Studies Evaluate Anti-Complement Inhibitors for Treating Paroxysmal Nocturnal Hemoglobinuria

In the past, paroxysmal nocturnal hemoglobinuria (PNH) has been a devasting blood disorder characterized by red cell destruction, bone marrow failure and blood clots. The risk of thrombosis is particularly high and involves blood clots in vital organs like the liver or brain. Many patients also struggle with debilitating fatigue from profound anemia. Intravenous complement inhibitors have improved PNH care, but patients’ quality of life remain constrained by ongoing IV treatments.

Many hematologists will only encounter PNH once or twice in their practice. As a large referral center for PNH, Cleveland Clinic Cancer Institute has treated hundreds of patients with this disorder.

In addition to the previous contribution to pivotal trials of intravenous complement inhibitors in PNH, our center recently contributed patient data to two international phase 3 trials that led to FDA approval for the first-in class (anti-factor D) oral anti-complement inhibitor iptacopan. This drug is used as monotherapy in PNH and demonstrated equivalent if not better effects to the previously used anti-C5 therapy ..

Iptacopan was effective in alleviating intravascular symptoms but also extravascular hemolysis. The results of the studies, which were published in the New England Journal of Medicine, showed a robust response, including marked improvements in hematologic levels. In both trials, the majority of patients receiving iptacopan experienced an increase in their hemoglobin level of at least 2g per deciliter from their baseline, without reliance on a blood transfusion.

This new treatment option opens up potential therapeutic avenues for a broader spectrum of PNH patients, including those refractory to previous therapies In addition, having an oral medication offers greater ease of administration, particularly for children and for patients with poor veins.

“This treatment has the potential to move the standard of care forward, and improves the sense of normalcy for patients who previously relied on frequent infusions,” says Jaroslaw Maciejewski, MD, PhD, Chairman of the Department of Translational Hematology & Oncology Research at Taussig Cancer Institute. “When we consider ways to improve a patient’s quality of life, it’s not just alleviation of pain but reducing the need for medical intervention. Now there is the potential to improve responses, help patients feel better and alleviate the need for IV medication. Emotionally, that can be a big step forward for patients.”

Based on its long experience treating patients with PNH, Cleveland Clinic Cancer Institute was able to tap into its large cohort of patient data to better assess disease trajectory as well as anti-coagulation approaches. Clinical researchers recently published results of the real-world analysis of a very large cohort of these rare patients followed over an extended prior of time. “With the availability of these new therapies, the outlook and management of PNH has changed,” says Dr. Maciejewski. “Understanding real-world experiences is essential in the management of this disease.”

The results, which were reported in Blood, confirmed that the new class of anti-complement drugs used in PNH contribute to the alleviation of two main symptoms: anemia and thrombosis. This reduces the need for long-term anticoagulation therapy with traditional or novel blood thinners. As more patients are treated with anti-complement inhibitors, the center will continue to analyze symptomology, response rates and duration of response.