FDA approves Soliris for the treatment of paroxysmal nocturnal hemoglobinuria

On March 16, 2007 the U.S. Food and Drug Administration granted approval to eculizumab injection (Soliris, Alexion Pharmaceuticals, Inc.) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.  Soliris is the first FDA-approved medication indicated for the treatment of any PNH manifestation.

In PNH, patients develop red blood cells (PNH cells) that are abnormally sensitive to complement.  The destruction and loss of these PNH cells (intravascular hemolysis) results in anemia, fatigue, difficulty in functioning, pain, dark urine, shortness of breath, and blood clots.  Soliris is a monoclonal antibody that inhibits the terminal components of complement, thereby reducing hemolysis.  The expanded number of circulating PNH cells increases the hemoglobin level.  Terminal complement inhibition with Soliris increases the susceptibility to serious meningococcal infections.

The safety and efficacy of Soliris were evaluated in a 26 week, double-blind, placebo-controlled clinical study of 87 PNH patients who had received at least four red blood cell transfusions over the past 12 months and had received meningococcal vaccination. Soliris was administered using the recommended dosage regimen described below.

The study showed significant improvements in hemoglobin stabilization and reduction in the number of transfused RBC units, the  study's co-primary endpoints (p < 0.01 for both endpoints).  Half the Soliris-treated patients, but none of the placebo-exposed patients achieved hemoglobin stabilization.  The median numbers of transfused RBC units were 10 units for placebo patients and 0 units for Soliris-treated patients.  Serious adverse reactions were similar between the study groups.  Non-serious adverse reactions reported at a higher rate among Soliris-treated patients included headache (44%), nasopharyngitis (23%), back pain (19%), nausea (16%), fatigue (12%) and cough (12%).  No severe or serious infusion reactions were reported.

PNH patients were also treated with Soliris in a single arm 52 week study and in a long term extension study.  In these longer term studies, patients showed improvements in measures of hemolysis similar to those observed in the randomized controlled trial.  In all PNH clinical studies of Soliris, meningococcal sepsis developed in two of the 196 patients receiving the drug.  Both had previously received meningococcal vaccination.  The Soliris prescribing information includes a boxed warning describing the risk for serious meningococcal infection and need for meningococcal vaccination.  Prior to beginning Soliris therapy, all patients and their prescribing physicians will be enrolled in a special risk management program that involves initial and continuing education and long term monitoring for detection of new safety findings.

The recommended Soliris dose regimen consists of 600 mg every seven days for the first four weeks, followed by 900 mg for the fifth dose seven days later, then 900 mg every 14 days thereafter.  Each dose is administered as an intravenous infusion over 35 minutes.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at
www.fda.gov/cder/foi/label/2007/125166lbl.pdf.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting Program via an online form at www.fda.gov/medwatch/report.htm , by faxing (1-800-FDA-0178) or mailing the postage-paid Form 3500 available at www.fda.gov/medwatch , or by telephone (1-800-FDA-1088).

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