Celgene Corporation
Oct 7, 2014
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Celgene to Present Long-Term Efficacy and Safety Data on Oral OTEZLA® (apremilast) in Plaque Psoriasis And Psoriatic Arthritis at European Academy of Dermatology and Venereology Congress

New analyses of ESTEEM trials evaluate safety, efficacy and tolerability of OTEZLA in patients with moderate to severe plaque psoriasis

Analysis of PALACE 52-week data assesses impact of OTEZLA on signs and symptoms of psoriatic arthritis

11 featured abstracts underscore growing body of evidence and depth of the OTEZLA clinical development program in plaque psoriasis and psoriatic arthritis

OTEZLA recently approved by the U.S Food and Drug Administration for moderate to severe plaque psoriasis patients who are candidates for phototherapy or systemic therapy

BOUDRY, Switzerland - (7 October, 2014) - Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG), today announced that the latest research findings on OTEZLA® (apremilast), the Company's oral, selective inhibitor of phosphodiesterase 4 (PDE4), in plaque psoriasis and psoriatic arthritis will be presented at the 23rd European Academy of Dermatology and Venereology (EADV) Congress in Amsterdam, October 8 - 12, 2014. In total, 11 abstracts (two oral presentations and nine e-Posters) will be presented at the meeting.
 
OTEZLA data to be presented include long-term (52-week) results from Celgene's pivotal trial, ESTEEM 2 and pooled analyses of safety and tolerability results from the ESTEEM 1 and 2 studies in patients with moderate to severe plaque psoriasis. Additional analyses will evaluate the effect of OTEZLA on pruritus (itching), difficult-to-treat areas such as nail and scalp, and palmoplantar (hand and feet) psoriasis, work productivity and improvements in health-related quality of life.

An analysis of long-term results from the PALACE clinical trial program evaluating OTEZLA in patients with active psoriatic arthritis will also be presented at the meeting. The analysis assesses the effect of OTEZLA treatment through 52 weeks on the signs and symptoms of psoriatic arthritis, including enthesitis (inflammation at sites where tendons or ligaments insert into bone) and dactylitis (inflammation of an entire finger or toe) in patients with pre-existing enthesitis or dactylitis.

During the Congress, Celgene will host a variety of programs focusing on the unmet needs for people living with psoriasis and psoriatic arthritis, including a symposium for healthcare professionals and programs for patient/professional advocacy organizations and media.

"The presentation of OTEZLA data at the upcoming EADV annual meeting not only reinforces OTEZLA's impact in psoriasis, but also shows the depth of the clinical development programs in plaque psoriasis and psoriatic arthritis," said Scott Smith, President Inflammation & Immunology for Celgene Corporation. "EADV is an important congress for the dermatology community and Celgene's presence at this year's congress underscores our commitment to the development of new treatment options for people living with inflammatory diseases."

The following abstracts on OTEZLA will be presented in oral and/or e-Poster sessions as an exchange of scientific and clinical information by clinical investigators (all times, CEST):

Abstracts at a Glance
Oral Presentation FC05.9; Friday, October 10, 3:57 - 4:06 PM
Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Moderate to Severe Psoriasis: Results of a Phase 3, Randomized, Controlled Trial (ESTEEM 2); Carle Paul, MD
Location: G106

Oral Presentation FC05.2; Friday, October 10, 2:54 - 3:03 PM
Long-term Safety and Tolerability of Apremilast in Patients with Psoriasis: Pooled Safety Analysis of Two Phase 3, Randomized, Controlled Trials (ESTEEM 1 and 2); Kristian Reich, MD
Location: G106

Poster Number P1691
Effect of Apremilast on Patient Reported Outcomes in Patients with Moderate to Severe Plaque Psoriasis in the ESTEEM 1 trial; April Armstrong, MD
Location: e-Poster area

Poster Number P1690
Change in Weight with Apremilast, an Oral Phosphodiesterase 4 Inhibitor: Pooled Analysis of the ESTEEM 1 and ESTEEM 2 Trials; Kristian Reich, MD
Location: e-Poster area

Poster Number P1689
Psychiatric Disorders and Depression Incidence with Apremilast, an Oral Phosphodiesterase 4 Inhibitor: Pooled Analysis of the ESTEEM 1 and ESTEEM 2 Trials; Alan Menter, MD
Location: e-Poster area

Poster Number P1688
Effects of Apremilast on Health-Related Quality of Life in Patients with Moderate to Severe Plaque Psoriasis: 16-Week Results From the ESTEEM 2 Trial; Melinda Gooderham, MD
Location: e-Poster area

Poster Number P1687
Apremilast in Moderate to Severe Plaque Psoriasis: 32-Week Results in Patients with Nail, Scalp, and Palmoplantar Involvement (ESTEEM 2); Jeffrey Crowley, MD
Location: e-Poster area

Poster Number P1682
Effects of Apremilast on Pruritus in Patients with Moderate to Severe Plaque Psoriasis: Results from the ESTEEM 1 and 2 Trials; Gil Yosipovitch, MD
Location: e-Poster area

Poster Number P1679
Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results of Phase 3, Randomized, Placebo-Controlled Trials (PALACE 1, 2, and 3); Sergio Chimenti, MD
Location: e-Poster area

Poster Number P1683
The Impact of Apremilast Therapy on Work Productivity Among Patients with Moderate to Severe Plaque Psoriasis: Pooled Analysis of 2 Phase 3 Studies; Ulrich Mrowietz, MD
Location: e-Poster area

Poster Number TBA
The Impact of Apremilast Therapy on Work Productivity Among Patients with Moderate to Severe Plaque Psoriasis: Pooled Analysis of 2 Phase 3 Studies; Tom Tencer, MD
Location: e-Poster area

The views expressed and the techniques presented by the speakers at the 23rd EADV Congress in Amsterdam, The Netherlands are not necessarily shared or endorsed by the European Academy of Dermatology and Venereology.

About ESTEEM 1 and 2
ESTEEM 1 and 2 are two large pivotal phase III randomized, placebo-controlled studies evaluating OTEZLA in patients with a diagnosis of moderate to severe plaque psoriasis for at least 12 months prior to screening, and who were also candidates for phototherapy or systemic therapy. Approximately 1,257 patients were randomized 2:1 to receive either OTEZLA 30 mg twice daily or placebo after an initial five-day titration period, for the first 16 weeks, followed by a maintenance phase from weeks 16-32 in which placebo patients were switched to OTEZLA 30 mg twice daily through week 32, and a randomized withdrawal phase for responders from week 32 to week 52 based on their initial OTEZLA randomization and Psoriasis Area and Severity Index (PASI)-75 response. Approximately 30 percent of all patients had received prior phototherapy and 54 percent had received prior conventional systemic and/or biologic therapy. Approximately one-third of patients had not received prior phototherapy, conventional systemic nor biologic therapy.  A total of 18 percent of patients had a history of psoriatic arthritis.

The primary endpoint of the ESTEEM 1 and ESTEEM 2 studies was the proportion of patients who achieved PASI-75 at week 16. The major secondary endpoint was the proportion of patients who achieved a static Physician Global Assessment score of clear (0) or almost clear (1) at Week 16.

About PALACE Program
PALACE 1, 2 and 3 are the pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. Across these studies, approximately 1,500 patients were randomized 1:1:1 to receive either OTEZLA 20 mg twice daily, OTEZLA 30 mg twice daily or identically-appearing placebo, for 16 weeks. At week 16, some placebo-treated patients were randomized to one of the two OTEZLA groups, while others remained on placebo through week 24. After week 24, patients began a subsequent long term, open-label, active treatment phase. The PALACE 1, 2 and 3 studies included a wide spectrum of patients with active psoriatic arthritis, including those who had been previously treated with oral disease-modifying antirheumatic drugs (DMARDs), and/or biologics, with some patients who had previously failed a tumor necrosis factor (TNF) blocker.

The primary endpoint of the PALACE 1, 2, and 3 studies was the modified American College of Rheumatology criteria for 20 percent improvement (ACR20) at week 16. Secondary endpoints included other measures of signs and symptoms of psoriatic arthritis, physical functioning and patient-reported outcomes.

Taken together, the PALACE program is the largest psoriatic arthritis program to date intended for regulatory submission.

About OTEZLA
OTEZLA is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which OTEZLA exerts its therapeutic action in patients with psoriasis or psoriatic arthritis is not well defined.

OTEZLA was approved on March 21, 2014 by the U.S. Food and Drug Administration (FDA) for the treatment of adults with active psoriatic arthritis and on September 23, 2014 for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. A combined psoriatic arthritis/plaque psoriasis Marketing Authorization Application (MAA) in Europe was submitted to health authorities in the fourth quarter of 2013.

INDICATIONS AND IMPORTANT SAFETY INFORMATION

Indications
Otezla® (apremilast) is indicated for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

OTEZLA is indicated for the treatment of adult patients with active psoriatic arthritis.

Important Safety Information
Depression: Carefully weigh the risks and benefits of treatment with Otezla for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on Otezla. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur.

Psoriasis: Treatment with Otezla is associated with an increase in adverse reactions of depression. During clinical trials, 1.3% (12/920) of patients treated with Otezla reported depression compared to 0.4% (2/506) on placebo; 0.1% (1/1308) of Otezla patients discontinued treatment due to depression compared with none on placebo (0/506). Depression was reported as serious in 0.1% (1/1308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezla attempted suicide; one patient on placebo committed suicide.

Psoriatic Arthritis: During clinical trials, 1.0% (10/998) of patients treated with Otezla reported depression or depressed mood compared to 0.8% (4/495) treated with placebo; 0.3% (4/1441) of patients treated with Otezla discontinued treatment due to depression or depressed mood compared with none in placebo treated patients (0/495). Depression was reported as serious in 0.2% (3/1441) of patients exposed to Otezla, compared to none in placebo treated patients (0/495). Suicidal ideation and behavior were observed in 0.2% (3/1441) of patients on Otezla, compared to none on placebo (0/495). Two patients who received placebo committed suicide compared to none on Otezla.

Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla.

Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients treated with Otezla and in 5% (19/382) of patients treated with placebo. Body weight loss of ≥10% occurred in 2% (16/784) of patients treated with Otezla compared to 1% (3/382) of patients treated with placebo.

Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% of patients taking Otezla and in 3.3% of patients taking placebo. Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla.
Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP450 enzyme inducers (eg, rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended.

Adverse Reactions
Psoriasis: Adverse reactions reported in ≥5% of patients were (Otezla%, placebo %): diarrhea (17, 6), nausea (17, 7), upper respiratory tract infection (9, 6), tension headache (8, 4), and headache (6, 4).

Psoriatic Arthritis: Adverse reactions reported in ≥2% of patients taking Otezla, that occurred at a frequency at least 1% higher than that observed in patients taking placebo, for up to 16 weeks (after the initial 5-day titration), were (Otezla%, placebo%): diarrhea (7.7, 1.6); nausea (8.9, 3.1); headache (5.9, 2.2); upper respiratory tract infection (3.9, 1.8); vomiting (3.2, 0.4); nasopharyngitis (2.6, 1.6); upper abdominal pain (2.0, 0.2).

Use in Specific Populations
Pregnancy and Nursing Mothers: Otezla is Pregnancy Category C; it has not been studied in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether apremilast or its metabolites are present in human milk. Caution should be exercised when Otezla is administered to a nursing woman.

Renal Impairment: Otezla dosage should be reduced in patients with severe renal impairment (creatinine clearance less than 30 mL/min); for details, see Dosage and Administration, Section 2, in the Full Prescribing Information.
  
Please click here for Full Prescribing Information.

About Psoriasis
Psoriasis is an immune-mediated, non-contagious chronic inflammatory skin disorder of unknown cause. The disorder is a chronic recurring condition which varies in severity from minor localized patches to complete body coverage. Plaque psoriasis is the most common type of psoriasis. About 80 percent of people who develop psoriasis have plaque psoriasis, which appears as patches of raised, reddish skin covered by silvery-white scales. These patches, or plaques, frequently form on the elbows, knees, lower back, and scalp. Psoriasis occurs nearly equally in males and females. An estimated 125 million people worldwide have psoriasis. To learn more about the role of PDE4 in inflammatory diseases, go to www.discoverpde4.com.

About Psoriatic Arthritis
Psoriatic arthritis is a painful, chronic inflammatory disease characterized by pain, stiffness, swelling and tenderness of the joints, inflammation of specific ligaments and tendons, and decrease in physical functioning. It is estimated that nearly 38 million people worldwide have psoriatic arthritis. Psoriatic arthritis can impact day-to-day activities and has been reported to increase work disability. Common signs and symptoms of psoriatic arthritis include pain, stiffness, and swelling in joints. To learn more about psoriatic arthritis, go to www.discoverpsa.com. To learn more about the role of PDE4 in inflammatory diseases, go to www.discoverpde4.com.

About Celgene
Celgene International Sàrl, located in Boudry, 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 www.celgene.com.

Forward-Looking Statements
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 other reports filed with the Securities and Exchange Commission.

For inquiries, please contact:

Investors:
Patrick E. Flanigan III
Vice President, Investor Relations
908-673-9969

Media:
Catherine Cantone
Director, Corporate Communications
732-564-3592