Safety summary, FDA analysis, briefing document for Raptiva. I don't see any show stoppers, but this is a first-blush after about 120 seconds of assessment.......
fda.gov
Safety Assessments:
No deaths in psoriasis trials have been linked causally to the use of efalizumab.
Malignancies in the first exposure, placebo controlled portion of trials were few (n=4) and were not higher in in efalizumab-treated patients relative to control or to external cohorts. However, the numbers of cases are too small to make any definitive conclusions with regard to cancer risk.
There is no apparent increase in the incidence of NMSC in efalizumab-treated patients compared to placebo. However, the numbers are too small to assess the potential for increased risk due to efalizumab.
Serious infections have been reported in the first exposure of controlled clinical trials in a higher proportion of efalizumab-treated patients than placebo (0.4% vs. 0.1%). One opportunistic infection was observed, Legionella pneumonia. Other serious infections have consisted of severe local infections complicated by sepsis and seeding of distal sites.
Of the 2589 subjects treated with SC efalizumab,19 (0.7%) had a serious adverse event of psoriasis (including psoriatic erythroderma and pustular psoriasis). In the first exposure of controlled clinical trials of efalizumab, adverse events of psoriasis occurred in more subjects receiving efalizumab (2.4%, n=22) than placebo (1.1%, n=5).
Thrombocytopenia consisting of platelets < 50,000 cells/cmm occurred in a total of 8 efalizumab-treated patients. Clinical response to treatment with systemic corticosteroids suggests an immune-mediated thrombocytopenia. One patient had clinically significant bleeding requiring hospitalization.
Rare cases of serious inflammatory and/or potentially autoimmune events (e.g. transverse myelitis, pneumonitis, idiopathic hepatitis, serum sickness) have occurred in efalizumab-treated patients.
Laboratory abnormalities
Inflammation-associated laboratory analytes were higher in efalizumab-treated patients as compared to placebo. These included C reactive protein, fibrinogen and C3a and C5a.
Hematologic changes included increases in mean total white blood cell counts, approximate doubling of mean lymphocyte counts and smaller degrees of elevations in absolute eosinophil and neutrophil counts.
Elevations in alkaline phosphatase levels which are mostly unassociated with elevations in other hepatic tests. Both the intestinal and hepatic fractions are shown to be elevated.
Efalizumab has been associated with anti-human antibody (HAHA) in 6.3% of patients. There is no apparent decrease in clinical efficacy associated with HAHA positivity. The clinical significance with regard to safety is under investigation. |
