Jane S. Ricciuti, RPh, MS

Disclosures

February 19, 2003

In This Article

Dermatologic Agents

Amevive
(alefacept) Injection

Manufacturer: Biogen, Inc.

Drug Approval Classification: BLA (approval date: 1/30/03)

Indication: Amevive (alefacept) is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.

Dosing: Alefacept is available as an intravenous or intramuscular injection:

Alefacept 7.5 mg given once weekly as an intravenous bolus or

  • Alefacept 15 mg given once weekly as an intramuscular injection.

  • The recommended regimen is a course of 12 weekly injections. Retreatment with an additional 12-week course may be initiated provided that CD4+ T lymphocyte counts are within the normal range, and a minimum of a 12-week interval has passed since the previous course of treatment. Data on retreatment beyond 2 cycles are limited.

    The CD4+ T lymphocyte counts of patients receiving alefacept should be monitored weekly before initiating dosing and throughout the course of the 12-week dosing regimen. Dosing should be withheld if CD4+ T lymphocyte counts are below 250 cells/microL. The drug should be discontinued if the count remains below 250 cells/microL for 1 month.

    Clinical Summary: 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 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.

    Alefacept was evaluated in 2 multicenter, randomized, double-blind, placebo-controlled studies in over 1000 patients for 12 weeks. Concomitant low-potency topical steroids were permitted during the study. Patients on alefacept intravenous (IV) injections experienced a superior response of 11% difference compared with placebo. A 15% difference was seen in alefacept intramuscular (IM) injections compared with placebo. The median time to response is 3 months with IV treatments and 2 months with IM treatments.

    The FDA approval letter for alefacept included an outline of ongoing and postmarketing studies to be completed and submitted to the FDA. It stated the following goals of these studies:

    To develop a dual-specificity immunogenicity assay for anti-LFA3TIP antibodies that is capable of distinguishing between anti-LFA3 and anti-Fc antibodies.

  • To test archival patient samples from all patients who tested positive for anti-LFA3TIP antibodies and a sampling of patients who tested negative for a total of approximately 1200 patient samples in the new dual-specificity immunogenicity assay.

  • To further assess the effect of body weight on the safety and efficacy of alefacept in a multicenter, randomized, blinded, parallel-group study of approximately 390 patients.

  • To further evaluate the safety and efficacy of alefacept when administered over multiple cycles. The study will include 400 patients treated with up to 3 courses of alefacept.

  • To further evaluate the risk of infections and malignancies in patients treated with alefacept in a single cohort of 5000 patients followed for 5 years.

  • To further evaluate the time course of recovery of lymphocyte counts (total lymphocytes and important lymphocyte subsets) to within 75% of baseline. The study will include 400 patients treated with up to 3 courses of alefacept.

  • To evaluate the safety and efficacy of alefacept in patients with erythrodermic and pustular psoriasis.

  • To report the results of study C-715 evaluating the safety and efficacy of alefacept in patients with concomitant psoriasis and psoriatic arthritis.

  • To provide an assessment of the potential need to study alefacept in the HIV population when more data on the long-term safety in the non-HIV-infected population becomes available.

  • To obtain additional safety data in populations with advanced age, diabetes mellitus, and major trauma (accidental or surgical).

  • To evaluate the safety of alefacept administered concomitantly with UVB and major systemic antipsoriatic therapies, methotrexate, and cyclosporine.

  • To establish and maintain a pregnancy registry of women with psoriasis who were exposed to alefacept at any point within an 8-week time period prior to conception, or at any point during the pregnancy.

  • Adverse Effects: Bolded warnings are highlighted in the alefacept labeling for the risk of lymphopenia. Patients with a CD4+ cell count below normal should not be started on therapy. During the 12-week regimen, patients' CD4+ cell counts should be monitored weekly.

    Malignancies were experienced by some patients in the alefacept clinical program (incidence < 1%). In preclinical studies, animals developed B-cell hyperplasia, and 1 animal developed a lymphoma.

    Due to the decrease in circulating T lymphocytes, there is the potential for serious infections.

    Alefacept is classified as Pregnancy Category B -- there have been no studies in pregnancy and fetal development. Healthcare providers are encouraged to enroll patients currently taking alefacept who become pregnant into the Biogen Pregnancy Registry (additional information is detailed in the Amevive labeling).

    Pharmacokinetics: The mean volume of distribution of alefacept following an IV 7.5-mg injection was 94 mL/kg, the mean clearance was 0.25 mL/h/kg, and the mean elimination half-life was approximately 270 hours. Following an IM injection, bioavailability was 63%.

    Circulating memory effector subsets of the CD4+ and CD8+ T lymphocyte compartments are lowered by alefacept.

    No drug-drug interaction studies have been performed.

    Amevive (alefacept) Labeling

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