GD — Society for Dermopharmacy

Issue 1 (2004)

Dermopharmacy News
T-Lymphocyte-modulator Efalizumab
New therapy option at medium-severe to severe psoriasis

Numerous tests point to the fact that primarily immunological causes are responsible for the formation of psoriasis. In this connection activation and proliferation of T-lymphocytes are vitally important. The new T-lymphocyte modulator Efalizumab intervenes in this process thus allowing a swift and lasting control of skin manifestations. Controlled studies comprising more than 3.000 patients have proven that mainly persons suffering from medium-severe to severe psoriasis benefit from this highly effective systemic immunotherapy. Presumably Efalizumab will be available in the course of this year in Germany.

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Efalizumab is a recombinant humanized monoclonal anaphylactic which had been systematically developed to block the adhesion of T-lymphocytes at target cells. By bonding to the CD11a-surface antigen of the T-lymphocyte, Eflizumab inhibits several steps of the immunological cascade taking place in the case of illness, i. e.

the primary activation of T-lymphocytes,

the migration of T-lymphocytes into skin lesions and

the interaction of T-lymphocytes with keratinocytes.

In this manner, inflammatory processes are stopped and a normalization of the interfered differentiation and proliferation of keratinocytes comes about. Whereas present therapy approach aimed at oppressing the immune system by different methods, Efalizumab intervenes for the first time systematically in immunological processes.

Clinical picture improved at
extended duration of treatment

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Effectiveness, safety and tolerance of Efalizumab have been investigated in four randomized, double-blind, placebo-controlled phase III studies. The effectiveness of the product in a dose 1 mg/kg weight has been compared with placebo in the process of a study encompassing 1.242 patients. For this aim, Efalizumab and placebo have been injected once a week subcutaneously.

First improvements of the skin complexion already showed after two weeks. Psoriasis area and severity index (PASI) had improved for 56 percent of the patients by at least 50 percent, for 28 percent of the patients even by at least 75 percent after twelve weeks.

In a second step of the study patients received either Efalizumab or placebo depending on the therapy success for additional twelve weeks. The therapy success persisted for 77 percent of the patients in a group with extended administration of the active agent whereas this has been the case for only 20 percent in the placebo group. The pathology gradually returned to the initial value in all groups after termination of the therapy. However, one third of the patients who had been treated with Efalizumab for 24 weeks still showed an improvement by over 50 percent of the PASI in comparison to the initiation of the study even after 36 weeks.

In an open long-term study scheduled for three years, effectiveness and tolerance of Efalizumab had been tested at 290 patients. The dose administered was at 1mg/kg weight per week with the option to individually increase the dose to up to 4 mg/kg weight per week. In the course of the first six months more than the majority of the patients experienced an improvement of the PASI by at least 75 percent, 22 percent even observed an improvement by at least 90 percent. After 21 months the percentage of the patients who attained an at least 75 percent amelioration increased to 64 percent. 31 percent of the patients even realized a 90 percent improvement.

Improvement of quality of life
and good tolerance

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The administration of the product once a week offers significant advantages in view of the compliance: the injection is easily learnable for the patient and practicable in every-day life. Furthermore, formation of tolerances has not been observed so far.

The side-effect profile of Efalizumab is particularly favourable. Symptoms similar to influenza such as headache, fever and ague, nausea, and algiomuscular pain may develop. These side effects, however, appeared acutely only at the first two injections and abated in the aftermath in most cases. According to the present experience with Efalizumab there is no indication to an immunosuppression and an increased tumour risk.

Efalizumab will presumably be available in Germany this year. The application of registration was filed on 26 February 2003 with the European Authorization Administration EMEA. Efalizumab is already marketed in the USA, Switzerland and several other countries under the name Raptiva®. Producer is the company Serono, the third-largest biotechnological company of the world. The seat of the company in Germany is located in Unterschleißheim near Munich.

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October 2004