Market Overview

Bristol-Myers Squibb's ORENCIA® (abatacept) Receives Second European Commission Approval in Less than a Year – New Approval for Treatment of Active Psoriatic Arthritis (PsA)1


Patients demonstrated improved disease response in two clinical
trials that included both TNF-naïve and challenging to treat TNF-exposed
patients with active musculoskeletal involvement

Squibb Company
(NYSE:BMY) announced today that the European
Commission (EC) has approved ORENCIA alone or in combination with
methotrexate for the treatment of active Psoriatic Arthritis (PsA) in
adult patients for whom the response to previous disease-modifying
antirheumatic drug (DMARD) therapy, including methotrexate, has been
inadequate, and additional systemic therapy for psoriatic skin lesions
is not required.1

This approval, which allows for the expanded marketing of ORENCIA as a
treatment for PsA in all 28 Member States of the EU, marks the second
new indication for ORENCIA in less than a year; in September 2016, the
European Commission approved ORENCIA, in combination with methotrexate
(MTX), for the treatment of highly active and progressive disease in
adult patients with rheumatoid arthritis (RA) not previously treated
with MTX. PsA becomes the third autoimmune condition, along with
rheumatoid arthritis and juvenile idiopathic arthritis, for which
ORENCIA is approved to treat in Europe.1

"This EC approval builds on the well-established profile of ORENCIA in
Rheumatoid Arthritis and exemplifies our commitment to ongoing clinical
research of ORENCIA as a potential treatment for autoimmune conditions
where treatment options are limited or where patients have not been
helped enough by other medications," said Brian J. Gavin, Ph.D., Vice
President, ORENCIA Development Lead at Bristol-Myers Squibb. "Despite
the current availability of medications, there are many people with
active Psoriatic Arthritis who are in need of a new treatment option;
the approval of ORENCIA now provides a novel immunotherapy approach that
may help these patients."

The approval was based on results from two randomized, double-blind,
placebo-controlled studies (Studies PSA-I and PSA-II) in which a higher
proportion of patients achieved an ACR 20 response, the primary
endpoint, after treatment with ORENCIA 10 mg/kg intravenous (IV) or 125
mg subcutaneous injection (SC) compared to placebo at Week 24: 47.5%
versus 19.0% and 39.4% versus 22.3% (p< 0.05), respectively.1
Responses were seen regardless of prior tumor necrosis factor inhibitor
(TNFi) treatment in both studies.1

In the phase 3 study, PsA-II, the proportion of radiographic
non-progressors (≤0 change from baseline) in total PsA-modified SHS on
x-rays at Week 24 was greater with ORENCIA 125 mg SC (42.7%) than
placebo (32.7% (10.0 [1.0, 19.1] estimate of difference [95% CI]).1
There were no adverse reactions that occurred at ≥ 2% in either
treatment group during the 24-week placebo-controlled period. The
overall safety profile was comparable between studies PsA-I and PsA-II
and consistent with the safety profile in rheumatoid arthritis.1
Headache, upper respiratory tract infection, nasopharyngitis, and nausea
were the most commonly reported adverse events occurring at a rate of ≥
10% in patients taking ORENCIA in the adult RA clinical studies.1

In PsA, the immune system attacks healthy joints and skin.3 T-cell
activation is involved in the pathogenesis of PsA.4 The
costimulation blockade of ORENCIA inhibits T-cell activation and the
resulting cascade of events that contribute to joint destruction. Both
IV and SC injection formulations of ORENCIA are now approved to treat
adult patients with active PsA.

Additional Information About Studies PSA-I and

The efficacy of ORENCIA was assessed in two
randomized, double-blind, placebo-controlled studies (Studies PsA-I and
PsA-II) in 594 adult patients,1 with a disease duration more
than 7 years.4,5 Patients had active PsA (≥ 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.1
In PsA-I and PsA-II, 37% and 61% of patients, respectively, were treated
with 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, 170 patients received placebo or ORENCIA 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 10 mg/kg IV every 28 days.1
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,
followed by open label ORENCIA 10 mg/kg monthly IV every month.1
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, also known as ASTRAEA, 424 patients were randomized 1:1 to
receive weekly doses of SC placebo or ORENCIA 125 mg without a loading
dose for 24 weeks, followed by open-label ORENCIA 125 mg SC weekly.1
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

About Psoriatic Arthritis
arthritis (PsA) is a chronic6, inflammatory disease that can
affect both the skin and musculoskeletal system.2 PsA can
cause joint pain, stiffness and reduced range of motion, and can
eventually lead to irreparable joint damage.2 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.2 Men and women are equally at risk.2
Early recognition, diagnosis and treatment of Psoriatic Arthritis are
critical to relieve pain and inflammation and help prevent joint damage.2

U.S. Indications/Usage and Important Safety Information for ORENCIA®

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

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

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

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

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
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
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 or
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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.

1. ORENCIA® Annex I:
Summary of Product Characteristics. Bristol-Myers Squibb Company,
Princeton, NJ. June 2017.
2. Psoriatic Arthritis Overview. National
Institutes of Health.
Accessed May 8, 2017.
3. What is Psoriatic Arthritis? The Arthritis
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.
5. 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.
6. Psoriatic Arthritis. American
College of Rheumatology.
Accessed May 8, 2017.

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