New PNH case report shows anemia improved after treatment change
Patient’s symptoms eased after switch, with no safety issues reported
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The first clinical report of a patient with paroxysmal nocturnal hemoglobinuria (PNH) switching from PiaSky (crovalimab-akkz) to Fabhalta (iptacopan) was reported recently.
The patient in the report was a 72-year-old man who continued to experience PNH symptoms after an infection triggered worsening anemia while on PiaSky. After switching to Fabhalta, his symptoms eased considerably, and no breakthrough hemolysis or treatment-related adverse events were reported.
The case was described in the study, “Improvement in anemia and symptoms after switching from crovalimab to iptacopan in paroxysmal nocturnal hemoglobinuria,” published in Hematology.
Understanding PNH and limits of current treatments
PNH is a rare, acquired disease in which activation of the complement system — part of the immune system — leads to the destruction of red blood cells. This can cause anemia, or low levels of hemoglobin, leading to symptoms such as fatigue and shortness of breath.
PiaSky is an injection therapy designed to block the activity of a complement protein called C5. C5 inhibitors are effective at controlling intravascular hemolysis — blood cell destruction that occurs within blood vessels. However, they may be less effective at preventing extravascular hemolysis, or blood cell destruction outside of blood vessels. In some people with PNH, this can lead to ongoing anemia and symptoms despite treatment.
The man in this report had been diagnosed with PNH in 2008. In 2011, he started treatment with Soliris — the first approved PNH treatment, which, like PiaSky, blocks C5. He remained on Soliris for several years, then in 2023, he switched to PiaSky.
While he was taking PiaSky, his hemoglobin levels were “suboptimal,” researchers said, suggesting ongoing blood cell destruction outside of blood vessels. In late 2024, the man developed an infection that triggered a rapid worsening of anemia, which was clinically recognized as breakthrough hemolysis — uncontrolled blood cell destruction despite treatment. His lowest hemoglobin level during this episode was 7.6 g/dL — for context, the low end of normal for adult men is typically considered at least 13 g/dL.
The man’s infection resolved, but his anemia persisted, with hemoglobin levels remaining below 10 g/dL. He also reported symptoms including fatigue and shortness of breath.
Treatment switch considered after ongoing anemia and symptoms
Given these ongoing symptoms, the patient and his clinicians decided to switch from PiaSky to Fabhalta, an oral therapy that blocks a complement protein called factor B. Clinical trials have shown that Fabhalta can help reduce red blood cell destruction and improve hemoglobin levels and fatigue, so clinicians thought it might help relieve this patient’s symptoms given his ongoing disease activity despite PiaSky.
This is the first clinical report of such a treatment switch, so the man’s clinicians had to carefully plan how to manage the transition based on the known properties of each drug. PiaSky is given by injection every four weeks. Three weeks after his final injection, the man started Fabhalta at a dose of 200 mg twice daily. No breakthrough hemolysis or treatment-related adverse events were reported during follow-up, the researchers said.
Soon after switching therapies, the man’s hemoglobin levels increased, reaching 11.6 g/dL within about one to two weeks and remaining at or above 12 g/dL thereafter, with follow-up out to a year on Fabhalta. His shortness of breath resolved within about a week, and his fatigue improved within two weeks, researchers reported.
“This case represents the first clinical report of successful sequential therapy from the anti-C5 antibody [PiaSky] to the proximal complement inhibitor [Fabhalta]. Switching resulted in rapid and durable improvement in anemia and symptoms,” the scientists wrote.
PiaSky is sold by Genentech, and Fabhalta is sold by Novartis. No external funding was reported for the study; a grant from Tokai University in Japan supported the article’s submission fee, according to the authors.
