Long Term Benefit Of Continuous Treatment With Raptiva In Responding Psoriasis Patients

Main Category: Eczema / Psoriasis
Article Date: 13 Oct 2005 - 16:00 PDT

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Serono announced today data from the CLEAR trial presented at the 14th European Academy of Dermatology and Venerology (EADV) Congress in London showing that 47.5% of patients, who achieved PASI 50 after 12 weeks Raptiva� treatment, achieved a 75% or greater improvement in the Psoriasis Area Severity Index (PASI 75) with extended Raptiva� therapy to 24 weeks (total treatment period of 24 weeks). Furthermore, over 40% of patients with a PGA (Physician Global Assessment) rating of 'good' after 12 weeks of treatment, achieved a rating of 'excellent' or 'cleared' with extended treatment to 24 weeks. These results confirm the long-term benefit of continuous therapy with Raptiva in responding patients.

"Biological treatments give us new hope of providing psoriasis patients with improved therapies that will be easier to manage" said Prof. Dr. Wolfram Sterry, Director of the Clinic of Dermatology, Venereology and Allergology at the Charit� in Berlin & past-President of the DDG (German Dermatological Society). "Raptiva� has a favorable benefit-risk profile during continuous therapy in responders and should be considered as one of the best choice biological treatments for moderate-to-severe psoriasis."

The multi-center, multi-national CLEAR trial evaluated the safety and efficacy of Raptiva� in patients with moderate-to-severe psoriasis. Extended treatment of Raptiva� patients who did not attain PASI 75 response with 12 weeks of therapy resulted in maintenance and improvement of response. Notably, among the Raptiva� patients who showed _50% but �75% improvement after 12 weeks, nearly half had attained a PASI 75 response at the end of extended treatment. Among Raptiva� patients who had a PGA rating of 'good' at week-12, 43.9% had attained a rating of 'excellent' or 'cleared' by the end of the extended 24-week treatment period. The safety profile of Raptiva� in this study was consistent with previous experience and no new safety concerns were identified with continued treatment or retreatment. There were no reports of demyelinating disorders, pancytopenia, tuberculosis or congestive heart failure.1

Results of the CLEAR study support Raptiva� as a valuable option for treatment of adults with chronic plaque psoriasis for whom other systemic treatments are unsuitable due to contraindication, intolerance or lack of efficacy. Raptiva is licensed for this group of patients in the EU.

*Prescribing Information on last page. Date of preparation: October 2005. Job number: D350905 Further Australian post-marketing observational study data presented at the 14th EADV Congress by Dr Peter Foley from the Department of Dermatology at St Vincent's Hospital, Melbourne, Australia, showed a favorable response in 102 patients with severe chronic plaque psoriasis receiving Raptiva�. Results revealed that 75% of patients achieved PASI 50 improvement following 12 weeks of treatment, while 45% achieved PASI 75 and 27% achieved PASI 90.2

Previously, a 3-year, phase IIIb open-label study performed in North America also evaluated the long-term safety and efficacy of continuous treatment with Raptiva� in moderate-to-severe psoriasis patients. At the end of the final period of this trial, 73% of patients (82/113) who remained on therapy demonstrated a sustained clearing of psoriasis symptoms achieving PASI 75 and 40% of patients achieving PASI 90. Raptiva� was generally well tolerated throughout 36 months of continuous treatment with no cumulative end-organ toxicity or increased malignancy or infection. No increase in overall incidence of adverse events was seen during long-term therapy.3

About Raptiva�

Raptiva� is a humanized therapeutic antibody designed to selectively and reversibly block the activation, reactivation and trafficking of T-cells that lead to the development of psoriasis symptoms. Raptiva� is designed to be administered once weekly via subcutaneous injection and can be self-administered by patients at home.

Raptiva� received EU approval for the 'Treatment of adult patients with moderate to severe chronic plaque psoriasis who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporine, methotrexate and PUVA'.

Serono has the rights to develop and market Raptiva� worldwide outside of the United States and Japan. To date, Raptiva� has been approved in over 40 countries, amongst them many countries in Europe, Latin America, Asia as well as Australia. Development and marketing rights in the United States, where Raptiva� has been available since November 2003, remain with Genentech Inc. (NYSE:DNA) and its U.S. partner XOMA (Nasdaq: XOMA).

More than 3,500 patients in the U.S. and Europe have been included in Raptiva� trials to date, creating the largest existing database of patients taking part in studies with a biological therapy for psoriasis.

About the CLEAR Study In this prospective, multicenter, multi-national study, a total of 793 patients were recruited and randomized in a 2:1 ratio to either Raptiva� treatment or placebo for 12 weeks (first treatment period). After 12 weeks, patients achieving >= 75% improvement in the Psoriasis Area and Severity Index (PASI 75) were observed either until they relapsed or for a maximum of 24 weeks (observation period). Patients then started treatment with Raptiva� for 12 weeks (re-treatment period) and were followed for a further 8 weeks (follow-up period). Those patients who achieved a score between <= PASI 50 and >= PASI 75 after the initial 12 weeks of treatment received Raptiva� for a 12-week extended treatment (extended treatment phase). These patients were then observed for an 8-week follow-up period.

In all study periods, the majority of reported adverse events were mild to moderate in severity.

About the Australian Regional study

A total of 102 patients were with severe chronic plaque psoriasis were reviewed following 12 and 24 weeks of therapy with Raptiva� while taking their routine systemic therapy. Criteria for receiving Raptiva� were previously documented treatment with at least 2 systemics including methotrexate or ciclosporine; and a PASI greater than 15 prior to commencing treatment with Raptiva�. PASI score at 12 and 24 weeks were compared to baseline PASI.

About the 36-month phase IIIb open-label study

This three-year study is the longest study of psoriasis patients receiving continuous treatment with a biologic treatment. In this study, 339 patients received Raptiva� weekly for an initial 12 weeks, and patients with a PASI 50 response or a static Physician's Global Assessment response of 'mild' or 'better' after 12 weeks of treatment were eligible to continue on a once-weekly maintenance dose of 1 mg/kg Raptiva� for 12-week periods starting at week 13. A total of 290 subjects entered this second phase of the study. For each successive three-month period of treatment, dropouts during that period were analyzed using their last available PASI assessment but were excluded from the subsequent cohorts.

The full results of this study were presented at the American Association of Dermatology ACADEMY 2005 meeting in New Orleans.

About Psoriasis

Psoriasis is a T-cell mediated disease, which occurs when skin cells grow abnormally, resulting in thick, red, scaly, inflamed patches. Plaque psoriasis, the most common form of the disease is characterized by inflamed patches of skin ("lesions") topped with silvery white scales. Psoriasis can be limited to a few spots or involve extensive areas of the body, appearing most commonly on the knees, elbows, trunk, and scalp. Although it is highly visible, psoriasis is not a contagious disease. While there are a number of medications that may help control the symptoms of psoriasis, there currently is no known cure.

Background material

For free B-roll, video and other content about Raptiva�, psoriasis and Serono, please visit the Serono Media Center http://www.thenewsmarket.com/Serono. You can download print-quality images and receive broadcast-standard video digitally or by tape from this site. Registration and video is free to the media.

About Serono

Serono is a global biotechnology leader. The Company has eight biotechnology products, Rebif�, Gonal-f�, Luveris�, Ovidrel�/Ovitrelle�, Serostim�, Saizen�, Zorbtive� and Raptiva�. In addition to being the world leader in reproductive health, Serono has strong market positions in neurology, metabolism and growth and has recently entered the psoriasis area. The Company's research programs are focused on growing these businesses and on establishing new therapeutic areas, including oncology. Currently, there are approximately 30 ongoing development projects.

In 2004, Serono achieved worldwide revenues of US$2,458.1 million, and a net income of US$494.2 million, making it the third largest biotech company in the world. Its products are sold in over 90 countries. Bearer shares of Serono S.A., the holding company, are traded on the virt-x (SEO) and its American Depositary Shares are traded on the New York Stock Exchange (SRA).

Some of the statements in this press release are forward looking. Such statements are inherently subject to known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements of Serono S.A. and affiliates to be materially different from those expected or anticipated in the forward-looking statements. Forward-looking statements are based on Serono's current expectations and assumptions, which may be affected by a number of factors, including those discussed in this press release and more fully described in Serono's Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on March 16, 2005. These factors include any failure or delay in Serono's ability to develop new products, any failure to receive anticipated regulatory approvals, any problems in commercializing current products as a result of competition or other factors, our ability to obtain reimbursement coverage for our products, the outcome of government investigations and litigation and government regulations limiting our ability to sell our products. Serono has no responsibility to update the forward-looking statements contained in this press release to reflect events or circumstances occurring after the date of this press release.

For more information, please contact:

Claire Payne
Director Brand Communications
Serono International
c.payne@serono.com

St�phanie Makin
Tonic Life Communications
+44 7769 673 973
stephanie.makin@toniclc.com

References
1. Ring J., Dubertret L., May T., Chimenti S. and Sterry W. The safety and efficacy of efalizumab in patients with chronic plaque psoriasis: results from retreatment and extended treatment phases following a placebo-controlled trial. EADV 2005, London poster P06.87
2. G. Varigos, E. Moore & P. Foley. A 6 month follow-up of 102 patients with severe chronic plaque psoriasis receiving a combined systemic therapy with efalizumab in Australia. EADV 2005, presentation Fco7.8
3. Gottlieb A.B., Gordon K.B., Hamilton T.K., Caro I., Kwon P., Compton P. and Leonardi C.L. Maintenance of Efficacy and Safety with Continuous Efalizumab Therapy in Patients with Moderate to Severe Chronic Plaque Psoriasis: Final Phase IIIb Study Results. AAD 2005 poster P4

PRESCRIBING INFORMATION

Raptiva � 100 mg/ml powder and solvent for solution for injection efalizumab

Presentation
Glass vial of powder containing 125 mg efalizumab, plus pre-filled syringe of water for injections.

Indications
Treatment of adult patients with moderate to severe chronic plaque psoriasis who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporine, methotrexate and PUVA.

Dosage and administration
Treatment with Raptiva should be initiated by a physician specialised in dermatology.

Subcutaneous injection. Initial single dose of 0.7 mg/kg body weight, followed by weekly injections of 1.0 mg/kg body weight (maximum single dose should not exceed a total of 200 mg). The volume to be injected:

Dose
Volume to be injected per 10 kg body weight
Single initial dose: 0.7 mg/kg
0.07 ml
Subsequent doses: 1 mg/kg
0.1 ml
The duration of therapy is 12 weeks. Therapy may be continued only in patients who responded to treatment (PGA good or better).
Not to be used in patients under 18 years of age.

Contraindications

Hypersensitivity to efalizumab or to any of the excipients.
History of malignancies.
Active tuberculosis and other severe infections.
Specific forms of psoriasis like guttate, erythrodermic or pustular psoriasis as sole or predominant form of psoriasis.
Immunodeficiencies.

Precautions

Raptiva may affect host defenses against infections. Raptiva should be used with caution in patients with history of clinically significant recurring infections. Infections during treatment should be monitored, and according to severity, Raptiva should be discontinued.

As there is a higher incidence of infections in the elderly population in general, caution should be used in treating the elderly.

Patients should not receive acellular, live and live-attenuated vaccines during Raptiva treatment.

Discontinue if a malignancy develops during treatment. Raptiva has not been studied in combination with immunosuppressive systemic antipsoriasis medicinal products. Therefore, combination therapies with these products are not recommended.

Thrombocytopenia may occur during Raptiva treatment and may be associated with clinical signs such as echymoses, spontaneous bruising or bleeding from muco-cutaneous tissues. If these signs occur, efalizumab should be stopped immediately, a platelet count should be performed and appropriate symptomatic treatment should be instituted immediately.

Platelet counts are recommended upon initiating and periodically while receiving Raptiva treatment.

Raptiva is potentially immunogenic. If any serious hypersensitivity or allergic reaction occurs, Raptiva should be discontinued immediately and appropriate therapy initiated.

If arthritis occurs during treatment Raptiva should be discontinued.

If exacerbation of psoriasis, including pustular, erythrodermic, and guttate subtypes, is seen, it is recommended to discontinue treatment with Raptiva.

Abrupt discontinuation of treatment may cause a recurrence or exacerbation of plaque psoriasis including erythrodermic and pustular psoriasis.

Use with caution in patients with renal or hepatic impairment.

Pregnancy and lactation
Raptiva should not be used in pregnant or lactating women, or women of childbearing potential without appropriate contraception.

Side effects

The most frequent adverse drug reactions (ADRs) are mild to moderate dose-related acute flu-like symptoms including headache, fever, chills, nausea and myalgia., which decrease in frequency after third and subsequent weekly injection.

An observation in up to 50% of patients is leukocytosis and lymphocytosis. In clinical studies, between 40 and 50% of patients developed sustained asymptomatic lymphocytosis during Raptiva therapy. These changes are consistent with the mechanism of action of efalizumab.

Common adverse events reported in clinical trials include psoriasis exacerbation, arthralgia, exacerbation/flare of psoriatic arthritis, hypersensitivity reactions, back pain, asthenia, elevation of alkaline phosphatase, elevation of ALT. Uncommon adverse events include thrombocytopenia, urticaria, and injection site reactions.

Pharmaceutical precautions
Store in a refrigerator ( 2_8�C) in the original package. Do not freeze. Use immediately after first opening and reconstitution.

Legal category POM

basic NHS price
Raptiva vial (125 mg efalizumab)- 1 vial �169.20

Marketing Authorisation numbers:
Raptiva vial - EU/1/04/291/001 (1 vial)

Name and Address of Distributor in UK
Serono Ltd
Bedfont Cross
Stanwell Road
Feltham
Middlesex
TW14 8NX
Tel. 020 8818 7200

Name and Address of Distributor in Ireland
Allphar Services Ltd
Pharmaceutical Agents and Distributors
Belgard Road
Tallaght
Dublin 24
Eire

Name and address of Marketing Authorisation Holder
Serono Europe Ltd
56 Marsh Wall
LONDON
E14 9TP

Date of Preparation: September 2005

Kristin O'Leary
Senior Account Executive
Tonic Life Communications Ltd
t +44 (0)20 7798 9913
f +44 (0)20 7233 8780
e kristin.o'leary@toniclc.com
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