Unique Three-Year Data Demonstrating Long-Term Efficacy and Safety of Raptiva in the Treatment of Psoriasis Published in the British Journal of Dermatology

• Longest continuous-treatment prospective study of a biological therapy for psoriasis

GENEVA, Switzerland, May 5, 2008 – Final results of the first three-year prospective efficacy and safety study in moderate-to-severe chronic plaque psoriasis were recently published in the British Journal of Dermatology1. They demonstrate the sustained safety and efficacy obtained with Raptiva® (efalizumab) in the long-term three-year therapy of this chronic autoimmune disease.

The data show that Raptiva® therapy had a sustained effect in those patients who responded to the initial 12-week treatment (82 %). A 75 % improvement in the disease, as measured by the standard Psoriasis Area and Severity Index (PASI) score (PASI-75), was achieved in 73 % of responders (as-treated analysis) after three years of continuous therapy2. Raptiva® was generally well tolerated during the treatment period of up to three years.

“No efficacy and safety studies of similar duration for biological psoriasis treatments have ever been published. The long-term use of traditional therapies may be limited by inconvenience, as in the case of phototherapy, or increased toxicities, for example with ciclosporin or methotrexate,” said study investigator Craig L. Leonardi, MD, Clinical Professor of Dermatology at Saint Louis University. “Efalizumab demonstrated sustained long-term efficacy and a favorable safety profile in this three-year trial. These features make it appropriate for continuous, long-term treatment of plaque psoriasis.”

“We see a positive benefit-risk-profile for Raptiva®. The results of this unique study indicate the efficacy of Raptiva® in this indication as well as its stable long-term safety profile,” added Anton Hoos, MD, Merck Serono’s Head of Global Development. “This is important and reassuring information for chronic psoriasis patients and their physicians who wish to manage the disease with continuous treatment.”

The objective of the study was to evaluate the efficacy and safety of long-term, continuous Raptiva® therapy in patients with psoriasis. This open-label, multicenter Phase III trial enrolled 339 adult patients with moderate-to-severe chronic (? six months) plaque psoriasis. During the initial three-month phase, patients received Raptiva® by subcutaneous injection (2 mg/kg/week). The second phase was a long-term observational period: Patients achieving at least 50 % improvement in PASI score (PASI-50) were eligible to receive Raptiva® (1 mg/kg/week) for up to 33 months; patients who had a relapse during months 4–15 ended participation in the current three-month segment and started the next segment at an escalated dosage of 2–4 mg/kg/week. The final three-month treatment period (months 34–36) was an optional transition period for patients who completed the 33-month segment before Raptiva® became commercially available.

Of the 290 patients who entered the observational period, 146 patients completed up to 33 months of Raptiva® treatment and were included in the as-treated analysis. A total of 108 patients received up to three years of Raptiva® therapy during the study (included in as-treated analysis). After the first three months of therapy, 82 % of all patients (n=339) had achieved PASI-50 or higher (41 % PASI-75, 13 % PASI-90). After three years of treatment, the as-treated analysis (n=113) resulted in a response rate of 73 % for PASI-75 (40 % PASI-90).

Raptiva® was generally well tolerated throughout three years of continuous treatment, with no evidence of cumulative or end-organ toxicity. Common adverse events (? 5 % of patients in any three-month segment) during long-term treatment included increased cough, rhinitis, sinusitis, and nonspecific infection (e.g. colds). There was no increase over time in the rate of those common adverse events. Likewise, no novel adverse events or increase in the overall incidence of adverse events or serious adverse events was noted over time. The relatively small size of the cohort limits the conclusions that can be drawn regarding rare events. A low proportion of patients (? 3.1 %) withdrew due to an adverse event during each three-month treatment segment of the observational period.

Footnotes
1C. Leonardi et al., “Efalizumab: results of a 3-year continuous dosing study for the long-term control of psoriasis”, British Journal of Dermatology 2008, 158, 1107-1116.
2All long-term efficacy claims refer to responding patients (“as treated” analysis). Only the patients who remain on therapy are taken into account, not those who discontinue treatment due to an adverse event, lack of efficacy, or any other reason.


About Raptiva®
Raptiva® (efalizumab) is a humanized therapeutic antibody designed to selectively and reversibly block the activation, reactivation and trafficking of T-cells that are critically involved in the psoriatic skin inflammation. 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”. Common adverse events observed with Raptiva® include headache, infections (e.g., common cold), chills, pain, nausea, asthenia (weakness), and fever, which usually diminish after the initial doses. For complete information on the safety profile of Raptiva®, the patient information leaflet should be consulted.

Raptiva® safety data have now been accumulated from ten years of clinical development and post-marketing experience in psoriasis patients. Raptiva® is a medicinal product subject to medical prescription. Treatment with Raptiva® should be initiated by a physician specialized in dermatology. The Marketing Authorization Holder of Raptiva® in the European Union is Serono Europe Ltd, an affiliate of Merck Serono S.A. The full Summary of Product Characteristics (SPC) for Raptiva® is available on http://www.emea.europa.eu/humandocs/Humans/EPAR/raptiva/raptiva.htm

Merck Serono has the rights to develop and market Raptiva® worldwide outside of the United States and Japan. To date, Raptiva® is available in 65 countries, amongst them many countries in Europe, Latin America, Asia as well as Australia and Canada. Raptiva® is licensed from Genentech, Inc., and Genentech retains development and marketing rights in the United States, where Raptiva® has been available since November 2003.

About Psoriasis
Psoriasis is a T-cell mediated disease, which is characterized by abnormal cell growth of keratinocytes and chronic inflammation clinically visible as thick, red, scaly, inflamed patches and plaques. Plaque psoriasis, the most common form of the disease, is characterized by sharp-edged inflamed patches of skin ("lesions") topped with silvery white scales. Psoriasis can be limited to a few spots, typically knees and elbows, but can also involve extensive areas of the body. 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 permanent cure.

About Merck Serono
Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American business operates in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), endocrine and cardiometabolic disorders (Glucophage®, Concor®, Saizen®, Serostim®), as well as psoriasis (Raptiva®).
With an annual R&D investment of around € 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

About Merck
Merck is a global pharmaceutical and chemical company with total revenues of EUR 7.1 billion in 2007, a history that began in 1668, and a future shaped by 31,681 employees in 60 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

For more information, please visit www.merckserono.net or www.merck.de

Posted: May 2008

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