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11-Jun-2019

CELGENE’S LARGEST MULTINATIONAL REAL WORLD STUDY ILLUSTRATES OTEZLA’S EFFECTIVENESS ACROSS A VARIETY OF MANIFESTATIONS IN PATIENTS WITH MODERATE TO SEVERE PSORIASIS

OTEZLA® (apremilast) data showed notable clinical and quality of life improvements in patients with moderate to severe psoriasis affected by specific manifestations of the disease 

Patients with moderate skin involvement are a diverse group who may have significant disease activity and range of psoriasis manifestations, which may result in poor quality of life 

Celgene presented the first full data readout of its largest real world evidence study APPRECIATE involving 480 psoriasis patients from 6 European countries 

BOUDRY, Switzerland – 11 June 2019 – Celgene Corporation (NASDAQ:CELG), today announced full results from the APPRECIATE real-world evidence study. Data illustrated the effectiveness of OTEZLA® (apremilast) in delivering clinical and quality of life improvements in patients with moderate to severe psoriasis affected by specific manifestations of the disease, including pruritus and scalp, nail and palmoplantar involvement.[i] These results were presented at the 24th World Congress of Dermatology.

Within the pool of patients with moderate to severe psoriasis, the subset who have moderate psoriasis are a diverse group who may have significant disease activity and a range of specific psoriasis manifestations, which may result in poor quality of life (QoL) and comorbidities, adding to the burden and complexity of the disease. This results in the patient’s perception of their disease severity not always correlating with their clinically evaluated severity.[ii],[iii],[iv],[v]

APPRECIATE is a retrospective, cross-sectional study involving 480 patients from 87 sites in 6 countries in Europe. The study was designed to capture the clinical experience with OTEZLA as documented and described by clinicians and patients in a real world setting.1

Findings showed that despite having moderate skin involvemement as measured by a mean Psoriasis Area Severity Index (PASI) score of 12.5 (±8.4), a large proportion of patients (89.4%) suffered from specific manifestations of the disease at treatment initation, including pruritus (67.7%), and/or scalp (67.7%), nail (37.9%), and palmoplantar (23.8%) involvement.1

“Specific manifestations of psoriasis can have a large impact on quality of life. In patients with limited skin symptoms but who are affected by pruritus and/or scalp, nail and palmoplantar involvement, conventional systemic treatments may not be effective in aleviating their disease burden,” said Professor Matthias Augustin, Director Institute of Health Care Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf. “Given the difficulty in treating these areas, we’re pleased with the data from APPRECIATE which illustrates the effectiveness of OTEZLA in treating these manifestations.”

After 6(±1) months of OTEZLA treatment, physician’s ratings showed clinical improvement in pruritus, scalp, nail, and/or palmoplantar psoriasis for most patients continuing treatment (72.3%; n=347). There was also a notable improvement in skin-related outcomes in patients with available scores.1 Following 6±1 months of therapy, mean PASI score was 4.6 (n=241). In addition, patients with no specific manifestations beyond skin involvement noticed a PASI improvement from 10.9 to 4.7 after treatment and patients with one or more specific manifestations improved from 13.2 to 4.6.1

Most importantly, OTEZLA treatment improved the mean Dermatology Life Quality Index (DLQI) score, which assesses the health-related quality of life of adult patients suffering from a skin disease. Mean DLQI at treatment initiation was 13.4 (n=205) indicating a very large impact of disease on Quality of Life (QoL). Those continuing OTEZLA after 6±1 months of therapy and with available score had a mean DLQI score of 5.6 overall (n=141), which was largely comparable across specific manifestation subgroups.1

Reported adverse events were consistent with the known safety profile of OTEZLA.[vi] After 6± months of therapy, 72.3% of patients continued treatment with OTEZLA, of those that discontinued 11.7% were due to safety/tolerability reasons with the most common AEs being diarrhea (3.3%), nausea (3.3 %), and headache (1.9%).1

“In a complex, multifaceted disease such as psoriasis, real world data is increasingly important tofully understand the place and value of medicines. To this end, the APPRECIATE study, reflecting the use of OTEZLA across a variety of countries in clinical practice. provides particularly important insights, in patients with more moderate skin involment and with other specific disease manifestations,” said Volker Koscielny, Vice President Global Medical Affairs, Inflammation & Immunology at Celgene.

APPRECIATE adds to the body of evidence demonstrating that OTEZLA is an effective treatment option for patients with moderate to severe psoriasis, with notable improvements in QoL and disease severity for the overall population and in patients with specific manifestations of psoriasis.1

Celgene is committed to complementing the wealth of clinical data for OTEZLA with ongoing real-world evidence in psoriasis and psoriatic arthritis. Thousands of patients around the world are involved in Celgene-sponsored and investigator-initiated trials. Ongoing in Europe alone, there are 11 Celgene-sponsored observational prospective studies (six in psoriasis and five in psoriatic arthritis), two retrospective studies, and 11 patient registries (five in psoriasis and six in psoriatic arthritis) with OTEZLA.

About Psoriasis

Psoriasis affects 125 million people worldwide,[vii] including around 14 million people in Europe.5 It is a chronic and systemic inflammatory disorder, and is immune-mediated, meaning it is caused by an immune reaction in the body.5

Psoriasis lesions can often be found on areas close to the joints such as the elbows and knees but can also appear on the scalp.5,[viii] Nail psoriasis affects up to 50 percent of people with psoriasis.[ix] Up to 84 percent of people with psoriasis experience itching,[x] and over a third of patients actually cite itch as the most important factor contributing to their disease.[xi]

Around 75 percent of people living with psoriasis believe it has a negative impact on their QoL and 83 percent of patients with psoriasis actively conceal the visible signs of their disease.[xii],[xiii]

About OTEZLA

OTEZLA (apremilast) is an oral inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic AMP (cAMP). PDE4 inhibition results in increased intracellular cAMP levels, which is thought to indirectly modulate the production of inflammatory mediators.[xiv] OTEZLA was licensed by the European Commission in 2015 and is now approved in 30 countries globally, including 21 countries in Europe. Nearly 370,000 patients worldwide have been treated with OTEZLA since its approval.

About APPRECIATE

APPRECIATE is a multinational, retrospective, cross-sectional, observational study of adult psoriasis patients treated with OTEZLA, an oral phosphodiesterase 4 inhibitor, in real-world clinical practice. The study aims to assess patient characteristics, treatment outcomes, and benefits/limitations perceived by patients and physicians.

The study enrolled 480 patients from 87 sites across six countries - Austria, Germany, Ireland, Sweden, Switzerland, United Kingdom, and is still enrolling in Spain, making it Celgene’s largest real world evidence study in psoriasis Patients were a mean age 51.3 years and had a mean disease duration 18.6 years. Patients were contacted 6(±1) months after OTEZLA initiation and were treated according to routine clinical practice. Patient and physician questionnaires were completed 6(±1) months after treatment initiation during routine clinical visits. Analyses were performed using descriptive statistics in a pooled analysis of all patients and their physicians in the study centres.  

 

ADDITIONAL IMPORTANT SAFETY INFORMATION based on EU label

Therapeutic indications

OTEZLA (apremilast), alone or in combination with Disease Modifying Antirheumatic Drugs (DMARDs), is indicated for the treatment of active psoriatic arthritis in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy.

 

OTEZLA is indicated for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen and ultraviolet-A light (PUVA).

 

Contraindications
OTEZLA is contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients in the formulation.

 

OTEZLA is contraindicated during pregnancy.

 

Warnings and precautions
Patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

 

Diarrhoea, Nausea, and Vomiting

There have been post-marketing reports of severe diarrhoea, nausea, and vomiting associated with the use of OTEZLA. Most events occurred within the first few weeks of treatment. In some cases, patients were hospitalized. Patients 65 years of age or older may be at a higher risk of complications. If patients develop severe diarrhoea, nausea, or vomiting, discontinuation of treatment with apremilast may be necessary.

 

Psychiatric disorders

Apremilast is associated with an increased risk of psychiatric disorders such as insomnia and depression. Instances of suicidal ideation and behaviour, including suicide, have been observed in patients with or without history of depression (see section 4.8). The risks and benefits of starting or continuing treatment with apremilast should be carefully assessed if patients report previous or existing psychiatric symptoms or if concomitant treatment with other medicinal products likely to cause psychiatric events is intended. Patients and caregivers should be instructed to notify the prescriber of any changes in behaviour or mood and of any suicidal ideation. If patients suffered from new or worsening psychiatric symptoms, or suicidal ideation or suicidal attempt is identified, it is recommended to discontinue treatment with apremilast.

Severe renal impairment

Otezla should be dose reduced to 30 mg once daily in patients with severe renal impairment.

 

Underweight patients

Patients who are underweight at the start of treatment should have their body weight monitored regularly. In the event of unexplained and clinically significant weight loss, these patients should be evaluated by a medical practitioner and discontinuation of treatment should be considered.

 

Summary of the safety profile
The most commonly reported adverse reactions in Phase III clinical studies have been gastrointestinal (GI) disorders including diarrhoea (15.7%) and nausea (13.9%). These GI adverse reactions were mostly mild to moderate in severity, with 0.3% of diarrhoea and 0.3% of nausea reported as being severe. These adverse reactions generally occurred within the first 2 weeks of treatment and usually resolved within 4 weeks.

 

The other most commonly reported adverse reactions included upper respiratory tract infections (8.4%), headache (7.9%), and tension headache (7.2%). Overall, most adverse reactions were considered to be mild or moderate in severity. The most common adverse reactions leading to discontinuation during the first 16 weeks of treatment were diarrhoea (1.7%), and nausea (1.5%). The overall incidence of serious adverse reactions was low and did not indicate any specific system organ involvement.

 

Hypersensitivity reactions were uncommonly observed in apremilast clinical studies.

 

Special populations 

Elderly patients

No dose adjustment is required for this patient population.

 

Patients with renal impairment

No dose adjustment is needed in patients with mild and moderate renal impairment. The dose of apremilast should be reduced to 30 mg once daily in patients with severe renal impairment (creatinine clearance of less than 30 mL per minute estimated by the Cockcroft-Gault equation). For initial dose titration in this group, it is recommended that apremilast be titrated using only the AM schedule listed in Table 1 of the SmPC and the PM doses be skipped.

 

Patients with hepatic impairment

No dose adjustment is necessary for patients with hepatic impairment.

 

Paediatric population

The safety and efficacy of apremilast in children aged 0 to 17 years have not been established. No data are available.

 

Please click here for Full Prescribing Information (EU Label)  

 

About Celgene

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. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.

 

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. Celgene undertakes 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, including factors related to the proposed transaction between Bristol-Myers Squibb and Celgene, such as, but not limited to, the risks that: management’s time and attention is diverted on transaction related issues; disruption from the transaction makes it more difficult to maintain business, contractual and operational relationships; pending legal proceedings or any future litigation instituted against Bristol-Myers Squibb, Celgene or the combined company could delay or prevent the proposed transaction; and Bristol-Myers Squibb, Celgene or the combined company is unable to retain key personnel


[i] M Augustin, et al. Characteristics and Outcomes of Patients Treated With Apremilast in the Real World: Results From the APPRECIATE Study. Presented at the World Congress of Dermatology. 10-15 June. Milan, Italy.

[ii] Mrowietz U, et al. Arch Dermatol Res. 2011;303:1–10.

[iii] Merola JF, et al. Dermatol Ther. 2018;e12589.

[iv] Feldman SR, et al. Am Health Drug Benefits. 2016;9:504–13.

[v] Augustin M, et al. J Eur Acad Dermatol Venereol. 2012;26:1–16.

[vi] Crowley J, Thaçi D, Joly P, et al. J Am Acad Dermatol. 2017;77(2):310-317.

[vii] International Federation of Psoriasis Associations. Our Cause: Psoriasis. Available at: https://ifpa-pso.com/our-cause/ Last Accessed: July 2019.

[viii] Van de Kerkhof, et al. Dermatology. 1998;197:326-34.

[ix] Tan EST, et al. Nail psoriasis: a review, Am J Clin Dermatol; 2012;13:375–388.

[x] Yosipovitch et al, 2000. The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis. British Journal of Dermatology. 2000;143:969.

[xi] Lebwohl MG et al, 2014. Patient perspectives in the management of psoriasis: Results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. Journal of the

American Academy of Dermatology. 2014;70(5):871-81.e1-30.

[xii] Bhosle M, et al. Health Qual Life Outcomes. 2006;4(35).

[xiii] Armstrong, et al. PLOS One. 2012;12:e52935.

[xiv] PH Schafer et al. Br J Pharmacol. 2010;159:842–855.

 This medicine is subject to additional safety monitoring. This will allow quick identification of new safety
information. Healthcare professionals are asked to report any suspected adverse reactions. Adverse events in any 
patient or subject receiving a Celgene product should be reported to Celgene Drug Safety: Tel: 0808 2389908; 
email: drugsafetyuk@celgene.com. Healthcare professionals are also asked to report suspected adverse reactions 
via the Yellow Card Scheme at https://yellowcard.mhra.gov.uk (Freephone 0800 731 6789). 

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Last Updated: 11-Jun-2019