Pegcetacoplan Bests Eculizumab for PNH patients

Results from a phase III PEGASUS trial suggest that the pegcetacoplan inhibitor C3 improved hemoglobin levels better than eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) who remained anemic despite at least three months of eculizumab therapy. The data was released in December Meaningful meeting of the American Society of Hematology.

In this prohibition MedPage today video, study co-author Ilene C. Weitz, MD, of the Keck School of Medicine at the University of Southern California, talks about the results of the trial.

A transcript of her comments is:

The PEGASUS study was a study designed to examine the effect of C3 inhibition versus C5 inhibition in patients with PNH who already had C5 inhibition, but had a suboptimal response. The majority of these patients were transfusion-dependent and had hemoglobin <10.5 g / dL.

Therefore, the patients underwent overdose treatment and were then stratified to receive pegcetacoplan, the C3 inhibitor, against normal eculizumab. Ravu [ravulizumab] it was not considered in this group. And the patients were evaluated at 16 weeks, and the 16-week data, presented first at European hematology meetings, and then ASH, show an improvement of nearly four grams in hemoglobin in these patients. And there was an improvement in symptomatology as well.

So it seems that, like monotherapy, which is given subcutaneously two or three times a week, this was effective in stopping hemolysis in PNH patients that were intolerant to C5 inhibitor.

It offers an alternative to patients who are not getting the best response to a C5 inhibitor. There are still questions. Does it continue to stop thrombosis like a C5 inhibitor does? Strategies for evaluating progress are needed. And which patients are best for this treatment? We therefore have no information on patients who have a suboptimal response to C5, but who do not have severe anemia or are not dependent on transmission. And we know that all PNH patients appear to have some extravascular clearance on a C5 inhibitor.

So these are some of the issues that remain unresolved. We have not seen a large number of infections, which you would expect with a C3 protector. But all patients are vaccinated for everything and they were all on penicillin prophylaxis.