Source: Cornea  |  Posted 5 years ago

Extended Therapy Maintains and Improves Clinical Responses

GENEVA, SWITZERLAND -- October 31, 2006 -- Serono (virt-x: SEO and NYSE: SRA) announced today that the 24-week data from the clinical study CLEAR (CLinical Experience Acquired with Raptiva(r)), evaluating moderate-to-severe psoriasis patients, as well as refractory patients, was published in this month's edition of the Journal of the German Society of Dermatology.[1]

The data confirms the efficacy and safety of Raptiva(r) seen during the initial 12-week treatment period and demonstrates a continued improvement in clinical response for patients following an extended treatment. Also, Raptiva(r) was found to be equally effective in the subgroup of patients refractory to at least two systemic therapies compared to the overall moderate-to-severe patient population. Refractory patients had suffered from psoriasis for a longer time, had a more severe disease and a greater past history of co-morbidities, such as psoriatric arthritis, hypertension, metabolic and nutritional disorders, and hepatobiliary disorders[2].

"Extended treatment with Raptiva(r) resulted in a sustained clinical improvement for psoriasis patients, including refractory patients who had a significant high unmet medical need," said Professor Wolfram Sterry, Director of the Department of Dermatology, Venerology and Allergology at the University Hospital Charit? Berlin, Germany. "These patients did not respond to or could not take traditional therapies and had in many cases additional co-morbidities."

The aim of the CLEAR study was to evaluate the efficacy and safety of Raptiva(r) compared to placebo in patients who either continued after an initial 12-week therapy to receive treatment up to 24 weeks, or who received re-treatment for an additional 12 weeks following a treatment-free observation period.

Key Study Findings:

After 12 weeks of treatment, Raptiva(r) met its primary endpoint and showed a favourable safety and efficacy profile with a statistically significantly higher PASI 75 rate[3] demonstrating clinical superiority over placebo:

- 31.4% of patients treated with Raptiva(r) in the overall, non-refractory patient population (267/793) reached a ? 75% PASI improvement compared to 4.2% of those treated with placebo (p < 0.0001)

- 29.5% of patients treated with Raptiva(r) in the refractory patient group (526/793) reached a PASI 75 rate compared to 2.7% of those treated with placebo (p < 0.0001).

After 24 weeks of treatment, the results of the CLEAR study confirm the efficacy and safety of Raptiva(r) demonstrated in the initial 12-week treatment period:

- Following the extended treatment period, 47.5% of patients with an initial PASI improvement of ? 50% but < 75% at week 12 continued to improve over time and achieved PASI 75

- Median time to relapse during the observation period was 58 days for patients who achieved a PASI 75 response after an initial 12-week treatment with Raptiva(r)

- The safety profile of Raptiva(r) is consistent with previous experience and no new safety concerns were identified

"For psoriasis patients often requiring a lifelong treatment, these results are encouraging and demonstrate that Raptiva(r) provides an innovative, effective and safe treatment paradigm for a continuous management of the chronic disease." said Professor Sterry.

CLEAR is the only multinational, randomized, double-blind, placebo-controlled, parallel-group trial demonstrating the efficacy of a biological therapy in an international refractory patient population, where other systemic therapies were inappropriate due to contraindications or intolerance, or where patients failed to respond to them. CLEAR prospectively and uniquely demonstrates that Raptiva(r) is an effective therapy in moderate-to-severe plaque psoriasis patients regardless of previous systemic treatments.

In North-American studies, Raptiva(r) was also demonstrated to be equally effective in overweight patients, another common co-morbidity with psoriasis[4].

Globally, more than 30,000 patients have received Raptiva(R), both during clinical trials and post registration. This represents more than 22,500 patient years of exposure, creating one of the largest existing databases of patients taking a biological therapy for psoriasis. About the CLEAR Study

CLEAR (CLinical Experience Acquired with Raptiva(r)) is the first multinational, randomized, double blind, placebo-controlled, parallel-group trial designed to evaluate the safety and efficacy of Raptiva(r) compared to placebo. Patients with moderate-to-severe plaque psoriasis, including refractory patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication, were randomized in a 2:1 ratio to receive either once weekly for 12 weeks 1mg/kg Raptiva(r) or placebo. 793 patients were included in this prospective trial, thereof 529 were randomized to Raptiva(r) and 264 to placebo. Amongst the 793 patients, 526 were refractory patients.

The CLEAR trial comprised four discrete periods: a double-blind, first treatment (FT) period, in which patients were randomized 2:1 to Raptiva(r) or placebo for 12 weeks; an observation (OB) period, in which those patients who achieved a PASI-75 response were observed, without treatment, for up to 24 weeks or until they had a relapse; an open-label, re-treatment (RT) period, in which, following relapse or completion of the OB period, patients were re-started on open-label treatment with Raptiva(r) for 12 weeks; and an open-label, extended-treatment (ET) period, in which patients who did not achieve a PASI 75-response at the end of the FT period continued to receive open-label treatment with Raptiva(r) for up to 24 weeks without intervening OB period.

The primary endpoint of the CLEAR study was to evaluate the safety and efficacy of Raptiva(r) 1mg/kg given subcutaneously once a week for 12 weeks compared to placebo. The secondary endpoint was to evaluate the safety and efficacy of Raptiva(r) during the extended treatment, observation and re-treatment periods.

Overall, the safety profile of Raptiva(r) in the CLEAR study is consistent with that reported in previous US phase III clinical studies and no new safety concerns were identified. The most frequent adverse events were consistent with the syndrome of 'acute adverse events' known to be associated with initial Raptiva(r) treatment, including headache, chills, fever, nausea, or myalgia occurring within 48 hours of injection.

Full data on the initial 12-week treatment period has been published in the British Journal of Dermatology in June 2006.[5]

About Raptiva(R)
Raptiva(R) (efalizumab) 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(R) is designed to be administered once weekly via subcutaneous injection and can be self-administered by patients at home.

Raptiva(R) 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 cyclosporine, methotrexate and PUVA'.

Adverse events observed with Raptiva(R) include headache, non-specific infection (e.g., common colds), chills, pain, nausea, asthenia (weakness), and fever, all of which diminished after the first 1-2 doses. There is no evidence of accumulation or cumulative toxicity to date.

Serono has the rights to develop and market Raptiva(R) worldwide outside of the United States and Japan. To date, Raptiva(r) is available in over 50 countries, amongst them many countries in Europe, Latin America, Asia as well as Australia. Development and marketing rights in the United States, where Raptiva(r) has been available since November 2003, remain with Genentech, Inc.

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 permanent cure.

REFERENCES:
[1] Sterry et al., Clinical Experience Acquired with Raptiva (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from extended treatment in an international, Phase III, placebo-controlled trial, JDDG Vol. 4, Issue 11, Page 947, November 2006
[2] Prinz JC, Henninger E, Patient Characteristics and Drug Exposure in High-Need Patients: The CLEAR Experience, EADV Spring Symposium, Sofia, Bulgaria, May 2005, Poster
[3] Psoriasis Area and Severity Index; most commonly used clinical scoring system to assess disease severity in clinical trials
[4] Lebwohl M. et al., Efficacy and Safety of efalizumab in patients with high body weight: pooled results from randomized phase III trials, Summer AAD 2005, Chicago, USA, Poster
[5] Dubertret L, Sterry W, Bos JD, Chimenti S, Shumack S, Larsen CG, Shear NH, Papp KA, CLEAR Multinational Study Group. Clinical Experience acquired with the efalizumab (Raptiva) CLEAR trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial. Br J Dermatol 155:170-181

SOURCE: Serono International S A