Celgene Corporation
Nov 8, 2011
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Phase II Study Evaluating Apremilast as an Oral Treatment for Patients with Ankylosing Spondylitis Presented at ACR

Study Supports Clinical Potential of Apremilast; Underscores High Unmet Medical Need for Novel Oral Therapies

Based on Results, Celgene To Initiate Phase III Study to Further Evaluate Apremilast in Ankylosing Spondylitis

BOUDRY, Switzerland, Nov 08, 2011 (BUSINESS WIRE) --

Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG), today announced data from a Phase II study of apremilast, its investigational oral immunomodulatory compound, in patients with ankylosing spondylitis (AS) were presented at the American College of Rheumatology Scientific Meeting in Chicago, IL. Based on the data from this study, the company will be initiating a Phase III placebo-controlled trial with apremilast in ankylosing spondylitis during the first half of 2012.

The Spondylitis Trial of Apremilast for better Rheumatic Therapy (START) was a double-blind, placebo-controlled investigator-initiated pilot study conducted in subjects with AS. The primary objective of this study was to detect an efficacy signal using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

In the study, AS patients who had been symptomatic for at least two years, with their disease uncontrolled by conventional non-steroidal anti-inflammatory drugs and with daily spinal pain and stiffness for at least two weeks, were treated for 12 weeks with 30 mg BID apremilast or placebo. The treatment phase was followed by a 4-week observation phase.

Thirty-eight patients were randomized and 36 patients were evaluable for response. These patients were evaluated based on mean change from baseline across multiple parameters including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Functional Index (BASFI) and Metrology Index (BASMI). Additionally, plasma levels of sclerostin and serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) were measured at baseline and after 12 weeks.

At week 12, apremilast (n=17) was associated with a trend to greater mean improvement from baseline compared with placebo (n=19) in all parameters, including BASDAI, BASFI, BASMI and BASG. There was a significant mean percentage change from baseline in levels of sclerostin and RANKL compared to placebo, but not of OPG.

Clinical Parameter   Mean change from baseline (SD)   p value (ANCOVA)
  Apremilast (n=17)   Placebo (n=19)  
BASDAI   -1.59 (1.48)   -0.77 (1.47)   0.139
BASFI   -1.74 (1.91)   -0.28 (1.61)   0.108 (rank ANCOVA)
BASMI   -0.51 (1.02)   -0.21 (0.67)   0.617
Laboratory marker  

Mean percentage change from baseline
(SD) [No change=100%]

  p value
RANKL   73.2 (30.9)   108.2 (32.01)   0.04
OPG   97.8 (18.3)   92.8 (18.8)   0.4
RANKL:OPG Ratio   78.3 (33.8)   108.5 (34.6)   0.016
Sclerostin   84.8 (23.03)   110.1 (32.68)   0.015

More patients receiving apremilast versus placebo reported loose stools (26.3% vs. 10.5%) and headache (42.1% vs. 26.3%). There was no relevant difference in the incidence of diarrhea (10.5% in both arms), nausea (15.8% in both arms) or upper respiratory tract infections (31.6% in both arms) between the groups. There were no serious adverse events reported in the study.

These results are from an investigational study. Apremilast is not approved for the treatment of patients with ankylosing spondylitis or any other indication.

About Ankylosing Spondylitis

Ankylosing spondylitis is a form of arthritis that primarily affects the spine, although other joints can become involved. It causes inflammation of the spinal joints (vertebrae) that can lead to severe, chronic pain and discomfort. In the most advanced cases (but not in all cases), this inflammation can lead to new bone formation on the spine, causing the spine to fuse in a fixed, immobile position, sometimes creating a forward-stooped posture. This forward curvature of the spine is called kyphosis.

AS can also cause inflammation, pain and stiffness in other areas of the body such as the shoulders, hips, ribs, heels and small joints of the hands and feet. Sometimes the eyes can become involved (known as Iritis or Uveitis), and rarely, the lungs and heart can be affected.

The hallmark feature of ankylosing spondylitis is the involvement of the sacroiliac (SI) joints during the progression of the disease, which are the joints at the base of the spine, where the spine joins the pelvis.

In the United States alone, it is estimated that approximately 2.3 million people are affected by a spondyloarthropathy, the disease category of which AS is a part.

About Apremilast

Apremilast, an oral, targeted PDE4 inhibitor, is the lead investigational compound in the Celgene Inflammation and Immunology Franchise, and is in phase III clinical development for the treatment of moderate to severe psoriasis and psoriatic arthritis and in phase II trials in other debilitating inflammatory diseases, such as rheumatoid arthritis. The immune system is normally homeostatic, with mechanisms in place to turn off an immune response and avoid tissue damage that can result from chronic inflammation. Phosphodiesterase 4 (PDE4), an intracellular enzyme and the predominate PDE activity in immune cells, sustains inflammation by lowering the intracellular level of cAMP. Apremilast is an oral, targeted inhibitor of PDE4 and thus modulates expression of a network of pro- and anti-inflammatory mediators. Through targeted inhibition of PDE4, apremilast has the potential to treat a variety of autoimmune diseases including psoriasis, psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis.

About Celgene International Sàrl

Celgene International Sàrl, located in Boudry, in the Canton of Neuchâtel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at www.celgene.com.

This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.

SOURCE: Celgene International Sàrl

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