the fetus.
CARDIAC ADVERSE REACTIONS
Caution should be exercised in patients with a history of cardiac
disease. Discontinuation of IXEMPRA should be considered in patients who
develop cardiac ischemia or impaired cardiac function due to reports of
cardiovascular adverse reactions (e.g., myocardial ischemia,
superventricular arrhythmia, and ventricular dysfunction). The frequency of
cardiac adverse reactions (myocardial ischemia and ventricular dysfunction)
was higher in the IXEMPRA in combination with capecitabine (1.9%) than in
the capecitabine alone (0.3%) treatment group.
POTENTIAL FOR COGNITIVE IMPAIRMENT FROM EXCIPIENTS
IXEMPRA contains dehydrated alcohol USP. Consideration should be given
to the possibility of central nervous system and other effects of alcohol.
ADVERSE REACTIONS
The most common adverse reactions (greater than or equal to 20%)
reported by patients receiving IXEMPRA were peripheral sensory neuropathy,
fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting,
stomatitis/mucositis, diarrhea, and musculoskeletal pain. The following
additional events occurred in greater than or equal to 20% in combination
treatment: palmar-plantar erythrodysesthesia (hand-foot) syndrome,
anorexia, abdominal pain, nail disorder, and constipation. Drug-associated
hematologic abnormalities (>40%) include neutropenia, leukopenia, anemia,
and thrombocytopenia.
About Bristol-Myers Squibb
For more than 40 years, Bristol-Myers Squibb has been committed to
building a unified vision for the future of cancer treatment. With
expertise, dedication and resolve, that vision led to the development of a
diverse global portfolio of anti-cancer therapies that are an important
cornerstone of care today. Hundreds of scientists in Bristol-Myers Squibb's
Research & Development organization are studying ways to improve current
cancer treatments and identify better, more effective medicines for the
future. Bristol-Myers Squibb is a global pharmaceutical and related health
care products company whose mission is to extend and enhance human life.
For more information regarding IXEMPRA, please call 1-888-IXEMPRA
(1-888-493-6772) Monday through Friday 8:00 am-5:00 pm ET or visit
http://www.IXEMPRA.com.
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995. 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
as to when IXEMPRA (ixabepilone) will be commercially available.
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, 2006 and in our Quarterly Reports on Form 10-Q.
Bristol-Myers Squibb undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information, future
events or otherwise.
SOURCE Bristol-Myers Squibb Company
 back to top
Related links:
http://www.bms.com
http://www.IXEMPRA.com
CONTACT:
Media, Madeline Malia, Communications,
+1-609-252-3347, or mobile, +1-609-651-1323,
madeline.malia@bms.com, or Tony Plohoros, Communications,
+1-609-252-7938, or +1-212-546-4379, or mobile, +1-908-591-2839,
tony.plohoros@bms.com, or investors, John Elicker, Investor
Relations, +1-212-546-3375, john.elicker@bms.com, all of
Bristol-Myers Squibb
|
