Clinical Trial Experience

Meningococcal infections are the most important adverse reactions experienced by patients receiving Soliris therapy. In PNH clinical studies, two patients experienced meningococcal sepsis. Both patients had previously received a meningococcal vaccine. In clinical studies among patients without PNH, meningococcal meningitis occurred in an unvaccinated patient [see WARNINGS and PRECAUTIONS].

The data described below reflect exposure to Soliris in 196 adult patients with PNH, age 18-85, of whom 55% were female. All had signs or symptoms of intravascular hemolysis. Soliris was studied in a placebo-controlled clinical study (in which 43 patients received Soliris and 44, placebo); a single arm clinical study and a long term extension study. 182 patients were exposed for greater than one year. All patients received the recommended Soliris dose regimen.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Table 1 summarizes the adverse reactions that occurred at a numerically higher rate in the Soliris group than the placebo group and at a rate of 5% or more among patients treated with Soliris.

TABLE 1

ADVERSE REACTIONS REPORTED IN 5% OR MORE OF SOLIRIS TREATED PATIENTS AND GREATER THAN PLACEBO IN THE CONTROLLED CLINICAL STUDY

In the placebo-controlled clinical study, serious adverse reactions occurred among 4 (9%) patients receiving Soliris and 9 (21%) patients receiving placebo. The serious reactions included infections and progression of PNH. No deaths occurred in the study and no patients receiving Soliris experienced a thrombotic event; one thrombotic event occurred in a patient receiving placebo.

Among 193 patients with PNH treated with Soliris in the single arm, clinical study or the follow-up study, the adverse reactions were similar to those reported in the placebo-controlled clinical study. Serious adverse reactions occurred among 16% of the patients in these studies. The most common serious adverse reactions were: viral infection (2%), headache (2%), anemia (2%), and pyrexia (2%).

Immunogenicity

As with all proteins there is a potential for immunogenicity. Low titers of antibodies to Soliris were detected in 3/196 (2%) of all PNH patients treated with Soliris. No apparent correlation of antibody development to clinical response was observed. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to Soliris in an enzyme linked immunosorbent assay (ELISA) and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in the assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to Soliris with the incidence of antibodies to other products may be misleading.

Drug interaction studies have not been performed with Soliris.

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