YERVOY? (ipilimumab) Approved for the Treatment of Previously-Treated Advanced Melanoma in the EU

Paris (ots/PRNewswire) -

- First and Only Approved Therapy for Pre-treated Unresectable
or Metastatic Melanoma to Demonstrate a Significant Improvement in
Overall Survival
- First EU-Approved Therapy for Pre-treated Unresectable or
Metastatic Melanoma in More Than Two Decades

Bristol-Myers Squibb today announced that the European Commission
has approved YERVOY(TM) (ipilimumab) for the treatment of adult
patients with previously-treated advanced melanoma.

YERVOY, an innovative immunotherapy, showed long-term survival in
the treatment of patients with advanced melanoma in a randomised,
double-blind Phase III study published in the New England Journal of
Medicine in June 2010.[1] Based on the survival (Kaplan-Meier) curve,
the 1 and 2-year estimated survival rates for patients treated with
YERVOY were 46% and 24% respectively vs. 25% and 14% in the
comparator arm with some patients alive at 3 and 4 years.

"With the approval of YERVOY physicians now have an important new
option to offer to patients with metastatic melanoma. This is a
chance of not just months but potentially 3 to 4 years of prolonged
survival for some patients in the treatment of metastatic melanoma,"
comments Professor Alexander Eggermont, General Director, Institut
Gustave Roussy, Paris, France. "There is hope that YERVOY's novel
mode of action, together with the fact that the recommended complete
course of treatment with YERVOY (3 mg/kg) includes 4 infusions over 3
months, could potentially change the way we treat patients with
previously treated advanced melanoma. It is an example of what can be
done through unleashing the power of one's own immune response."

Bristol-Myers Squibb will now work closely with local health
authorities to expedite the availability of YERVOY across the
European Union. Prior to approval, the Company provided ipilimumab to
nearly 3,000 patients throughout Europe through Compassionate Use /
Named Patient Programmes. The Company remains committed to helping
ensure that appropriate patients who need YERVOY will receive it
while the reimbursement process is finalised by the relevant
authorities throughout Europe.

Ron Cooper, President Bristol-Myers Squibb Europe, stated:"With
an average survival time on diagnosis of 6-9 months, patients with
advanced melanoma have had little hope - until now. The European
Union approval of YERVOY is a milestone for patients with advanced
disease and is the first outcome of Bristol-Myers Squibb's commitment
to immuno-oncology. Through the Bristol-Myers Squibb String of Pearls
strategy, we began a collaboration with Medarex, acquired the company
and developed YERVOY. We will continue this strategy to seek and
establish collaborations with other leading innovators across the
globe. Through these and other initiatives we work towards our single
mission: to discover, develop and deliver innovative medicines that
help patients prevail over serious diseases."

YERVOY represents a new treatment paradigm in the evolving
discipline of immuno-oncology. It indirectly targets the tumour by
stimulating the patient's immune system to recognise and destroy
cancer cells.[2] YERVOY specifically blocks cytotoxic T lymphocyte
antigen 4 (CTL4), which plays a role in suppressing the normal immune
response. YERVOY blocks that suppression to allow the immune system
to respond to melanoma cancer cells.

The types of adverse events (AEs) attributed to YERVOY are
generally mechanism (immune)-based. YERVOY can result in severe and
fatal immune-related adverse reactions due to T-cell activation and
proliferation. These immune-mediated reactions may involve any organ
system; however, the most common severe immune-mediated adverse
reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority
of these immune-mediated reactions initially manifested during
treatment; however, a minority occurred weeks to months after
discontinuation of YERVOY. Patients should be assessed for signs and
symptoms of enterocolitis, dermatitis, neuropathy and endocrinopathy
and clinical chemistries should be evaluated, including liver
function tests and thyroid function tests, at baseline and before
each dose.

Adverse events associated with YERVOY are managed with
protocol-specific guidelines, including the administration of
systemic corticosteroids, dose interruption/discontinuation and/or
other immunosuppressants.

About Advanced Melanoma

Melanoma is a form of skin cancer characterised by the
uncontrolled growth of pigment-producing cells (melanocytes) located
in the skin.[3] Advanced melanoma occurs when cancer spreads beyond
the surface of the skin to other organs, such as the lymph nodes,
lungs, brain or other areas of the body. Some cancer cells can
actively evade surveillance by the immune system, allowing tumours to
survive.

Melanoma is mostly curable when treated in its early stages.[4]
However, metastatic melanoma is one of the most aggressive forms of
cancer with 75% of people dying within one year.[5] Due to the very
poor prognosis and lack of effective treatments for patients with
stage III unresectable and stage IV metastatic melanoma, there
remains a significant unmet medical need.

Unlike most other solid tumours, melanoma affects younger, middle
aged people. The median age at diagnosis for melanoma is 57 and the
median age at death is 67.[6]

About YERVOY (ipilimumab)

YERVOY, which is a recombinant, human monoclonal antibody, blocks
the cytotoxic T- lymphocyte antigen-4 (CTLA-4). CTLA-4 is a negative
regulator of T-cell activation. YERVOY binds to CTLA-4 and blocks the
interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4
has been shown to augment T-cell activation and proliferation. The
mechanism of action of YERVOY's effect in patients with melanoma is
indirect, possibly through T-cell mediated anti-tumour immune
responses.

On 25th March 2011, the US Food and Drug Administration (FDA)
approved YERVOY 3 mg/kg for the treatment of patients with
unresectable (inoperable) or metastatic melanoma in the US.

About the Reference Data - MDX010-020 Study: Improved Survival
with Ipilimumab in Patients with Pre-Treated Metastatic Melanoma

The approval is based on a Phase 3, double-blind study that
randomized 676 patients with unresectable or metastatic melanoma who
were previously treated with one or more of the following:
aldesleukin, dacarbazine, temozolomide, fotemustine, or
carboplatin.Patients were randomized in a 3:1:1 ratio to receive
either YERVOY (ipilimumab) (3mg/kg) in combination with the
investigational peptide vaccine gp100 (n=403), YERVOY alone (3mg/kg;
n=137), or gp100 alone (n=136).

The primary endpoint of the pivotal Phase 3 study was overall
survival in the YERVOY plus gp100 arm vs. the gp100 arm. Secondary
efficacy endpoints included overall survival in the YERVOY plus gp100
arm vs. the YERVOY arm, overall survival in the YERVOY arm vs. the
gp100 arm, Best Overall Response Rate ("BORR") at week 24 and
duration of response.

Patients received YERVOY (3mg/kg) as an intravenous infusion
administered over 90 minutes every 3 weeks for four doses. Assessment
of tumor response to YERVOY was conducted at weeks 12 and 24, and
every 3 months thereafter. Patients with evidence of objective tumor
response at 12 or 24 weeks had assessment for confirmation of
durability of response at 16 or 28 weeks, respectively. Between 57%
and 64% of patients treated in each study arm received all four
planned doses.

YERVOY was studied in patients with a typically poor prognosis,
including those with brain metastases, elevated LDH, and visceral
disease (M1c). In the study, 71% had M1c stage, 12% had a history of
previously-treated brain metastasis, 98% had ECOG performance status
of 0 and 1, 23% had received aldeskeukin and 38% had elevated LDH
level. Additionally, 29% of patients were 65 years or older with a
median age of 57 years.The median duration of follow-up was 8.9
months.

Kaplan-Meier estimated survival rate at 1 year was 46% (95% CI:
37.0, 54.1) in the YERVOY armvs. 25% (95% CI: 18.1, 32.9) in the
gp100 arm. The estimated survival rate at 2 years was 24% (95% CI:
16.0, 31.5) in the YERVOY arm vs. 14%[2] (95% CI: 8.0, 20.0) in the
gp100 arm. Patients treated with YERVOY had a 34% reduction in the
risk of death over the gp100 control arm (HR = 0.66 [95% CI:
0.51-0.87], P=0.0026). Patients treated with YERVOY (ipilimumab) plus
gp100 had a 32% reduction in the risk of death over the gp100 control
arm (HR = 0.68 [95% CI: 0.55-0.85], P=0.0004). Median overall
survival was 10 (95% CI: 8.0-13.8), 10 (95% CI: 8.5-11.5) and 6 (95%
CI: 5.5-8.7) months for the YERVOY alone, YERVOY + gp100 arm and
gp100 alone arms, respectively.

In patients who received 3 mg/kg YERVOY alone (n=131), severe to
fatal immune-related adverse reactions were reported and included
enterocolitis (7%), endocrinopathy (4%, all of which had
hypopituitarism), dermatitis (2%), hepatitis (1%), neuropathy (1%),
nephritis (1%), and eosinophilia (1%).In patients who received 3
mg/kg of YERVOY + gp100 (n=380) severe to fatal immune-related
adverse reactions were reported and included enterocolitis (7%),
hepototoxicity (2%), dermatitis (3%), endocrinopathy (1%,
hypopituitarism, 1% adrenal insufficiency), pneumonitis (<1%),
meningitis (<1%), pericarditis (<1%).The most common adverse
reactions were fatigue (41%), diarrhoea (32%), pruritus (31%), rash
(29%) and colitis (8%) for the YERVOY alone arm, diarrhoea (37%),
fatigue (34%), rash (25%), pruritus (21%), and colitis (5%) for the
YERVOY +gp100 arm, and fatigue (31%), diarrhoea (20%), pruritus
(11%), rash (8%), and colitis (2%) for gp100 arm. YERVOY therapy was
discontinued for adverse reactions in 10% of patients.

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.

This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding product development. 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 product described in this release will become commercially
successful. 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, 2010, 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.

1. Hodi FS et al. Improved Survival with Ipilimumab in Patients
with Metastatic Melanoma. N Engl J Med 2010;363(8):711-23.

2. Weber J. Review: anti-CTLA-4 antibody ipilimumab: case studies
of clinical response and immune related adverse events. Oncologist
2007;12:864-72.

3. Skin Cancer Foundation. What is melanoma? Available at
http://www.skincancer.org/Melanoma. Accessed July 2011.

4. American Cancer Society. Melanoma skin cancer. Can melanoma be
found early? Available at http://www.cancer.org/cancer/skincancer-mel
anoma/detailedguide/melanoma-skin -cancer-detection. Accessed July
2011.

5. Korn E et al. Meta-analysis of phase 2 cooperative group
trials in metastatic stage IV melanoma to determine progression-free
and overall survival benchmarks for future phase 2 trials. J Clin
Oncol 2008;26:527-534.

6. Markovic SN et al. Malignant melanoma in the 21st century,
part 1: epidemiology, risk factors, screening, prevention, and
diagnosis. Mayo Clin Proc. 2007;82:364-380.

ots Originaltext: Bristol-Myers Squibb GmbH & Co.KG aA
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Media Contact: Elzbieta Zawislak,
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