Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening hematologic disease characterized by intravascular and extravascular hemolysis (IVH and EVH) mediated by effectors of the complement terminal and alternative pathways (TP and AP), respectively. Established therapies in the market include Alexion/AstraZeneca’s SOLIRIS (eculizumab) and ULTOMIRIS (ravulizumab), Novartis’ FABHALTA (iptacopan), Apellis’ EMPAVELI (pegcetacoplan), Astellas’ IZERVAY (avacincaptad pegol), and UCBs’ ZILBRYSQ (zilucoplan). 

A few of the potential emerging complement inhibitors are crovalimab (C5 inhibitor), nomacopan (C5/LTB4 inhibitor), CAN-106 (C5 inhibitor), ruxoprubart (Anti-Bb antibody), and KP104 (C5 and Factor H inhibitor).

Interim results from the Phase III COMMODORE 1 and COMMODORE 2 trials were presented at the EHA. For the primary analysis, 89 C5 inhibitor-experienced patients (Arm A: 45 patients; Arm B: 44 patients) were randomized in COMMODORE 1 and 204 C5 inhibitor-naïve-patients (Arm A: 135; Arm B: 69) were randomized in COMMODORE 2. The aim of the studies were to assess treatment preference using the treatment satisfaction and medication questionnaire-9 (TSQM-9) at Weeks 13 and 25 across both Arm A (crovalimab) and Arm B (eculizumab).

As of November 16, 2022, in the COMMODORE 1 trial, 85% of patients evaluated in the crovalimab group favored it over eculizumab. Among patients initially assigned to eculizumab who transitioned to crovalimab after 24 weeks, 96% in COMMODORE 1 and 84% in COMMODORE 2 preferred crovalimab. In the non-randomized arm of COMMODORE 1, 60% of those who switched from ravulizumab to crovalimab preferred crovalimab, citing similar reasons for their preference.

The top reasons for crovalimab preference were that the treatment required fewer hospital visits, was easier to administer, took less time to administer, and provided a better quality of life. 

KOL insights

“The preference for crovalimab was largely driven by increased convenience due to reduced treatment frequency. With every-4-weeks subcutaneous injection and the option for self-administration Crovalimab has the potential to offer a new treatment alternative for PNH  patients," MD, United States.

Conclusion 

PNH is a rare acquired disorder of the pluripotent hematopoietic stem cell. As per DelveInsight, in the United States, there are around 6,120 diagnosed prevalent cases. The only disease-modifying therapeutic strategies for PNH are complement inhibition therapies. Alexion/AstraZeneca’s SOLIRIS (eculizumab) was the first complement inhibitor approved in 2007 for paroxysmal nocturnal hemoglobinuria (PNH). Major players such as Kira (KP104), Ionis/Roche (RG6299), Alnylam (cemdisiran), Omeros (OMS906) and others are advancing their therapies through early and late-stage development

Crovalimab works by binding to C5, blocking the last step of the complement cascade, and is also recycled within the bloodstream, enabling rapid and sustained complement inhibition. Crovalimab’s recycling properties also enable low dose subcutaneous (SC) administration every four weeks. In addition, crovalimab binds to a different C5 binding site from current treatments, which has the potential to provide a treatment option for people with specific C5 gene mutations who do not respond to current therapies.

Initial findings from the Phase III studies showed that 84–96% of patients preferred crovalimab to eculizumab across the COMMODORE 1 and 2 trials. Absolute TSQM-9 scores for global satisfaction ranged from 71.0–79.1 and scores for perceived efficacy ranged from 73.2–77.7, surpassing those observed in the eculizumab arms.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to Paroxysmal nocturnal hemoglobinuria (PNH) - Market Insight, Epidemiology and Market Forecast – 2034, report.