Pharmaceutical-Approval Update: Alefacept (Amevive®)

20 Jun
2010

Manufacturer: Biogen, Inc., Cambridge, MA Indication: Alefacept is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. Drug Class: 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. The drug’s molecular weight is 91.4 kd. Uniqueness of Drug: Alefacept therapy offers the first biological treatment approved for adults with moderate to severe chronic plaque psoriasis.

Warnings Lymphopenia

Alefacept induces dose-dependent reductions in circulating CD4+ and CD8+ T-lymphocyte counts. A course of alefacept therapy should not be initiated in patients with CD4+ T-lymphocyte counts below normal. The CD4+ T-lymphocyte counts of patients receiving alefacept should be monitored weekly throughout the course of the 12-week dosing regimen. Dosing should be withheld if CD4+ T-lymphocyte counts are below 250 cells per microliter (cells/ul), and therapy should be discontinued if the counts remain below 250 cells/ul for one month.

In clinical studies, patients who received alefacept therapy appeared to be at risk for the development of malignancies. In preclinical studies, B-cell hyperplasia occurred in animals, with a lymphoma developing in one animal. Alefacept should not be administered to patients with a history of systemic malignancy. Prescribers should exercise caution when considering the use of alefacept in patients at high risk for malignancy. If a malignancy develops, alefacept administration should be discontinued. Infections

Alefacept is an immunosuppressive agent and thus has the potential to increase the risk of infection and to reactivate latent, chronic infections. It should not be administered to patients with clinically serious infections. Prescribers should exercise caution when considering the use of alefacept in patients with chronic infections or a history of recurrent infection.

Patients should be monitored for signs and symptoms of infection during or after a course of alefacept. New infections should be closely monitored. If a serious infection develops, alefacept therapy should be discontinued.

Precautions Effects on the Immune System

Patients receiving other immunosuppressive agents or phototherapy should not receive concurrent therapy with ale-facept because of the possibility of excessive immuno-suppression. The length of the period before one considers starting other immunosuppressive therapy after treatment with alefacept has not been evaluated.
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In a study of 46 patients with chronic plaque psoriasis, the ability to mount immunity to tetanus toxoid (recall antigen) and an experimental neoantigen was preserved in those patients who were undergoing alefacept therapy. Allergic Reactions

Hypersensitivity reactions (urticaria, angioedema) were associated with the administration of alefacept. If an anaphy-lactic reaction or other serious allergic reaction occurs, administration of alefacept should be discontinued immediately and appropriate therapy should be initiated. Information for Patients

Patients should be informed that:

  • regular monitoring of white blood cell (lymphocyte) counts is required during therapy.
  • alefacept must be administered under the supervision of a physician.
  • alefacept therapy results in a reduced lymphocyte count, which might increase the risk of infection or malignancy.

Women of childbearing age make up a considerable segment of the patient population that is affected by psoriasis. Because the effect of alefacept on pregnancy, fetal development, and immune system development is unknown, health care providers are encouraged to enroll patients who are currently taking alefacept and who become pregnant into the Biogen Pregnancy Registry. Women should also be advised to notify their physicians if they become pregnant while taking ale-facept (or within eight weeks of discontinuing alefacept) and should be encouraged to enroll in the Pregnancy Registry.

CD4+ T-lymphocyte counts should be monitored weekly during the 12-week dosing period and should be used to guide dosing. Patients should have normal CD4+ T-lymphocyte counts before an initial or a subsequent course of treatment with alefacept. Dosing should be withheld if CD4+ T-lympho-cyte counts are below 250 cells/ul. Alefacept should be discontinued if CD4+ T-lymphocyte counts remain below 250 cells/ul for one month.
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Dosage: Alefacept should be used only under the guidance and supervision of a physician. The recommended dose is 7.5 mg, given once weekly as an intravenous bolus or 15 mg given once weekly as an intramuscular injection. The recommended regimen is a course of 12 weekly injections. Re-treatment with an additional 12-week course may be initiated if CD4+ T-lym-phocyte counts are within the normal range and a minimum of a 12-week interval has passed since the previous course of treatment. Data on re-treatment beyond two cycles are limited.

The CD4+ T lymphocyte counts of patients receiving ale-facept should be monitored weekly before dosing has begun and throughout the course of the 12-week regimen. As stated previously in this article, dosing should be withheld if these counts are below 250 cells/ul and the drug should be discontinued if the counts remain below 250 cells/ul for one month. P&T Committee Considerations: Psoriasis, which stems from a rapid runaway autoimmune response in the skin, causes skin itching, redness, flaking, pain, and cracking in about 2% of the population, or 5.5 million people, each year. The availability of alefacept may improve treatment of the disease, which currently relies on broad-based anti-inflammation techniques with limited effectiveness or with side effects.

Alefacept is the first drug from the biotechnology industry to treat this debilitating skin ailment. Approximately 1.5 million American adults have moderate to severe psoriasis. Ale-facept directly affects psoriasis-related inflammation through a specific immune-blocking action without undercutting the rest of the immune system and its ability to fight infection. It relieves symptoms during treatment and may spur remission. A pooled safety profile of alefacept, based on the results of three placebo-controlled trials that included 1,289 patients with chronic plaque psoriasis, showed that alefacept was well tolerated in psoriasis patients and had a safety and tolerability profile comparable to that of placebo. Nevertheless, the label’s warnings and precautions suggest that alefacept should be used with caution and that methotrexate should be the initial treatment of psoriatic patients with moderate and severe disease. Patients should be advised to inform their physicians promptly if any signs of an infection or malignancy occur while they are undergoing a course of treatment with alefacept. kamagra soft tablets

The manufacturer will be selling the drug to wholesalers for about $7,000 to $10,000 for a 12-week course of treatment. Patients and insurers are likely to pay about $8,400 to $11,900, a price that is less than the cost of methotrexate ($1,000 to $2,000 per year). The drug can be taken orally.

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