Amevive (alefacept);新一代银屑病治疗药品治疗中重度慢性银屑病注射针剂

Amevive是美国Biogen公司生产制造的新一代银屑病治疗药品,在经历了数年的试验后,今年5月23日,在FDA举办的专家评议会上,十位专家以8票同意,2票反对的投票率通过了对它的审批。这是FDA有史以来第一次批准生物药品用于寻常型银屑病治疗。 

Product Code	Brand Name	Generic Name	Unit	Price	Class
3491917	Amevive IM			$1,013.00	O
3491933	Amevive IM 1x4			$4,055.00	O

简单说Amevive是一种生物药品,是蛋白质,与传统的化学制药制造出的具有严格化学分子式的小分子药品(比如维甲酸、环胞素、钙泊三醇等)完全不同。新型的生物药品制造出的药品都是蛋白质大分子,因为胃肠会把蛋白质分解为氨基酸,所以这一类通常只能通过注射方式给药,不能口服。生物药品的好处是可以作用于人体生命活动的某一个具体环节,比如amevive就是直接作用于人体免疫系统的T细胞,从而中断银屑病的发生过程。因此从原理上讲,它的副作用比化学药品要小,化学药品的作用范围一般都是全身性的。现在还有多种治疗银屑病的生物药品正处于研发和试验阶段,Amevive是这批药物中进入实用的第一个。可以预言,生物药品将是今后几年内国外银屑病科研及治疗的主要方向之一。

 在Amevive二期的临床试验过程中,曾引起了各方的关注,据称其有效率相当的高,可以接近60%。当然事物总有一个发展过程,作为第一种治疗寻常型银屑病的生物药品,它可能还有很多不足,对长期的副作用的担忧、价格等可能都会影响它的推广。

Drugs Approved by the FDA

The following information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: Biogen
Approval Status: Approved January 2003
Treatment for: Psoriasis

General Information

Amevive (alefacept) is an immunosuppressive dimeric fusion protein that reduces lymphocyte counts (T-cells) thus treating the cause of psoriasis. It is indicated in patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy

Amevive is available in either intramuscular injection (15-mg alefacept) or intravenous injection (7.5-mg alefacept) formulations.

Amevive reduces immune cell counts which could increase the chance of developing infection or malignancy.

Clinical Results

Amevive was evaluated in two randomized, double blind, placebo-controlled studies in 726 adult subjects with chronic plaque psoriasis. In both trials, Amevive or placebo was administered once a week for 12 weeks. In total 77% of subjects had previously received systemic therapy and/or phototherapy for psoriasis.

Response to treatment in both studies was defined as the proportion of subjects with a reduction in score on the Psoriasis Area and Severity Index (PASI)?of at least 75% from baseline at two weeks following the 12-week treatment period. Other treatment responses included the proportion of subjects who achieved a scoring of 'almost clear' or 'clear' by Physician Global Assessment (PGA) and the proportion of subjects with a reduction in PASI of at least 50% from baseline two weeks after the 12-week treatment period.

In both studies, onset of response to Amevive treatment (at least a 50% reduction of baseline PASI) began 60 days after the start of therapy. In Study 1, the median duration of response (75% or greater reduction in PASI) was 3.5 months for Amevive treated patients and 1 month for placebo-treated patients. In Study 2, the median duration of response was approximately 2 months for both groups. A majority of the subjects had responded to either Amevive or placebo maintained a 50% or greater reduction in PASI through the 3-month observation period. In both studies, an additional 11% (42/367) and 7% (12/166) of subjects treated with Amevive, respectively, achieved a 75% reduction from baseline PASI score at one or more visits after the first 2 weeks of the follow-up period.

Side Effects

Adverse events associated with the use of Amevive may include (but are not limited to) the following:

• Serious Infections

• Malignancies

• Lymphopenia

• Sore throat

• Dizziness

• Cough

• Nausea

• Itching

• Muscle Aches

• Chills

• Injection Site Pain

• Injection Site Inflammation

• Accidental injury

　

Mechanism of Action

Amevive (alefacept) is an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3 domains) portion of human IgG1. Alefacept is produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) mammalian cell expression system.

Amevive interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. The majority of T lymphocytes in psoriatic lesions are of the memory effector phenotype characterized by the presence of the CD45RO marker? express activation markers (e.g., CD25, CD69) and release inflammatory cytokines, such as interferon y.

Amevive also causes a reduction in subsets of CD2+ T lymphocytes (primarily CD45RO+), presumably by bridging between CD2 on target lymphocytes and immunoglobulin Fc receptors on cytotoxic cells, such as natural killer cells. Treatment with Amevive results in a reduction in circulating total CD4+ and CD8+ T lymphocyte counts. CD2 is also expressed at low levels on the surface of natural killer cells and certain bone marrow B-lymphocytes.

Literature References

Bos JD, Hagenaars C, Das PK, et al. Predominance of 'memory' T cells (CD4+, CDw29+) over 'na飗e' T cells (CD4+, CD45R+) in both normal and diseased human skin. Arch Dermatol Res 1989; 281:24-30.

Ellis C, Krueger GG. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001; 345:248-255.

Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica 1978; 157:238-244.

Additional Information

For additional information regarding Amevive or psoriasis, please contact