Rare Disease AdvisorRange of Clinical Trials Demonstrates an Improving Treatment Landscape in PNH

PNH Treatment Advances: A New Era of Oral Therapies and Dual Inhibition Strategies

The landscape of paroxysmal nocturnal hemoglobinuria (PNH) treatment is rapidly evolving, with a shift from intravenous to oral therapies and the emergence of dual inhibition strategies. Recent clinical trials presented at the 2023 American Society of Hematology (ASH) Annual Meeting highlight these advancements, offering new hope for patients and clinicians alike.

Key Points:

• Iptacopan (Fabhalta®), an orally administered drug by Novartis, has been approved by the FDA as a monotherapy for adults with PNH. The APPLY-PNH clinical trial showed sustained improvements in hemoglobin levels and high patient compliance.
• The ALPHA Trial evaluated danicopan, an oral factor D inhibitor, as an add-on treatment to ravulizumab or eculizumab. The results showed significant increases in hemoglobin levels without transfusion and avoided transfusion from week 12 to 24.
• The NCT05476887 Trial evaluated KP104, a fusion protein that combines a humanized anti-C5 monoclonal antibody with the functional domain of complement regulator factor H. The interim results showed positive clinical improvements across all patients.
• The COMMODORE Trials evaluated the effectiveness of crovalimab, a C5 antibody administered subcutaneously every 4 weeks. The trials showed that crovalimab has similar effectiveness to the existing marketed C5 inhibitors, with a similar safety profile.

Although the [ALPHA] trial was small, of short duration, with incomplete trial results, add-on danicopan to a C5 inhibitor appears to provide dual protection against intra- and extravascular hemolysis with continued protection against breakthrough hemolysis and thrombosis since a C5 inhibitor is continued. However, costs are a concern as this strategy would require 2 expensive medications.
— Anil Makam, MD, MAS, clinical researcher at the University of California San Francisco, and Foluso Agboola, MD, MPH, vice president of research at the Institute for Clinical and Economic Review, Boston, Massachusetts

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