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Bristol-Myers Squibb's ORENCIA (abatacept) Receives FDA Approval for Treatment of Active Psoriatic Arthritis (PsA) in Adults

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Bristol-Myers
Squibb Company
(NYSE:BMY) announced today the U.S. Food and Drug
Administration (FDA) has approved ORENCIA for the treatment of adults
with active Psoriatic Arthritis (PsA)1, a chronic2,
inflammatory disease that can affect both the skin and musculoskeletal
system.3 ORENCIA is approved and available in both
intravenous and subcutaneous (SC) injection formulations.1
ORENCIA should not be administered concomitantly with TNF antagonists,
and is not recommended for use concomitantly with other biologic
Rheumatoid Arthritis (RA) therapy, such as anakinra.1 This
approval marks the third autoimmune disease indication for ORENCIA.1

"This approval underscores the efficacy of ORENCIA in adult patients
with active Psoriatic Arthritis, who have been in need of new
treatments," said Brian J. Gavin, Vice President, ORENCIA Development
Lead at Bristol-Myers Squibb. "Helping to advance clinical understanding
of autoimmune conditions is a key focus of our immunoscience research,
and we're proud to introduce ORENCIA, a selective T-cell co-stimulation
modulator, as an additional treatment option for PsA."

The co-stimulation blockade of ORENCIA inhibits T-cell activation and
the resulting cascade of events that contribute to inflammation. T-cell
activation is involved in the pathogenesis of PsA.4

Psoriatic Arthritis can cause joint pain, stiffness and reduced range of
motion3, potentially affecting the ability to do everyday
activities, such as getting dressed and tying shoes.3,5 In
PsA, the immune system attacks healthy joints and skin.6

"Psoriatic Arthritis takes a toll on patients and families over time,7"
said Randy Beranek, president and CEO, National Psoriasis Foundation.
"We welcome the introduction of an additional treatment option for
adults with active Psoriatic Arthritis, because we believe advancements,
along with further research, education and support services, are
critical to helping improve the lives of those impacted."

The approval was based on results from two randomized, double-blind,
placebo-controlled trials in which ORENCIA improved (or reduced) disease
activity in both TNF-naive and exposed patients with high disease
activity, high tender and swollen joints, and a disease duration of more
than seven years.1,4,8

ORENCIA PsA IV and SC Studies Demonstrated
Improved Disease Response

The efficacy of ORENCIA was assessed in two randomized, double-blind,
placebo-controlled studies (Studies PsA-I and PsA-II) in 594 adult
patients with disease duration more than seven years. Patients had
active Psoriatic Arthritis (≥ 3 swollen joints and ≥ 3 tender joints)
despite prior treatment with DMARD therapy and had one qualifying
psoriatic skin lesion of at least 2 cm in diameter. In PsA-I and PsA-II,
37% and 61% of patients, respectively, were treated with TNF inhibitors
(TNFi) previously.1 The primary endpoint for both PsA-I and
PsA-II was the proportion of patients achieving ACR 20 response at Week
24 (Day 169).1

In PsA-I, a dose-ranging study, 170 patients received study drug IV at
Days 1, 15, 29, and then every 28 days thereafter in a double-blind
manner for 24 weeks, followed by open-label ORENCIA every 28 days.
Patients were randomized to receive placebo or ORENCIA 3 mg/kg, 10 mg/kg
(weight range-based dosing: 500 mg for patients weighing less than 60
kg, 750 mg for patients weighing 60 to 100 kg, and 1000 mg for patients
weighing greater than 100 kg), or two doses of 30 mg/kg followed by
weight range-based dosing of 10 mg/kg without escape for 24 weeks.
Patients were allowed to receive stable doses of concomitant
methotrexate, low dose corticosteroids (equivalent to ≤ 10 mg of
prednisone) and/or NSAIDs during the trial. At enrollment, approximately
60% of patients were receiving methotrexate.1

In PsA-II, 424 patients were randomized 1:1 to receive weekly doses of
SC placebo or ORENCIA 125 mg SC without a loading dose for 24 weeks,
followed by open-label ORENCIA 125 mg SC weekly. Patients were allowed
to receive stable doses of concomitant methotrexate, sulfasalazine,
leflunomide, hydroxychloroquine, low dose corticosteroids (equivalent to
≤ 10 mg of prednisone) and/or NSAIDs during the trial. At randomization,
60.4% of patients were receiving methotrexate.1

A higher proportion of patients treated with ORENCIA 10 mg/kg IV or 125
mg SC achieved an ACR20 response at Week 24 compared to placebo, 47.5%
versus 19.0% and 39.4% versus 22.3% (p< 0.05), respectively.1
Responses were seen regardless of prior anti-TNFi treatment and
regardless of concomitant non-biologic DMARD treatment.1
Improvements in enthesitis and dactylitis were seen with ORENCIA
treatment at Week 24 in both IV and SC.1

There was a higher proportion of ORENCIA IV patients with at least a
0.30 decrease from baseline in Health Assessment
Questionnaire-Disability Index (HAQ-DI) score at Week 24, with an
estimated difference for ORENCIA 10 mg/kg (weight range-based dosing as
described above) (45.0%) vs. placebo (19.0%) of 26.1 (95% confidence
interval: 6.8, 45.5).1 The proportion of ORENCIA SC patients
with at least a 0.35 decrease from baseline in HAQ-DI on ORENCIA was
31%, as compared to 24% on placebo (estimated difference: 7%; 95%
confidence interval: -1%, 16%).1 There was a higher adjusted
mean change from baseline in HAQ-DI on ORENCIA SC (-0.33) vs. placebo
(-0.20) at Week 24, with an estimated difference of -0.13 (95%
confidence interval: -0.25, -0.01). 1

The safety profile of ORENCIA was comparable between studies PsA-I and
PsA-II and consistent with the safety profile in RA. The most serious
adverse reactions reported in studies of adult RA patients were serious
infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA
vs 1.1% placebo). Headache, upper respiratory tract infection,
nasopharyngitis, and nausea were the most commonly reported adverse
events (≥ 10%) in the adult RA clinical studies. In PsA-II, the most
common adverse reactions (≥ 5%) were nasopharyngitis, upper respiratory
tract infection, and bronchitis.

"It can be difficult to treat active Psoriatic Arthritis patients
because the disease course is unpredictable, and patients are often
treated with a variety of medications such as classic DMARDs and TNFs
over time.4 Furthermore, once they have been treated, it may
be more difficult to obtain an adequate efficacy response," said Philip
Mease, M.D., Clinical Professor at the University of Washington School
of Medicine and Director of the Rheumatology Clinical Research Division
of Swedish Medical Center. "The data that formed the basis of this
approval demonstrate that ORENCIA offers an additional treatment option
for patients with active Psoriatic Arthritis who have already tried a
TNF inhibitor, as well as those who have not."

About Psoriatic Arthritis

Psoriatic arthritis (PsA) is a chronic2, inflammatory disease
that can affect both the skin and musculoskeletal system.3 PsA
can cause joint pain, stiffness and reduced range of motion.3
Most commonly affecting the distal joints (those closest to the nail) of
the fingers or toes, as well as the wrists, knees, ankles and lower
back, the disease usually appears between the ages of 30 to 50, but can
begin as early as childhood.3 Men and women are equally at
risk.3 Early recognition, diagnosis and treatment of
Psoriatic Arthritis are critical to helping relieve pain and
inflammation.3

Indication and Important Safety Information for ORENCIA®
(abatacept)

Indication and Usage

Adult Rheumatoid Arthritis (RA): ORENCIA® (abatacept) is
indicated for reducing signs and symptoms, inducing major clinical
response, inhibiting the progression of structural damage, and improving
physical function in adult patients with moderately to severely active
RA. ORENCIA may be used as monotherapy or concomitantly with
disease-modifying, anti-rheumatic drugs (DMARDs) other than tumor
necrosis factor (TNF) antagonists.

Juvenile Idiopathic Arthritis (JIA): ORENCIA® (abatacept) is
indicated for reducing signs and symptoms in patients 2 years of age and
older with moderately to severely active polyarticular JIA. ORENCIA may
be used as monotherapy or concomitantly with methotrexate (MTX).

Adult Psoriatic Arthritis (PsA): ORENCIA® (abatacept)
is indicated for the treatment of adult patients with active PsA.

Important Limitations of Use: ORENCIA should not be administered
concomitantly with TNF antagonists, and is not recommended for use
concomitantly with other biologic RA therapy, such as anakinra.

Important Safety Information for ORENCIA® (abatacept)

Concomitant Use with TNF Antagonists: Concurrent therapy with
ORENCIA and a TNF antagonist is not recommended. In controlled clinical
trials, adult RA patients receiving concomitant intravenous ORENCIA and
TNF antagonist therapy experienced more infections (63%) and serious
infections (4.4%) compared to patients treated with only TNF antagonists
(43% and 0.8%, respectively), without an important enhancement of
efficacy.

Hypersensitivity: Anaphylaxis or anaphylactoid reactions can
occur during or after an infusion and can be life-threatening. There
were 2 cases (<0.1%; n=2688) of anaphylaxis or anaphylactoid reactions
in clinical trials with adult RA patients treated with intravenous
ORENCIA. Other reactions potentially associated with drug
hypersensitivity, such as hypotension, urticaria, and dyspnea, each
occurred in <0.9% of patients. There was one case of a hypersensitivity
reaction with ORENCIA in JIA clinical trials (0.5%; n=190). In
postmarketing experience, a case of fatal anaphylaxis following the
first infusion of ORENCIA was reported. Appropriate medical support
measures for treating hypersensitivity reactions should be available for
immediate use. If an anaphylactic or other serious allergic reaction
occurs, administration of ORENCIA should be stopped immediately and
permanently discontinued, with appropriate therapy instituted.

Infections: Serious infections, including sepsis and pneumonia,
have been reported in patients receiving ORENCIA. Some of these
infections have been fatal. Many of the serious infections have occurred
in patients on concomitant immunosuppressive therapy which, in addition
to their underlying disease, could further predispose them to infection.
Caution should be exercised in patients with a history of infection or
underlying conditions which may predispose them to infections. Treatment
with ORENCIA should be discontinued if a patient develops a serious
infection. Patients should be screened for tuberculosis and viral
hepatitis in accordance with published guidelines, and if positive,
treated according to standard medical practice prior to therapy with
ORENCIA.

Immunizations: Live vaccines should not be given concurrently
with ORENCIA or within 3 months of its discontinuation. The efficacy of
vaccination in patients receiving ORENCIA is not known. ORENCIA may
blunt the effectiveness of some immunizations. It is recommended that
JIA patients be brought up to date with all immunizations in agreement
with current immunization guidelines prior to initiating therapy with
ORENCIA.

Use in Patients with Chronic Obstructive Pulmonary Disease (COPD): Adult
COPD patients treated with ORENCIA developed adverse events more
frequently than those treated with placebo, including COPD
exacerbations, cough, rhonchi, and dyspnea. In adult RA studies, 97% of
COPD patients treated with ORENCIA developed adverse reactions versus
88% treated with placebo and respiratory disorders occurred more
frequently in patients treated with ORENCIA compared to those on placebo
(43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi,
and dyspnea. A greater percentage of adult RA patients treated with
ORENCIA developed a serious adverse event compared to those on placebo
(27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and
pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with RA
and COPD should be undertaken with caution, and such patients monitored
for worsening of their respiratory status.

Blood Glucose Testing: ORENCIA for intravenous administration
contains maltose, which may result in falsely elevated blood glucose
readings on the day of infusion when using blood glucose monitors with
test strips utilizing glucose dehydrogenase pyrroloquinoline quinone
(GDH-PQQ). Consider using monitors and advising patients to use monitors
that do not react with maltose, such as those based on glucose
dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase
or glucose hexokinase test methods. ORENCIA for subcutaneous (SC)
administration does not contain maltose; therefore, patients do not need
to alter their glucose monitoring.

Pregnancy: There are no adequate and well-controlled studies of
ORENCIA use in pregnant women and the data with ORENCIA use in pregnant
women are insufficient to inform on drug-associated risk. A pregnancy
registry has been established to monitor pregnancy outcomes in women
exposed to ORENCIA during pregnancy. Healthcare professionals are
encouraged to register patients by calling 1-877-311-8972.

Lactation: There is no information regarding the presence of
abatacept in human milk, the effects on the breastfed infant, or the
effects on milk production. However, abatacept was present in the milk
of lactating rats dosed with abatacept.

Most Serious Adverse Reactions: Serious infections (3% ORENCIA vs
1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo).

Malignancies: The overall frequency of malignancies was similar
between adult RA patients treated with ORENCIA or placebo. However, more
cases of lung cancer were observed in RA patients treated with ORENCIA
(0.2%) than those on placebo (0%). A higher rate of lymphoma was seen
compared to the general population; however, patients with RA,
particularly those with highly active disease, are at a higher risk for
the development of lymphoma. The potential role of ORENCIA in the
development of malignancies in humans is unknown.

Most Frequent Adverse Events (≥10%): Headache, upper respiratory
tract infection, nasopharyngitis, and nausea were the most commonly
reported adverse events in the adult RA clinical studies. Other events
reported in ≥5% of JIA patients were diarrhea, cough, pyrexia, and
abdominal pain. In general, the adverse events in JIA and adult PsA
patients were similar in frequency and type to those seen in adult RA
patients.

Note concerning ORENCIA administration options: Intravenous
dosing has not been studied in patients younger than 6 years of age. The
safety and efficacy of ORENCIA ClickJect™ Autoinjector for subcutaneous
injection has not been studied in patients under 18 years of age.

Please click here
to see the Full Prescribing Information.

About Bristol-Myers Squibb Immunoscience

With a robust pipeline of immunomodulatory therapies, Bristol-Myers
Squibb is committed to the discovery and development of transformational
medicines for patients suffering from immune-mediated disease. As we
learn more about the immune system in diseases with substantial unmet
medical needs, the potential for new therapies that modulate the immune
system continues to drive our research efforts.

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 about
Bristol-Myers Squibb, visit us at BMS.com or
follow us on LinkedInTwitterYouTube and Facebook.

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.
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, 2016 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.

References

    1.   ORENCIA® Prescribing Information. Bristol-Myers Squibb
Company, Princeton, NJ. June 2017.
2.

Psoriatic Arthritis. American College of Rheumatology. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Psoriatic-Arthritis.
Accessed May 8, 2017.

3.

Psoriatic Arthritis Overview. National Institutes of Health. https://www.niams.nih.gov/Health_info/Psoriatic_Arthritis/default.asp.
Accessed May 8, 2017.

4.

Mease P., Gottlieb A., Heijde H., et al. Efficacy and safety of
abatacept, a T-cell modulator, in a randomised, double-blind,
placebo-controlled, phase 3 study in psoriatic arthritis. Annals
of the Rheumatic Diseases.
2017

5.

About Psoriatic Arthritis. National Psoriasis Foundation. https://www.psoriasis.org/about-psoriatic-arthritis.
Accessed June 21, 2017.

6.

What is Psoriatic Arthritis? The Arthritis Foundation. http://www.arthritis.org/about-arthritis/types/psoriatic-arthritis/what-is-psoriatic-arthritis.php.
Accessed May 8, 2017.

7.

Gladman D, Antoni C, Mease P., et al. Psoriatic arthritis:
epidemiology, clinical features, course, and outcome. Annals of
the Rheumatic Diseases.
2005

8. Mease P, Genovese MC, Gladstein G. Abatacept in the treatment of
patients with psoriatic arthritis: Results of a six-month,
multicenter, randomized, double-blind, placebo-controlled, phase II
trial. Arthritis & Rheumatism. 2011;63(4):939-948.
 

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