FDA Okays Eculizumab (Soliris) for Paroxysmal Nocturnal Hemoglobinuria

ROCKVILLE, Md., March 19 -- The FDA has approved eculizumab (Soliris), the first of a new class of natural immune system blockers, for paroxysmal nocturnal hemoglobinuria, a rare blood disorder that can lead to disability and death.

The agency said that eculizumab does not cure paroxysmal nocturnal hemoglobinuria, but treats the breakdown of red blood cells, which is the most common characteristic of the disease. The drug blocks complement system activity, including the destruction of paroxysmal nocturnal hemoglobinuria red blood cells.

Steven Galson, M.D., M.P.H., director of the Center for Drug Evaluation and Research, said the approval"is important in that it offers a treatment other than blood transfusion that may help this small population of patients who are often very ill." The agent's was approval under the orphan drug program.

The FDA's approval hinged on the drug-maker's randomized, double-blind, placebo-controlled study of 87 patients with paroxysmal nocturnal hemoglobinuria plus other clinical studies.

The 26-week randomized study showed significant improvements in hemoglobin stabilization and reduction in the number of transfused red blood cell units, the study's co-primary endpoints (P

Half the eculizumab-treated patients, but none of the placebo-exposed patients, achieved hemoglobin stabilization. The median numbers of transfused red blood cell units were 10 units for placebo patients and 0 units for eculizumab-treated patients. Serious adverse reactions were similar between the groups. Non-serious adverse reactions reported at a higher rate among eculizumab-treated patients included headache (44%), nasopharyngitis (23%), back pain (19%), nausea (16%), fatigue (12%) and cough (12%). There were no severe or serious infusion reactions.

Paroxysmal noctural hemoglobinuria patients were also treated with eculizumab in a single arm 52-week study and in a long term extension study.

In these lengthier studies, patients showed improvements in measures of hemolysis similar to those in the randomized controlled trial.

In all of the paroxysmal nocturnal hemoglobinuria clinical studies of eculizumab, meningococcal sepsis developed in two of the 196 patients receiving the drug. Both had previously received meningococcal vaccination. The eculizumab-prescribing information includes a boxed warning describing the risk for serious meningococcal infection and need for meningococcal vaccination.

Prior to beginning eculizumab 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.

Paroxysmal nocturnal hemoglobinuria, which usually develops in adults, is a disease characterized by red blood cells that develop abnormally. Once the abnormal cells are present in the bloodstream, naturally occurring proteins (called the complement system) designed to destroy bacteria and other infection-causing organisms break these cells down. This leads to abnormally darkened urine and, more importantly, causes anemia.

Depending upon the severity of the disorder, patients with paroxysmal nocturnal hemoglobinuria may have pain, fatigue and debilitating weakness, the need for frequent blood transfusions, blood clots, and life-threatening or fatal strokes, heart attacks and intestinal disease.

Orphan drugs are developed to treat rare diseases or conditions that affect fewer than 200,000 patients in the United States. The Orphan Drug Act provides a seven-year period of exclusive marketing to the first manufacturer who obtains marketing approval for a designated orphan product. About one person out of a million people will be diagnosed with paroxysmal nocturnal hemoglobinuria.