New Four- and Five-Year Survival Data for YERVOY® (ipilimumab) in Treatment-Naïve and Previously-Treated Metastatic Melanoma

      New Four- and Five-Year Survival Data for YERVOY® (ipilimumab) in
 Treatment-Naïve and Previously-Treated Metastatic Melanoma Presented at the
          ESMO 2012 Congress (European Society for Medical Oncology)

  PR Newswire

  PRINCETON, New Jersey, September 29, 2012

PRINCETON, New Jersey, September 29, 2012 /PRNewswire/ --

  *Long-Term Follow Up From Phase 3 Study (024) Demonstrated That 19.0
    Percent of Treatment-Naïve Patients Who Received YERVOY at Investigational
    Dose of 10 mg/kg Plus Dacarbazine (DTIC) Were Alive at Four Years vs. 9.6
    Percent of Patients Treated with DTIC Alone
  *Few New Immune-Related Adverse Events Occurred Beyond Two Years of
    Treatment in Study 024 
  *Five-Year Follow Up from Three Exploratory Phase 2 Trials Add to Growing
    Body of Survival Data for YERVOY in Metastatic Melanoma
  *In Both Analyses, Updated Survival Rates Remained Relatively Stable Over
    Time

Bristol-Myers Squibb Company today announced four- and five-year survival
rates based on long-term follow up from Phase 3 and Phase 2 YERVOY ^®
(ipilimumab) clinical trials in patients with treatment-naïve and
previously-treated metastatic melanoma. The data were presented at the ESMO
2012 Congress (European Society for Medical Oncology). (Abstract #1127 and
1116.)

In the Phase 3 trial (024), patients who had not previously received treatment
for metastatic melanoma (n=502) were randomized to receive either the
investigational dose of YERVOY 10 mg/kg in combination with dacarbazine (DTIC,
850 mg/m ^[ ^2 ^] ) or DTIC alone. Long-term follow-up from this study
demonstrated that treatment with YERVOY plus DTIC resulted in a four-year
survival rate of 19.0% compared to 9.6% for DTIC alone. Additionally, the
overall survival data appeared relatively stable between years three and four
for patients treated with YERVOY plus DTIC (21.2% at three years and 19.0% at
four years). The three and four-year survival rates for patients treated with
placebo plus DTIC were 12.1% and 9.6%, respectively.

In three Phase 2 trials (007 [n=115], 008 [n=155] and 022 [n=217]) in which
five-year follow-up data are available through a rollover study (025),
patients received YERVOY at 0.3 mg/kg, 3.0 mg/kg or 10 mg/kg. No comparator
treatment arms were included in these studies. In treatment-naïve patients,
the five-year estimated survival rates ranged from 38% to 49%, which was
unchanged from the four-year rates. In previously-treated patients, the
five-year estimated survival rates (12% to 28%) were relatively stable
compared to the rates at four years (14% to 28%).

For patients who were alive after four years and who continue on therapy in
study 024, few new immune-related adverse events occurred beyond two years of
treatment. Overall safety data from these investigational studies have been
previously presented. ^[1] ^, ^[2] ^, ^[3] ^, ^[4] The types of adverse
events (AEs) attributed to YERVOY in these studies were generally mechanism
(immune)- based.YERVOY can result in severe and fatal immune-related adverse
reactions due to T-cell activation and proliferation. Adverse events
associated with YERVOY were managed with protocol-specific guidelines,
including the administration of systemic corticosteroids, dose
interruption/discontinuation and/or other immunosuppressants.

"Metastatic melanoma is one of the most aggressive forms of cancer with a
historical five-year survival rate of less than ten percent in patients with
distant metastasis. ^[5] Results from these investigational studies showed a
prolonged survival benefit with YERVOY at four and five years for some
patients," said Celeste Lebbe, M.D., Professor of Dermatology, Hôpital
Saint-Louis. "These results add to the growing body of long-term survival data
seen in some patients treated with YERVOY and further our understanding of the
potential of this immunotherapy in the treatment of metastatic melanoma."

About Study 024

Study 024 is a multi-national, randomized, double-blind Phase 3 study that
evaluated the safety and efficacy of YERVOY (10 mg/kg) plus DTIC (850 mg/m ^[
^2 ^] ) vs. DTIC alone in treatment naive patients with Stage III unresectable
or Stage IV metastatic melanoma. Patients who received prior adjuvant therapy
were allowed in the trial. Patients were randomly assigned in a 1:1 ratio to
receive either YERVOY plus DTIC (n=250) or DTIC plus placebo (n=252) at Weeks
1, 4, 7, 10 followed by DTIC alone every 3 weeks through Week 22 (induction
phase). If drug intolerance or progressive disease (PD) was noted during Weeks
12-24, treatment was discontinued. At Week 24, patients who had stable disease
(SD) or an objective response (OR) during induction with no dose-limiting
toxicity could enter a maintenance phase in which they received placebo or
YERVOY every 12 weeks until PD, drug intolerance or end of study. The primary
endpoint of study 024 was overall survival. Results from study 024, which
included three-year follow-up data, were originally published in the New
England Journal of Medicine and presented at the American Society of Clinical
Oncology Annual Meeting in 2011.

The combination of DTIC with YERVOY is not an FDA approved-regimen. In
addition, study 024 was not designed to compare the safety and efficacy of the
FDA-approved monotherapy dose of 3 mg/kg for unresectable or metastatic
melanoma vs. the investigational dose of 10 mg/kg. Bristol-Myers Squibb is
conducting a head-to-head Phase 3 study comparing the safety and efficacy of
the currently-approved dose of 3 mg/kg vs. 10 mg/kg as monotherapy in patients
with previously-treated or treatment naïve unresectable or metastatic
melanoma. This study rapidly accrued patients and completed enrollment in just
over four months.

About Study 025

Study 025 is a rollover Phase 2 study that includes patients from three trials
who only received YERVOY: CA184-008, a single-arm study of YERVOY 10 mg/kg in
previously treated patients (n=155); CA184-022, a dose-ranging study in which
previously treated patients were randomized to receive YERVOY at 0.3 mg/kg
(n=73), 3 mg/kg (n=72), or 10 mg/kg (n=72) with crossover from lower doses to
10 mg/kg allowed in patients whose disease progressed; and CA184-007, a
randomized study of YERVOY 10 mg/kg with or without prophylactic budesonide in
treatment-naïve (n=53) and previously treated patients (n=62). Treatment was
administered every 3 weeks for up to four doses, at which point eligible
patients could receive reinduction or maintenance YERVOY every 12 weeks
starting at week 24. The analysis reported overall survival with updated last
known alive date or death based on data collected through March 2012.

About Metastatic Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of
pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma
is the deadliest form of the disease, and 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 tumors to survive. Melanoma is mostly curable
when treated in its early stages. However, in its late stages, the average
survival rate is just 6 months with a 1-year mortality rate of 75%, making it
one of the most aggressive forms of cancer. These rates are based on a
meta-analysis of 42 Phase 2 trials of more than 2,100 previously-treated and
treatment-naïve patients with Stage IV metastatic melanoma conducted by
multiple cooperative groups from 1975-2005. The incidence of melanoma has been
increasing for at least 30 years. The median age at diagnosis for melanoma is
57 and the median age at death is 67.

About YERVOY

On 25March 2011, the US Food and Drug Administration (FDA) approved ipilimumab
3 mg/kg for the treatment of patients with unresectable (inoperable) or
metastatic melanoma in the US. On 13 July 2011, the EU approved ipilimumab 3
mg/kg for the treatment of adult patients with previously-treated unresectable
or metastatic melanoma.

YERVOY, which is a recombinant, human monoclonal antibody, is the first
FDA-approved cancer immunotherapy that blocks the cytotoxic T- lymphocyte
antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell
activation.Ipilimumab 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 ipilimumab's
effect in patients with melanoma is indirect, possibly through T-cell mediated
anti-tumor immune responses.

For full Prescribing Information, please refer to the SMPC.

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. Weber J, Thompson JA, Hamid O, et al. A randomized, double-blind,
placebo-controlled, phase II study comparing the tolerability and efficacy of
ipilimumab administered with or without prophylactic budesonide in patients
with unresectable stage III or IV melanoma. Clin Cancer Res 2009;15:5591-5598.

2. Wolchok JD, Neyns B, Linette G, et al. Ipilimumab monotherapy in patients
with pretreated advanced melanoma: a randomised, double-blind, multicentre,
phase 2, dose-ranging study. Lancet Oncol 2010;11:155-164.

3. O'Day SJ, Maio M, Chiarion-Sileni V, et al. Efficacy and safety of
ipilimumab monotherapy in patients with pretreated advanced melanoma: a
multicentre, single-arm, phase II study. Ann Oncol 2010;21:1712-1717.

4. Thomas L, Wolchok JD, Garbe C, et al. Safety of ipilimumab in patients
(pts) with untreated, advanced melanoma alive beyond 2 years: Results from a
phase III study. J Clin Oncol. 2012;30(15s): abstract 8512. 

5. National Comprehensive Cancer Network (NCCN) Web site. "NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines): Melanoma." Available at:
http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf  Accessed
on September 19, 2012.

Contact: Media: Elzbieta Zawislak, +33-615523580 elzbieta.zawislak@bms.com ;
Investors: John Elicker, +1-609-252-4611, john.elicker@bms.com
 
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