Eculizumab improves symptoms for patients with paroxysmal nocturnal hemoglobinuria

At the end of treatment, nearly half in the eculizumab group had hemoglobin levels that remained above the previously transfused level.

Issue: November 1, 2006

Eculizumab is an effective therapy for paroxysmal nocturnal hemoglobinuria, according to results from a phase-3 trial.

“Eculizumab reduces intravascular hemolysis, reduces or eliminates the need for transfusion and improves anemia, fatigue and the quality of life in patients with PNH,” said lead researcher Peter Hillmen, MB, ChB, PhD, from the Leeds General Infirmary in England.

The reduction in intravascular hemolysis with eculizumab (Soloris, Alexion), as compared with placebo, was associated with a significant improvement in fatigue.

TRIUMPH study

Hillmen and colleagues evaluated the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein CF, in patients with PNH. CF inhibits terminal complement inactivation, according to a randomized, multicenter, double-blind, placebo-controlled study, the Transfusion Reduction Efficacy and Safety Clinical Investigation Using Eculizumab in Paroxysmal Nocturnal Hemoglobinuria (TRIUMPH).

In a preliminary 12-week, open-label clinical study involving 11 patients with PNH, eculizumab reduced intravascular hemolysis and the patients’ transfusion requirements.

In the TRIUMPH study, the researchers employed a two-week screening period, an observation period of up to three months and a 26-week treatment period. All eligible patients required four transfusions during the previous 12 months.

Hillmen and colleagues randomized 87 patients to receive either placebo (n=44) or eculizumab (n=43) within 10 days after the administration of transfusion. Patients received 600 mg of IV eculizumab or placebo every week for four weeks, followed by one week of eculizumab or placebo at a dose of 900 mg. They received a 900 mg maintenance dose of eculizumab or placebo every two weeks through week 26. Eighty-five patients completed the trial.

The two primary endpoints were the stabilization of hemoglobin levels and the number of units of packed red cells transfused during that period. Secondary endpoints included transfusion independence and improved fatigue. The researchers assessed all adverse events associated with treatment.

Outstanding outcomes

The effect of eculizumab or chronic intravascular hemolysis was demonstrated by an immediate and sustained decrease in lactate dehydrogenase levels through 26 weeks, compared with the placebo group (P<.001). This reduction led to an increase in PNH type III erythrocytes from a mean of 28.1% at baseline to 56.9% at 26 weeks (P<.001).

At the end of treatment, 49% of patients in the eculizumab group had hemoglobin levels that remained above the set point of 7.7 g/dL in the absence of transfusions. However, stabilization of hemoglobin levels did not occur in any patient in the placebo group (P<.001), according to the study.

After 26 weeks, the median number of units of packed red cells transfused per patient was zero in the eculizumab arm and 10 in the placebo arm (P<.001). Furthermore, the median time to the first transfusion was longer in the eculizumab arm than in the placebo arm (P<.001). Fifty-one percent of patients who received eculizumab achieved transfusion independence, compared with 0% in the placebo arm (P<.001).

Hillmen and colleagues observed that fatigue scores improved among patients in the eculizumab group, compared with the placebo group. No patients died during the study. The most common adverse events in the eculizumab group were headache, nasopharyngitis, back pain and nausea. Headache and back pain occurred more frequently in the eculizumab group than in the placebo group. There were nine serious adverse events in the placebo group, compared with four in the eculizumab group.

Alexion Pharmaceuticals funded the trial. – by Rebekah Cintolo

For more information:

Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233-1243.