Data on Two Novel Investigational Bristol-Myers Squibb Compounds in Clinical Development for Patients with Rheumatoid Arth

  • Five presentations to feature clinical and pre-clinical data
  • Results from Phase II clinical trials support continued development

NEW YORK--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE:BMY) today announced that results from clinical and pre-clinical studies involving two of its immunology pipeline compounds, BMS-945429 (ALD518) and BMS-582949, will be shared during five presentations at the American College of Rheumatology (ACR) Annual Scientific Meeting being held in Atlanta from November 6 to 11. The five presentations related to these early-stage compounds are in addition to 12 ORENCIA® (abatacept) abstracts covering the intravenous (I.V.) and subcutaneous formulations, which will also be presented at ACR. The presentation of these data highlights the company’s continued commitment to exploring new treatment options addressing unmet medical need for patients living with rheumatoid arthritis (RA), via different mechanisms and I.V., subcutaneous and oral routes of administration.

BMS-945429 (ALD518) is a monoclonal antibody directed against interleukin-6, a cytokine protein known to play a key role in the inflammatory cascade in RA.1 Bristol-Myers Squibb is developing this compound under a licensing agreement with Alder Biopharmaceuticals. BMS-582949 is an oral dual-action p38 kinase inhibitor, which inhibits the activation and functional activity of a protein involved in regulating inflammatory processes important in RA.2 Bristol-Myers Squibb plans to initiate new clinical trials for these Phase II compounds next year.

The five presentations featuring BMS-945429 (ALD518) and BMS-582949 at ACR are as follows:

             
Date and Time     Presentation Title and Number     Lead Author

Poster Presentation
November 9
9:00 a.m. – 11:00 a.m.
Halls B1 & B2

   

ALD518 (BMS-945429), a High-Affinity
Anti-Interleukin-6 Monoclonal Antibody,
Provides Improvements in Health-Related
Quality of Life (HRQoL) in Patients with
Rheumatoid Arthritis (RA) and an Inadequate
Response to Methotrexate (1096)

   

V. Strand, Stanford
University, Palo Alto,
CA

Poster Presentation
November 9

9:00 a.m. – 11:00 a.m.
Halls B1 & B2

   

Proof of Concept Study for a Potent p38
MAPK Dual-Action Inhibitor BMS-582949
in Subjects with RA Receiving Concomitant
Methotrexate (1119)

   

M. Genovese,
Stanford University,
Palo Alto, CA

Poster Presentation
November 9

9:00 a.m. – 11:00 a.m.
Halls B1 & B2

   

Safety, Pharmacokinetics and
Pharmacodynamics of ALD518 (BMS-
945429), a High-Affinity Monoclonal
Antibody Directed Against Interleukin-6 (IL-
6) Administered by Subcutaneous Injection:
A Phase I Trial (1124)

   

S. Shakib, Royal
Adelaide Hospital,
Adelaide, Australia

Poster Presentation
November 10

9:00 a.m. – 11:00 a.m.
Halls B1 & B2

   

BMS-582949 is a Dual-Action p38 Kinase
Inhibitor Well Suited to Avoid Resistance
Mechanisms That Increase p38 Activation in
Cells (1513)

   

G. Schieven, Bristol-
Myers Squibb

Oral Presentation
November 10
4:30 p.m. – 4:45 p.m.
B405, 406, 407

   

ALD518 (BMS-945429), a High-Affinity
Monoclonal Antibody Directed Against
Interleukin-6, Reduces Disease Activity and
Achieves Remission in Patients with
Rheumatoid Arthritis and Inadequate
Response to Methotrexate (2168)

   

P. Mease, University
of Washington,
Seattle, WA

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic,3 chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, swelling and fatigue.4 RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment.5

RA affects about 1% of the world's population,6 including more than one million people in the United States.3 The condition is more common in women than in men, who account for 75% of patients diagnosed with RA.4

About ORENCIA® (abatacept)

ORENCIA is a prescription medicine that is used to treat adults with moderate to severe RA including those who have not been helped enough by other medicines for RA. ORENCIA may prevent further damage to bones and joints, and may help the individual’s ability to perform daily activities. In adults, ORENCIA may be used alone or with disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.

ORENCIA also reduces signs and symptoms in children and adolescents six years of age and older with moderate to severe polyarticular juvenile idiopathic arthritis (JIA). In children and adolescents, ORENCIA may be used alone or with methotrexate (MTX).

ORENCIA should not be used with TNF antagonists and is not recommended for use with other biologic RA therapy, such as anakinra.

Important Safety Information About ORENCIA® (abatacept)

Concomitant Use with TNF antagonists: Concurrent therapy with ORENCIA and a biologic DMARD is not recommended. In controlled clinical trials, adult patients receiving concomitant 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: Less than 1% of adult patients treated with ORENCIA experienced hypersensitivity reactions, including some cases of anaphylaxis or anaphylactoid reactions. Other events potentially associated with drug hypersensitivity, such as hypotension, urticaria and dyspnea, each occurred in less than 0.9% of patients treated with ORENCIA and generally occurred within 24 hours of infusion. There was one case of a hypersensitivity reaction with ORENCIA in JIA clinical trials (0.5%; n = 190). Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use in the event of a reaction.

Infections: Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA® (abatacept) 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 as it 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® (abatacept) developed adverse events more frequently than those treated with placebo (97% vs. 88%, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs. 24%, respectively), including COPD exacerbations, cough, rhonchi and dyspnea. A greater percentage of 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 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 pyrroloquinolinequinone (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.

Pregnant and Nursing Mothers: ORENCIA should be used during pregnancy only if clearly needed. The risk for development of autoimmune diseases in humans exposed in utero to abatacept has not been determined. Nursing mothers should be informed of the risk/benefit of continued breast-feeding or discontinuation of the drug. A pregnancy registry has been established to monitor fetal outcomes. Healthcare professionals are encouraged to register pregnant patients exposed to ORENCIA by calling 1-877-311-8972.

Most Serious Adverse Reactions: Serious infections (3.0% ORENCIA vs. 1.9% placebo) and malignancies (1.3% ORENCIA vs. 1.1% placebo). In general, adverse events in pediatric and adolescent patients were similar in frequency and type to those seen in adult patients.

Malignancies: The overall frequency of malignancies was similar between adult patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in 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.

For Full US Prescribing Information, visit www.ORENCIA.com or www.bms.com.

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 www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

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. Among other risks, there can be no guarantee that either of the compounds described in this release will move from exploratory development into full product development, that clinical trials of these compound will support regulatory filings, or that either of these compounds will receive regulatory approval or become a commercially successful product. Forward-looking statements in the 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, 2009, its Quarterly Reports on Form 10-Q, and 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  

Nishimoto N, Ito A, Ono M, Tagoh H, Matsumoto T, Tomita T, Ochi T, Yoshizaki K; IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor. Int Immunol. 2000;12(2):187-193.

2

Saklatvala J; The p38 MAP kinase pathway as a therapeutic target in inflammatory disease. Curr Opin Pharmacol. 2004; Aug, 4(4):372-377.

3

Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;Jan;58(1):15-25.

4 American College of Rheumatology, Practice Management, Rheumatoid Arthritis. Available at: http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ra.asp. Accessed September 2010.
5

National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health. U.S. Department of Health and Human Services. Rheumatoid Arthritis. May 2004.

6

Lee DM, Weinblatt ME. Rheumatoid Arthritis. The Lancet. 2001;358:903-11.



CONTACT:

Bristol-Myers Squibb Company
Media:
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[email protected]
or
Investors:
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INDUSTRY KEYWORDS:   Health  Biotechnology  Clinical Trials  Pharmaceutical

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