New Data Reinforce Safety Profile Of ENBREL(REG) (Etanercept)

Main Category: Eczema / Psoriasis
Also Included In: Biology / Biochemistry;  Clinical Trials / Drug Trials
Article Date: 07 Oct 2006 - 7:00 PDT


There was good news for psoriasis patients this week, as the latest study confirming the established safety profile of ENBREL® (etanercept) for up to 2.5 years,was presented at the 15th European Academy of Dermatology and Venereology (EADV) Congress. ENBREL is a biologic, meaning a biotechnologically produced medicine, which acts on one of the root causes of psoriasis by targeting one of the key mediators of the inflammatory process. It is the number one biologic prescribed worldwide and is now approved in 25 mg and 50 mg prefilled syringes offering flexibility to tailor treatment according to patient needs.

According to Bruce Strober MD PhD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University, "These results are important because they confirm the safety profile of ENBREL, which is key information in the context of wider discussion about the long-term use of biologics."

The 48-week open label (OL) extension study (n=921) enrolled patients from two blinded, randomized, placebo-controlled "parent" studies (PS). The OL study confirmed that the overall safety profile of ENBREL did not change with extended dosing for up to 2.5 years.(1,2) No cases of demyelinating diseases, tuberculosis, opportunistic infections or lymphoma were reported in the study.(1,2) These findings reinforce the conclusions of an earlier 96-week study of ENBREL 50 mg twice weekly in which the rate of adverse events was similar to that of placebo, and no new safety signals were identified.

In one of the parent studies, at 24 weeks patients were discontinued from treatment and treatment was re-initiated when at least half of the improvement achieved through week 24 was lost. With re-treatment, PASI 75 rates were similar to those attained during the initial treatment course, resulting in repeated success after re-treatment., There was no treatment interruption in the other parent study.

In Europe, the recommended dose of ENBREL for plaque psoriasis is 25 mg administered twice weekly. Alternatively, 50 mg given twice weekly may be used for up to 12 weeks followed, if necessary, by a dose of 25 mg twice weekly. Treatment with ENBREL should continue until remission is achieved, for up to 24 weeks. Treatment should be discontinued in patients who show no response after 12 weeks. If re-treatment with ENBREL is indicated, the dose should be 25 mg twice weekly for up to 24 weeks.

"These data reveal an important, practical characteristic of ENBREL in showing that patients on interrupted treatment, after reinitiating therapy, regained similar positive efficacy results as the patients with uninterrupted treatment", said Dr Wolfram Sterry, professor and chairman, department of dermatology, University Hospital Charite, Humboldt University, Germany. "In real life, treatment of psoriasis patients is often suspended for a variety of reasons and then restarted."

The new ENBREL prefilled syringes offer patients an easy to use treatment option because it does not require reconstitution as all doses are premixed and prefilled.(5) ENBREL is the only biologic with two ready to use dosing options.(5) The prefilled formulation is bioequivalent to ENBREL powder-for-mixing.

In the European Union, ENBREL is approved for the treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA (Psoralen [a light-sensitizing medication] combined with exposure to ultraviolet light A [UVA]).(3) ENBREL is also approved for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate.(3)

Also in the European Union, ENBREL in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including methotrextate (unless contraindicated), has been inadequate. ENBREL can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. ENBREL is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. ENBREL, alone or in combination with methotrexate, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.(3) ENBREL is also approved for the treatment of active polyarticular juvenile idiopathic arthritis in children and adolescents aged 4 to 17 years who have had an inadequate response to, or who have proved intolerant of, methotrexate.(3) ENBREL has not been studied in children aged less than 4 years. ENBREL is also approved for the treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.(3)

European physicians have become familiar with the benefits and long-term tolerability profile of ENBREL since it was approved six years ago. Worldwide, 441,000 patients have been treated with ENBREL. It acts by binding tumor necrosis factor (TNF),(3) one of the dominant inflammatory cytokines or regulatory proteins that plays an important role in both normal immune function and the cascade of reactions that causes the inflammatory processes of psoriasis, psoriatic arthritis and RA.(3) The binding of ENBREL to TNF inhibits the activity of the bound TNF.(3)

Since the product was first introduced, serious infections, some involving death, have been reported in patients using ENBREL.(3) Patients should tell their doctors if they currently have an infection or are prone to getting infections. Patients should not start ENBREL if they have an infection(3) of any type or an allergy to ENBREL or its components. ENBREL should be used with caution in patients prone to infection.(3)

There have been reports of serious nervous-system disorders such as multiple sclerosis and/or inflammation of the nerves of the eyes.(3) Patients should inform their doctor if they have ever had any of these disorders or if they develop them after starting ENBREL. Patients should also tell their doctor if they have ever been treated for heart failure.(3) There also have been rare reports of serious blood disorders, some involving death.(3)

Patients should contact their doctor immediately if they develop symptoms such as persistent fever, bruising, bleeding, or paleness.(3) If a patient's doctor confirms serious blood problems, patients may need to stop using ENBREL.(3)

The most common adverse events observed during the double blind, placebo-controlled portions of three clinical trials in patients with psoriasis were infections and injection-site reactions.(3) Among patients with plaque psoriasis treated in placebo-controlled trials, the frequency of serious adverse events was about 1% of 933 patients treated with Enbrel compared with 1% of 414 placebo-treated patients.(3)

Twenty-three (23) malignancies were reported in patients with plaque psoriasis treated with ENBREL in double blind and open- label studies of up to 15 months involving 1,261 patients treated with ENBREL.(3)

Psoriasis affects 5.1 million people in Europe. The most common form of psoriasis is plaque psoriasis (psoriasis vulgaris), which occurs in approximately 80% of all patients with psoriasis. In plaque psoriasis, it is likely that a response in the immune system causes the skin cells to grow quickly, resulting in plaques or lesions. These lesions are reddish and thick with silvery white scales that are loose and easily removed by scratching.(16,17)

The most common symptom associated with psoriasis is dry, flaky scaling of the skin, which is experienced by nearly 95% of patients. Itching and skin redness are the other two most prominent symptoms.(18)

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Wyeth Pharmaceuticals markets ENBREL outside North America. ENBREL was discovered by Immunex, now part of Amgen (NASDAQ: AMGN), and jointly developed with Wyeth Pharmaceuticals. The two companies co-promote ENBREL in North America.

Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, cardiovascular disease, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products. Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and nonprescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare, and Fort Dodge Animal Health.

1. Elewski B, Strober B, Tyring S, et al. Etanercept 50 mg once weekly sustains safety and efficacy for 96 weeks in plaque psoriasis patients. 15th Congress, European Academy of Dermatology and Venereology, 4-8 October 2006. Poster 950757

2. Data on file, Wyeth Pharmaceuticals, Inc.; Clinical Study Report 20030115. Final report: an open-label, long-term extension study to assess the safety of etanercept in the treatment of psoriasis in adult subjects. 28 November 2005

3. Enbrel Summary of Product Characteristics/Patient Information Leaflet, Wyeth Pharmaceuticals

4. Data on file, Wyeth Pharmaceuticals, Inc.; IMS Health, MIDAS via Dataview Analyzer, 4Q05, based on audited sales

5. Draft SmPC for PFS

6. Data on file, Amgen. Clinical Study Report 20030117. A phase 3 multicenter study to assess the efficacy and safety of etanercept 50 mg twice weekly in psoriasis. 24 February 2006

7. Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349:2012-2020

8. Gottlieb AB, Gordon KB, Weng AT, et al. Etanercept can safely be withdrawn from patients with psoriasis and re-establishes disease control on retreatment. Poster presented at the 10th International Psoriasis Symposium; June 10-13, 2004; Abstracts: 110-111; Toronto, Canada

9. Humira Summary of Product Characteristics, Abbott Laboratories

10. Raptiva Summary of Product Characteristics, Genentec Inc/Serono

11. Remicade Summary of Product Characteristics, Centocor Pharmaceuticals

12. Data on file, Wyeth Pharmaceuticals Inc.; Clinical Study Report 56504. A comparative pharmacokinetic study to compare subcutaneous (SC) administration of two 25-mg reconstituted etanercept injections to a single SC 50-mg liquid etanercept injection in healthy volunteers: final report. 12 May 2004

13. Wyeth Pharmaceuticals, Inc. ENBREL (etanercept) Core Claims Directive, Psoriasis: 2004. 2006 Version3

14. Christophers E. Psoriasis-epidemiology and clinical spectrum. Clin Exper Derm. 2001;26;314-320

15. Lebwohl M. Psoriasis. Lancet. 2003;361:1197-1204

16. Fitzpatrick TB, Johnson RA, Wolff K, et al. Psoriasis and ichthyosiform dermatoses. In: Color Atlas and Synopsis of Clinical Dermatology: Common and Serious Diseases. 4th ed. New York, NY: McGraw-Hill;2001;50-83

17. Peters BP, Weissman FG, Gill MA. Pathophysiology and treatment of psoriasis. AM J Health-Syst Pharm. 2000;57:645-659

18. Krueger G, Koo J, Lebwohl M, et al. The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey. Arch Dermatol. 2001;137:280-284

For further information please visit:
http://www.wyeth.com

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