NEW ORLEANS, La.—Vemircopan appears to prevent clinically significant extravascular hemolysis (EVH) and control intravascular hemolysis (IVH) in patients with paroxysmal nocturnal hemoglobinuria, according to an ongoing, phase 2, open-label study.

Absolute reticulocyte count declined from 212.4 x 103/uL to 120.0 x 103/uL, average hemoglobin went up from 7.9 g/dL to 11.9 g/dL, lactate dehydrogenase rapidly decreased by 81% from 7 × ULN to 1.4 × ULN, and a 13-point improvement in FACIT-Fatigue score was reported from baseline to week 12, reported Peter J. Browett, of the University of Auckland in New Zealand, and colleagues.  

Vemircopan is being developed as a monotherapy for PNH. The findings were presented here at the 64th ASH Annual Meeting and Exposition.

Read more about treatment for paroxysmal nocturnal hemoglobinuria

“PNH is a rare hematopoietic stem cell disorder characterized by the lack of complement inhibitory proteins on red blood cell surfaces. This deficit causes IVH, risk of thrombosis, and organ damage owing to uncontrolled terminal complement activation,” Browett said during the session.

“Treatment of patients with PNH with the C5 inhibitors eculizumab and ravulizumab has created improved clinical outcomes,” he added. “An estimated 10% to 20% of patients receiving C5 inhibitor treatment develop clinically significant EVH that may raise blood transfusions. Eculizumab does not compensate for CD55 deficiency associated with PNH; thus, patients may experience EVH due to the deposit of C3 fragments on the PNH red blood cells.”

The study team looked at patients with PNH and set out to evaluate the safety, efficacy,  pharmacokinetics, and pharmacodynamics of vemircopan monotherapy. The study has 3 extensions:  a 96-week long-term extension, a 12-week treatment period, and a 60-day screening period. Eculizumab switch, danicopan monotherapy rollover, and treatment-naïve were the 3 patient cohorts included in the study.

Here, the investigators present an interim analysis of these data highlighting the safety and efficacy information from the treatment-naïve cohort to evaluate proof of concept among patients with PNH. The analysis assessed 9 treatment-naïve patients. Mean age was 44.4 years, and males accounted for 63.% of the study cohort.

Study participants received 120 mg inhibition with twice-daily administration. Treatment was increased to 180 mg inhibition with twice-daily administration for select patients.

Notably, none of the participants needed a transfusion, with the exception of 1 patient as a result of low hemoglobin.

There were 31 treatment-emergent adverse events found across 9 patients, but roughly 80% were not due to the study treatment. Grade 3 treatment-emergent adverse events, serious treatment-emergent adverse events, deaths, and discontinuations were not reported among the study group.

Headaches were the most common treatment-emergent adverse events. Meningococcal infections, thrombotic events, and seizures were not reported in this study group.

“This interim efficacy and safety analysis provides proof of concept in PNH and suggests that phase 3 trials of vemircopan in patients with PNH are warranted,” Browett’s group concluded.


Browett PJ, et al. Vemircopan (ALXN2050) monotherapy in paroxysmal nocturnal hemoglobinuria: interim data from a phase 2 open-label proof-of-concept study. Poster presented at: 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA.